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Review

Vaccines against gastroenteritis, current progress and challenges

, &
Pages 1486-1517 | Received 23 Dec 2019, Accepted 12 May 2020, Published online: 18 Jun 2020

References

  • Black RE, Cousens S, Johnson HL, Lawn JE, Rudan I, Bassani DG, Jha P, Campbell H, Walker CF, Cibulskis R, et al. Global, regional, and national causes of child mortality in 2008: a systematic analysis. Lancet. 2010;375(9730):1969–1987. doi:10.1016/S0140-6736(10)60549-1.
  • Kotloff KL, Nataro JP, Blackwelder WC, Nasrin D, Farag TH, Panchalingam S, Wu Y, Sow SO, Sur D, Breiman RF, et al. Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study. Lancet. 2013;382(9888):209–222. doi:10.1016/S0140-6736(13)60844-2.
  • Kirk MD, Pires SM, Black RE, Caipo M, Crump JA, Devleesschauwer B, Dopfer D, Fazil A, Fischer-Walker CL, Hald T, et al. World Health Organization Estimates of the Global and Regional Disease Burden of 22 Foodborne Bacterial, Protozoal, and Viral Diseases, 2010: A Data Synthesis. PLoS Med. 2015;12(12):e1001921. doi:10.1371/journal.pmed.1001921.
  • Vos T, Allen C, Arora M, Barber RM, Bhutta ZA, Brown A, Carter A, Casey DC, Charlson FJ, Chen AZ. GBD 2015. Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the global burden of disease study 2015. Lancet. 2016;388(10053):1545–1602. doi:10.1016/S0140-6736(16)31678-6.
  • Troeger C, Blacker BF, Khalil IA, Rao PC, Cao SJ, Zimsen SRM, Albertson S, Stanaway JD, Deshpande A, Brown A, et al. Estimates of the global, regional, and national morbidity, mortality, and aetiologies of diarrhoea in 195 countries: a systematic analysis for the global burden of disease study 2016. Lancet Infect Dis. 2018;18(11):1211–1228. doi:10.1016/S1473-3099(18)30362-1.
  • Platts-Mills JA, Babji S, Bodhidatta L, Gratz J, Haque R, Havt A, McCormick B, McGrath M, Olortegui M, Samie A, et al. Pathogen-specific burdens of community diarrhoea in developing countries: a multisite birth cohort study (MAL-ED). Lancet Glob Health. 2015;3(9):e564–575. doi:10.1016/S2214-109X(15)00151-5.
  • World Health Organization. Rotavirus vaccines. Wkly Epidemiol Rec. 2007;82(32):285–295.
  • Bernstein DI, Glass RI, Rodgers G, Davidson BL, Sack DA. Evaluation of rhesus rotavirus monovalent and tetravalent reassortant vaccines in US children. JAMA. 1995;273(15):1191–1196. doi:10.1001/jama.1995.03520390051032.
  • Joensuu J, Koskenniemi E, Pang XL, Vesikari T. Randomised placebo-controlled trial of rhesus-human reassortant rotavirus vaccine for prevention of severe rotavirus gastroenteritis. Lancet. 1997;350(9086):1205–1209. doi:10.1016/S0140-6736(97)05118-0.
  • PerezSchael I, Guntinas MJ, Perez M, Pagone V, Rojas AM, Gonzalez R, Cunto W, Hoshino Y, Kapikian AZ. Efficacy of the rhesus rotavirus-based quadrivalent vaccine in infants and young children in Venezuela. N Engl J Med. 1997;337(17):1181–1187. doi:10.1056/NEJM199710233371701.
  • Rennels M, Glass R, Dennehy P, Bernstein D, Pichichero M, Zito E, Mack M, Davidson B, Kapikian A. Safety and efficacy of high-dose rhesus-human reassortant rotavirus vaccines - report of the national multicenter trial. Pediatrics. 1996;97(1):7–13. United States Rotavirus Vaccine Efficacy Group
  • Santosham M, Moulton LH, Reid R, Croll J, Weatherbolt R, Ward R, Forro J, Zito E, Mack M, Brenneman G, et al. Efficacy and safety of high-dose rhesus-human reassortant rotavirus vaccine in Native American populations. J Pediatr. 1997;131(4):632–638. doi:10.1016/S0022-3476(97)70076-3.
  • Banyai K, Laszlo B, Duque J, Steele AD, Nelson EAS, Gentsch JR, Parashar UD. Systematic review of regional and temporal trends in global rotavirus strain diversity in the pre rotavirus vaccine era: insights for understanding the impact of rotavirus vaccination programs. Vaccine. 2012;30S:A122–A130. doi:10.1016/j.vaccine.2011.09.111.
  • Doro R, Laszlo B, Martella V, Leshem E, Gentsch J, Parashar U, Banyai K. Review of global rotavirus strain prevalence data from six years post vaccine licensure surveillance: is there evidence of strain selection from vaccine pressure? Infect Genet Evol. 2014;28:446–461. doi:10.1016/j.meegid.2014.08.017.
  • Parashar UD, Nelson EAS, Kang G. Diagnosis, management, and prevention of rotavirus gastroenteritis in children. BMJ. 2013;347:f7204.
  • Murphy TV, Gargiullo PM, Massoudi MS, Nelson DB, Jumaan AO, Okoro CA, Zanardi LR, Setia S, Fair E, LeBaron CW, et al. Intussusception among infants given an oral rotavirus vaccine. N Engl J Med. 2001;344(8):564–572. doi:10.1056/NEJM200102223440804.
  • Centers for Disease Control and Prevention. NMA recommends withdrawal of rotavirus vaccine. J Natl Med Assoc 1999;91:645.
  • Rothman KJ, Young-Xu Y, Arellano F. Age dependence of the relation between reassortant rotavirus vaccine (RotaShield) and intussusception. J Infect Dis. 2006;193(6):898. doi:10.1086/500217.
  • Armah GE, Kapikian AZ, Vesikari T, Cunliffe N, Jacobson RM, Burlington DB, Ruiz LP. Efficacy, immunogenicity, and safety of two doses of a tetravalent rotavirus vaccine rrv-tv in ghana with the first dose administered during the neonatal period. J Infect Dis. 2013;208(3):423–431. doi:10.1093/infdis/jit174.
  • Ciarlet M, Schodel F. Development of a rotavirus vaccine: clinical safety, immunogenicity, and efficacy of the pentavalent rotavirus vaccine, rotateq®. Vaccine. 2009;27S:G72–G81. doi:10.1016/j.vaccine.2009.09.107.
  • Block SL, Vesikari T, Goveia MG, Rivers SB, Adeyi BA, Dallas MJ, Bauder J, Boslego JW, Heaton PM. Efficacy, immunogenicity, and safety of a pentavalent human-bovine (WC3) reassortant rotavirus vaccine at the end of shelf life. Pediatrics. 2007;119(1):11–18. doi:10.1542/peds.2006-2058.
  • Vesikari T, Clark HF, Offit P, Schodel F, Dallas M, Heaton P, Krah D, Shaw A, Garbarg-Chenon A, Golm G, et al. The effect of dose and composition of a pentavalent rotavirus reassortant vaccine (rotaTeqTM) upon safety, efficacy, and immunogenicity in healthy infants. Presented at: The 37th National Immunization Conference of CDC. 2003 Mar 19; Ontario, Canada.
  • Clark HF, Bernstein DI, Dennehy PH, Offit P, Pichichero M, Treanor J, Ward RL, Krah DL, Shaw A, Dallas MJ, et al. Safety, efficacy, and immunogenicity of a live, quadrivalent human-bovine reassortant rotavirus vaccine in healthy infants. J Pediatr. 2004;144(2):184–190. doi:10.1016/j.jpeds.2003.10.054.
  • Soares-Weiser K, MacLehose H, Bergman H, Ben-Aharon I, Nagpal S, Goldberg E, Pitan F, Cunliffe N. Vaccines for preventing rotavirus diarrhoea: vaccines in use. Cochrane Database Syst Rev. 2012;2:CD008521.
  • Tate JE, Patel MM, Cortese MM, Lopman BA, Gentsch JR, Fleming J, Steele AD, Parashar UD. Remaining issues and challenges for rotavirus vaccine in preventing global childhood diarrheal morbidity and mortality. Expert Rev Vaccines. 2012;11(2):211–220. doi:10.1586/erv.11.184.
  • Patel M, Pedreira C, De Oliveira LH, Umana J, Tate J, Lopman B, Sanchez E, Reyes M, Mercado J, Gonzalez A, et al. Duration of protection of pentavalent rotavirus vaccination in Nicaragua. Pediatrics. 2012;130(2):E365–E372. doi:10.1542/peds.2011-3478.
  • Bernstein DI, Sack DA, Rothstein E, Reisinger K, Smith VE, O’Sullivan D, Spriggs DR, Ward RL. Efficacy of live, attenuated, human rotavirus vaccine 89-12 in infants: a randomised placebo-controlled trial. Lancet. 1999;354(9175):287–290. doi:10.1016/S0140-6736(98)12106-2.
  • Vesikari T, Karvonen A, Puustinen L, Zeng SQ, Szakal ED, Delem A, De Vos B. Efficacy of RIX4414 live attenuated human rotavirus vaccine in Finnish infants. Pediatr Infect Dis J. 2004;23(10):937–943. doi:10.1097/01.inf.0000141722.10130.50.
  • Araujo EC, ClemenS SAC, Oliveira CS, Justino MCA, Rubio P, Gabbay YB, da Silva VB, Mascarenhas JDP, Noronha VL, Clemens R, et al. Safety, immunogenicity, and protective efficacy of two doses of RIX4414 live attenuated human rotavirus vaccine in healthy Brazilian infants. J Pediatr (Rio J). 2007;83(3):217–224. doi:10.2223/JPED.1600.
  • Perez-Schael I, Salinas B, Tomat M, Linhares AC, Guerrero ML, Ruiz-Palacios GM, Bouckenooghe A, Yarzabal JP. Efficacy of the human rotavirus vaccine RIX4414 in malnourished children. J Infect Dis. 2007;196(4):537–540. doi:10.1086/519687.
  • Vesikari T, Karvonen A, Prymula R, Schuster V, Tejedor JC, Cohen R, Meurice F, Han HH, Damaso S, Bouckenooghe A. Efficacy of human rotavirus vaccine against rotavirus gastroenteritis during the first 2 years of life in European infants: randomised, double-blind controlled study. Lancet. 2007;370(9601):1757–1763. doi:10.1016/S0140-6736(07)61744-9.
  • Linhares AC, Velazquez FR, Perez-Schael I, Saez-Llorens X, Abate H, Espinoza F, Lopez P, Macias-Parra M, Ortega-Barria E, Rivera-Medina DM, et al. Efficacy and safety of an oral live attenuated human rotavirus vaccine against rotavirus gastroenteritis during the first 2 years of life in Latin American infants: a randomised, double-blind, placebo-controlled phase III study. Lancet. 2008;371(9619):1181–1189. doi:10.1016/S0140-6736(08)60524-3.
  • O’Ryan M, Linhares AC. Update on rotarix: an oral human rotavirus vaccine. Expert Rev Vaccines. 2009;8(12):1627–1641. doi:10.1586/erv.09.136.
  • Kawamura N, Tokoeda Y, Oshima M, Okahata H, Tsutsumi H, Van Doorn LJ, Muto H, Smolenov I, Suryakiran PV, Han HH. Efficacy, safety and immunogenicity of RIX4414 in Japanese infants during the first two years of life. Vaccine. 2011;29(37):6335–6341. doi:10.1016/j.vaccine.2011.05.017.
  • Cunliffe NA, Witte D, Ngwira BM, Todd S, Bostock NJ, Turner AM, Chimpeni P, Victor JC, Steele AD, Bouckenooghe A, et al. Efficacy of human rotavirus vaccine against severe gastroenteritis in Malawian children in the first two years of life: A randomized, double-blind, placebo controlled trial. Vaccine. 2012;30:A36–A43. doi:10.1016/j.vaccine.2011.09.120.
  • Madhi SA, Kirsten M, Louw C, Bos P, Aspinall S, Bouckenooghe A, Neuzil KM, Steele AD. Efficacy and immunogenicity of two or three dose rotavirus-vaccine regimen in South African children over two consecutive rotavirus-seasons: A randomized, double-blind, placebo-controlled trial. Vaccine. 2012;30:A44–A51. doi:10.1016/j.vaccine.2011.08.080.
  • Phua KB, Lim FS, Lau YL, Nelson EAS, Huang LM, Quak SH, Lee BW, van Doorn LJ, Teoh YL, Tang H, et al. Rotavirus vaccine RIX4414 efficacy sustained during the third year of life: A randomized clinical trial in an Asian population. Vaccine. 2012;30(30):4552–4557. doi:10.1016/j.vaccine.2012.03.030.
  • Lau YL, Nelson EAS, Poon KH, Chan PKS, Chiu S, Sung R, Leung CW, Ng D, Ma YM, Chan D, et al. Efficacy, safety and immunogenicity of a human rotavirus vaccine (RIX4414) in Hong Kong children up to three years of age: A randomized, controlled trial. Vaccine. 2013;31(18):2253–2259. doi:10.1016/j.vaccine.2013.03.001.
  • Li RC, Huang T, Li YP, Luo D, Tao JH, Fu BT, Si GA, Nong Y, Mo ZH, Liao XY, et al. Human rotavirus vaccine (RIX4414) efficacy in the first two years of life A randomized, placebo-controlled trial in China. Hum Vacc Immunother. 2014;10(1):11–18. doi:10.4161/hv.26319.
  • Phua KB, Lim FS, Quak SH, Lee BW, Teoh YL, Suryakiran PV, Han HH, Bock HL. Efficacy, immunogenicity and safety of a human rotavirus vaccine rix4414 in Singaporean Infants. Ann Acad Med Singapore. 2016;45:44–50.
  • Willame C, Noordegraaf-Schouten MV, Gvozdenovic E, Kochems K, Oordt-Speets A, Praet N, van Hoorn R, Rosillon D. effectiveness of the oral human attenuated rotavirus vaccine: a systematic review and meta-analysis-2006-2016. Open Forum Infect Di. 2018;5:ofy292.
  • Luna-Casas G, Juliao P, Carreno-Manjarrez R, Castaneda-Prado A, Cervantes-Apolinar MY, Navarro-Rodriguez R, Sanchez-Gonzalez G, Cortes-Alcala R, DeAntonio R. Vaccine coverage and compliance in Mexico with the two-dose and three-dose rotavirus vaccines. Hum Vaccin Immunother. 2019;15(6):1251–1259. doi:10.1080/21645515.2018.1540827.
  • Clark A, van Zandvoort K, Flasche S, Sanderson C, Bines J, Tate J, Parashar U, Jit M. Efficacy of live oral rotavirus vaccines by duration of follow-up: a meta-regression of randomised controlled trials. Lancet Infect Dis. 2019;19(7):717–727. doi:10.1016/S1473-3099(19)30126-4.
  • Bhandari N, Sharma P, Glass RI, Ray P, Greenberg H, Taneja S, Saksena M, Rao CD, Gentsch JR, Parashar U, et al. Safety and immunogenicity of two live attenuated human rotavirus vaccine candidates, 116E and I321, in infants: results of a randomised controlled trial. Vaccine. 2006;24(31–32):5817–5823. doi:10.1016/j.vaccine.2006.05.001.
  • Bhandari N, Sharma P, Taneja S, Kumar T, Rongsen-Chandola T, Appaiahgari MB, Mishra A, Singh S, Vrati S, Grp RVD. A Dose-Escalation Safety and Immunogenicity Study of Live Attenuated Oral Rotavirus Vaccine 116E in Infants: A Randomized, Double-Blind, Placebo-Controlled Trial. J Infect Dis. 2009;200(3):421–429. doi:10.1086/600104.
  • Bhandari N, Rongsen-Chandola T, Bavdekar A, John J, Antony K, Taneja S, Goyal N, Kawade A, Kang G, Rathore SS, et al. Efficacy of a monovalent human-bovine (116E) rotavirus vaccine in Indian infants: a randomised, double-blind, placebo-controlled trial. Lancet. 2014;383(9935):2136–2143. doi:10.1016/S0140-6736(13)62630-6.
  • Bhandari N, Rongsen-Chandola T, Bavdekar A, John J, Antony K, Taneja S, Goyal N, Kawade A, Kang G, Rathore SS, et al. Efficacy of a monovalent human-bovine (116E) rotavirus vaccine in Indian children in the second year of life. Vaccine. 2014;32:A110–A116. doi:10.1016/j.vaccine.2014.04.079.
  • Ella R, Babji S, Ciarlet M, Blackwelder WC, Vadrevu KM. A randomized, open-labelled, non-inferiority phase 4 clinical trial to evaluate the immunogenicity and safety of the live, attenuated, oral rotavirus vaccine, ROTAVAC® in comparison with a licensed rotavirus vaccine in healthy infants. Vaccine. 2019;37(31):4407–4413. doi:10.1016/j.vaccine.2019.05.069.
  • Luna EJA, Frazatti-Gallina NM, Timenetsky MCST, Cardoso MRA, Veras MASM, Miraglia JL, Escobar AMU, Grisi SJFE, Raw I, Precioso AR. A phase I clinical trial of a new 5-valent rotavirus vaccine. Vaccine. 2013;31(7):1100–1105. doi:10.1016/j.vaccine.2012.12.020.
  • Desai S, Rathi N, Kawad A, Venkatramanan P, Kundu R, Laiwani SK, Dubey AP, Rao JV, Narayanappa D, Ghildiyal R, et al. Non-interference of Bovine-Human reassortant pentavalent rotavirus vaccine ROTASIIL® with the immunogenicity of infant vaccines in comparison with a licensed rotavirus vaccine. Vaccine. 2018;36(37):5519–5523. doi:10.1016/j.vaccine.2018.07.064.
  • Kawade A, Babji S, Kamath V, Raut A, Kumar CM, Kundu R, Venkatramanan P, Lalwani SK, Bavdekar A, Juvekar S, et al. Immunogenicity and lot-to-lot consistency of a ready to use liquid bovine-human reassortant pentavalent rotavirus vaccine (ROTASIIL - Liquid) in Indian infants. Vaccine. 2019;37(19):2554–2560. doi:10.1016/j.vaccine.2019.03.067.
  • Kulkarni PS, Desai S, Tewari T, Kawade A, Goyal N, Garg BS, Kumar D, Kanungo S, Kamat V, Kang G, et al. A randomized Phase III clinical trial to assess the efficacy of a bovine-human reassortant pentavalent rotavirus vaccine in Indian infants. Vaccine. 2017;35(45):6228–6237. doi:10.1016/j.vaccine.2017.09.014.
  • Fu CX, Wang M, Liang JH, He TJ, Wang DH, Xu JX. Effectiveness of Lanzhou lamb rotavirus vaccine against rotavirus gastroenteritis requiring hospitalization: A matched case-control study. Vaccine. 2007;25(52):8756–8761. doi:10.1016/j.vaccine.2007.10.036.
  • Fu CX, Tate JE, Jiang BM. Effectiveness of Lanzhou lamb rotavirus vaccine against hospitalized gastroenteritis Further analysis and update. Hum Vaccin. 2010;6(11):953. doi:10.4161/hv.6.11.12847.
  • Fu CX, He Q, Xu JX, Xie HP, Ding P, Hu WS, Dong ZQ, Liu XY, Wang M. Effectiveness of the lanzhou lamb rotavirus vaccine against gastroenteritis among children. Vaccine. 2012;31(1):154–158. doi:10.1016/j.vaccine.2012.10.078.
  • Li J, Zhang Y, Yang Y, Liang ZC, Tian Y, Liu BW, Gao ZY, Jia L, Chen LJ, Wang QY. Effectiveness of Lanzhou lamb rotavirus vaccine in preventing gastroenteritis among children younger than 5 years of age. Vaccine. 2019;37:3611–3616.
  • Le LT, Nguyen TV, Nguyen PM, Huong NT, Huong NT, Huong NTM, Hanh TB, Ha DN, Anh DD, Gentsch JR, et al. Development and characterization of candidate rotavirus vaccine strains derived from children with diarrhoea in Vietnam. Vaccine. 2009;27:F130–F138. doi:10.1016/j.vaccine.2009.08.086.
  • Anh DD, Trang NV, Thiem VD, Nguyen THA, Mao ND, Wang YH, Jiang BM, Hien ND, Luan LT, Grp R-MVT. A dose-escalation safety and immunogenicity study of a new live attenuated human rotavirus vaccine (Rotavin-M1) in Vietnamese children. Vaccine. 2012;30:A114–A121. doi:10.1016/j.vaccine.2011.07.118.
  • Groome MJ, Koen A, Fix A, Page N, Jose L, Madhi SA, McNeal M, Dally L, Cho I, Power M, et al. Safety and immunogenicity of a parenteral P2-VP8-P[8] subunit rotavirus vaccine in toddlers and infants in South Africa: a randomised, double-blind, placebo-controlled trial. Lancet Infect Dis. 2017;17(8):843–853. doi:10.1016/S1473-3099(17)30242-6.
  • Groome MJ, Fairlie L, Morrison J, Fix A, Koen A, Masenya M, Page N, Jose L, Madhi SA, McNeal M, et al. Safety and Immunogenicity of a parenteral P2-VP8 subunit rotavirus vaccine. Presented at: The 13th International Rotavirus Symposium; 2018 Aug 29-31; Minsk, Belarus.
  • Burke RM, Tate JE, Kirkwood CD, Steele AD, Parashar UD. Current and new rotavirus vaccines. Curr Opin Infect Dis. 2019;32(5):435–444. doi:10.1097/QCO.0000000000000572.
  • Glass RI, Noel J, Ando T, Fankhauser R, Belliot G, Mounts A, Parashar UD, Bresee JS, Monroe SS. The epidemiology of enteric caliciviruses from humans: A reassessment using new diagnostics. J Infect Dis. 2000;181(s2):S254–S261. doi:10.1086/315588.
  • Koopmans M, Vinje J, de Wit M, Leenen I, van der Poel W, van Duynhoven Y. Molecular epidemiology of human enteric caliciviruses in The Netherlands. J Infect Dis. 2000;181(s2):S262–S269. doi:10.1086/315573.
  • Dolin R. Perspective: noroviruses - Challenges to control. N Engl J Med. 2007;357(11):1072–1073. doi:10.1056/NEJMp078050.
  • Hall AJ, Lopman BA, Payne DC, Patel MM, Gastanaduy PA, Vinje J, Parashar UD. Norovirus disease in the United States. Emerg Infect Dis. 2013;19(8):1198–1205. doi:10.3201/eid1908.130465.
  • Kroneman A, Vega E, Vennema H, Vinje J, White PA, Hansman G, Green K, Martella V, Katayama K, Koopmans M. Proposal for a unified norovirus nomenclature and genotyping. Arch Virol. 2013;158(10):2059–2068. doi:10.1007/s00705-013-1708-5.
  • Cortes-Penfield NW, Ramani S, Estes MK, Atmar RL. Prospects and Challenges in the development of a Norovirus Vaccine. Clin Ther. 2017;39(8):1537–1549. doi:10.1016/j.clinthera.2017.07.002.
  • Tran TNH, Trainor E, Nakagomi T, Cunliffe NA, Nakagomi O. Molecular epidemiology of noroviruses associated with acute sporadic gastroenteritis in children: global distribution of genogroups, genotypes and GII.4variants. J Clin Virol. 2013;56(3):185–193. doi:10.1016/j.jcv.2012.11.011.
  • Ball JM, Graham DY, Opekun AR, Gilger MA, Guerrero RA, Estes MK. Recombinant Norwalk virus-like particles given orally to volunteers: phase I study. Gastroenterology. 1999;117(1):40–48. doi:10.1016/S0016-5085(99)70548-2.
  • El-Kamary SS, Pasetti MF, Mendelman PM, Frey SE, Bernstein DI, Treanor JJ, Ferreira J, Chen WH, Sublett R, Richardson C, et al. Adjuvanted intranasal norwalk virus-like particle vaccine elicits antibodies and antibody-secreting cells that express homing receptors for mucosal and peripheral lymphoid tissues. J Infect Dis. 2010;202(11):1649–1658. doi:10.1086/657087.
  • Ramirez K, Wahid R, Richardson C, Bargatze RF, El-Kamary SS, Sztein MB, Pasetti MF. Intranasal vaccination with an adjuvanted Norwalk virus-like particle vaccine elicits antigen-specific B memory responses in human adult volunteers. Clin Immunol. 2012;144(2):98–108. doi:10.1016/j.clim.2012.05.006.
  • Parra GI, Bok K, Taylor R, Haynes JR, Sosnovtsev SV, Richardson C, Green KY. Immunogenicity and specificity of norovirus Consensus GII.4 virus-like particles in monovalent and bivalent vaccine formulations. Vaccine. 2012;30(24):3580–3586. doi:10.1016/j.vaccine.2012.03.050.
  • Treanor JJ, Atmar RL, Frey SE, Gormley R, Chen WH, Ferreira J, Goodwin R, Borkowski A, Clemens R, Mendelman PM. A Novel intramuscular bivalent norovirus virus-like particle vaccine candidate-reactogenicity, safety, and immunogenicity in a phase 1 trial in healthy adults. J Infect Dis. 2014;210(11):1763–1771. doi:10.1093/infdis/jiu337.
  • Sundararajan A, Sangster MY, Frey S, Atmar RL, Chen WH, Ferreira J, Bargatze R, Mendelman PM, Treanor JJ, Topham DJ. Robust mucosal-homing antibody-secreting B cell responses induced by intramuscular administration of adjuvanted bivalent human norovirus-like particle vaccine. Vaccine. 2015;33(4):568–576. doi:10.1016/j.vaccine.2014.09.073.
  • Ramani S, Neill FH, Ferreira J, Treanor JJ, Frey SE, Topham DJ, Goodwin RR, Borkowski A, Baehner F, Mendelman PM, et al. B-cell responses to intramuscular administration of a bivalent virus-like particle Human Norovirus Vaccine. Clin Vaccine Immunol. 2017;24(5):e00571–16. doi:10.1128/CVI.00571-16.
  • Bernstein DI, Atmar RL, Lyon GM, Treanor JJ, Chen WH, Jiang X, Vinje J, Gregoricus N, Frenck RW, Moe CL, et al. Norovirus vaccine against experimental human gii.4 virus illness: a challenge study in healthy adults. J Infect Dis. 2015;211(6):870–878. doi:10.1093/infdis/jiu497.
  • Blazevic V, Lappalainen S, Nurminen K, Huhti L, Vesikari T. Norovirus VLPs and rotavirus VP6 protein as combined vaccine for childhood gastroenteritis. Vaccine. 2011;29(45):8126–8133. doi:10.1016/j.vaccine.2011.08.026.
  • Tamminen K, Lappalainen S, Huhti L, Vesikari T, Blazevic V. Trivalent combination vaccine induces broad heterologous immune responses to norovirus and rotavirus in mice. PLoS One. 2013;8(7):e70409. doi:10.1371/journal.pone.0070409.
  • Tan M, Jiang X. The P domain of norovirus capsid protein forms a subviral particle that binds to histo-blood group antigen receptors. J Virol. 2005;79(22):14017–14030. doi:10.1128/JVI.79.22.14017-14030.2005.
  • Fang H, Tan M, Xia M, Wang LH, Jiang X. Norovirus P Particle efficiently elicits innate, humoral and cellular immunity. PLoS One. 2013;8(4):e63269. doi:10.1371/journal.pone.0063269.
  • Baric RS, Yount B, Lindesmith L, Harrington PR, Greene SR, Tseng FC, Davis N, Johnston RE, Klapper DG, Moe CL. Expression and self-assembly of norwalk virus capsid protein from venezuelan equine encephalitis virus replicons. J Virol. 2002;76(6):3023–3030. doi:10.1128/JVI.76.6.3023-3030.2002.
  • Guo L, Wang JW, Zhou HL, Si HL, Wang M, Song JD, Han BJ, Shu Y, Ren LL, Qu J, et al. Intranasal administration of a recombinant adenovirus expressing the norovirus capsid protein stimulates specific humoral, mucosal, and cellular immune responses in mice. Vaccine. 2008;26(4):460–468. doi:10.1016/j.vaccine.2007.11.039.
  • Ramani S, Estes MK, Atmar RL. Norovirus vaccine development. In: Viral Gastroenteritis. MA: Academic Press; 2016. p. 447–469.
  • Hansman GS, Natori K, Shirato-Horikoshi H, Ogawa S, Oka T, Katayama K, Tanaka T, Miyoshi T, Sakae K, Kobayashi S, et al. Genetic and antigenic diversity among noroviruses. J Gen Virol. 2006;87(4):909–919. doi:10.1099/vir.0.81532-0.
  • Parrino TA, Schreiber DS, Trier JS, Kapikian AZ, Blacklow NR. Clinical immunity in acute gastroenteritis caused by norwalk agent. N Engl J Med. 1977;297(2):86–89. doi:10.1056/NEJM197707142970204.
  • Cukor G, Nowak NA, Blacklow NR. Immunoglobulin-m responses to the norwalk virus of gastroenteritis. Infect Immun. 1982;37(2):463–468. doi:10.1128/IAI.37.2.463-468.1982.
  • Johnson PC, Mathewson JJ, Dupont HL, Greenberg HB. Multiple-challenge study of host susceptibility to norwalk gastroenteritis in United-States Adults. J Infect Dis. 1990;161(1):18–21. doi:10.1093/infdis/161.1.18.
  • Lindesmith L, Moe C, Marionneau S, Ruvoen N, Jiang X, Lindbland L, Stewart P, LePendu J, Baric R. Human susceptibility and resistance to Norwalk virus infection. Nat Med. 2003;9(5):548–553. doi:10.1038/nm860.
  • Simmons K, Gambhir M, Leon J, Lopman B. Duration of Immunity to Norovirus Gastroenteritis. Emerg Infect Dis. 2013;19(8):1260–1267. doi:10.3201/eid1908.130472.
  • Reeck A, Kavanagh O, Estes MK, Opekun AR, Gilger MA, Graham DY, Atmar RL. Serological correlate of protection against norovirus-induced gastroenteritis. J Infect Dis. 2010;202(8):1212–1218. doi:10.1086/656364.
  • Atmar RL, Bernstein DI, Lyon GM, Treanor JJ, Al-Ibrahim MS, Graham DY, Vinje J, Jiang X, Gregoricus N, Frenck RW, et al. Serological correlates of protection against a gii.4 norovirus. Clin Vaccine Immunol. 2015;22(8):923–929. doi:10.1128/CVI.00196-15.
  • Ramani S, Estes MK, Atmar RL. Correlates of protection against norovirus infection and disease-where are we now, where do we go? PLoS Pathog. 2016;12(4):e1005334. doi:10.1371/journal.ppat.1005334.
  • Xia M, Wei C, Wang L, Cao D, Meng XJ, Jiang X, Tan M. A trivalent vaccine candidate against hepatitis E virus, norovirus, and astrovirus. Vaccine. 2016;34(7):905–913. doi:10.1016/j.vaccine.2015.12.068.
  • Bidokhti MRM, Ullman K, Hammer AS, Jensen TH, Chriel M, Byrareddy SN, Baule C. Immunogenicity and efficacy evaluation of subunit astrovirus vaccines. Vaccines (Basel). 2019;7(3):79. doi:10.3390/vaccines7030079.
  • Raqib R, Mia SMS, Qadri F, Alam TI, Alam NH, Chowdhury AK, Mathan MM, Andersson J. Innate immune responses in children and adults with shigellosis. Infect Immun. 2000;68(6] has been updated. OK?):3620–3629. doi:10.1128/IAI.68.6.3620-3629.2000.
  • TranVan Nhieu G, Sansonetti P. The cellular microbiology of Shigella invasion of epithelial cells. In: William D, Picking WLP, editors. Shigella: molecular and cellular biology. Lawrence (KS): Caister Academic Press; 2015. p. 151–168.
  • Scheiring J, Andreoli SP, Zimmerhackl LB. Treatment and outcome of shiga-toxin-associated hemolytic uremic syndrome (HUS). Pediatr Nephrol. 2008;23(10):1749–1760. doi:10.1007/s00467-008-0935-6.
  • Dupont HL, Levine MM, Hornick RB, Formal SB. Inoculum size in shigellosis and Implications for expected mode of transmission. J Infect Dis. 1989;159(6):1126–1128. doi:10.1093/infdis/159.6.1126.
  • Cohen D, Green M, Block C, Slepon R, Ambar R, Wasserman SS, Levine MM. Reduction of transmission of shigellosis by control of houseflies (Musca-Domestica). Lancet. 1991;337:993–997.
  • Farag TH, Faruque AS, Wu Y, Das SK, Hossain A, Ahmed S, Ahmed D, Nasrin D, Kotloff KL, Panchilangam S, et al. Housefly population density correlates with shigellosis among children in Mirzapur, Bangladesh: a time series analysis. PLoS Negl Trop Dis. 2013;7:e2280.
  • Tribble DR. Resistant pathogens as causes of traveller’s diarrhea globally and impact(s) on treatment failure and recommendations. J Travel Med. 2017;24(suppl_1):S6–S12. doi:10.1093/jtm/taw090.
  • Humphries RM, Schuetz AN. Antimicrobial susceptibility testing of bacteria that cause gastroenteritis. Clin Lab Med. 2015;35(2):313–331. doi:10.1016/j.cll.2015.02.005.
  • Niyogi SK. Increasing antimicrobial resistance-an emerging problem in the treatment of shigellosis. Clin Microbiol Infect. 2007;13(12):1141–1143. doi:10.1111/j.1469-0691.2007.01829.x.
  • Puzari M, Sharma M, Chetia P. Emergence of antibiotic resistant Shigella species: A matter of concern. J Infect Public Health. 2018;11(4):451–454. doi:10.1016/j.jiph.2017.09.025.
  • Baker S, The HC. Recent insights into Shigella: a major contributor to the global diarrhoeal disease burden. Curr Opin Infect Dis. 2018;31(5):449–454. doi:10.1097/QCO.0000000000000475.
  • Shiferaw B, Solghan S, Palmer A, Joyce K, Barzilay EJ, Krueger A, Cieslak P. Antimicrobial susceptibility patterns of shigella isolates in foodborne diseases active surveillance network (FoodNet) sites, 2000-2010. Clin Infect Dis. 2012;54(suppl_5):S458–S463. doi:10.1093/cid/cis230.
  • Kakoullis L, Papachristodoulou E, Chra P, Panos G. Shiga toxin-induced haemolytic uraemic syndrome and the role of antibiotics: a global overview. J Infect. 2019;79(2):75–94. doi:10.1016/j.jinf.2019.05.018.
  • Grif K, Dierich MP, Karch H, Allerberger F. Strain-specific differences in the amount of Shiga toxin released from enterohemorrhagic escherichia coli O157 following exposure to subinhibitory concentrations of antimicrobial agents. Eur J Clin Microbiol Infect Dis. 1998;17(11):761–766. doi:10.1007/s100960050181.
  • Ferreccio C, Prado V, Ojeda A, Cayyazo M, Abrego P, Guers L, Levine MM. Epidemiologic patterns of acute diarrhea and endemic shigella infections in children in a poor periurban setting in Santiago, Chile. Am J Epidemiol. 1991;134(6):614–627. doi:10.1093/oxfordjournals.aje.a116134.
  • Abu-Elyazeed RR, Wierzba TF, Frenck RW, Putnam SD, Rao MR, Savarino SJ, Kamal KA, Peruski LF Jr., Abd-El Messih IA, El-Alkamy SA, et al. Epidemiology of Shigella-associated diarrhea in rural Egyptian children. Am J Trop Med Hyg. 2004;71(3):367–372. doi:10.4269/ajtmh.2004.71.367.
  • Formal SB, Oaks EV, Olsen RE, Wingfield-Eggleston M, Snoy PJ, Cogan JP. Effect of prior infection with virulent Shigella flexneri 2a on the resistance of monkeys to subsequent infection with Shigella sonnei. J Infect Dis. 1991;164(3):533–537. doi:10.1093/infdis/164.3.533.
  • Kotloff KL, Nataro JP, Losonsky GA, Wasserman SS, Hale TL, Taylor DN, Sadoff JC, Levine MM. A modified Shigella volunteer challenge model in which the inoculum is administered with bicarbonate buffer: clinical experience and implications for Shigella infectivity. Vaccine. 1995;13(16):1488–1494. doi:10.1016/0264-410X(95)00102-7.
  • Cohen D, Green MS, Block C, Rouach T, Ofek I. Serum antibodies to lipopolysaccharide and natural immunity to shigellosis in an Israeli military population. J Infect Dis. 1988;157(5):1068–1071. doi:10.1093/infdis/157.5.1068.
  • Cohen D, Green MS, Block C, Slepon R, Ofek I. Prospective study of the association between serum antibodies to lipopolysaccharide O antigen and the attack rate of shigellosis. J Clin Microbiol. 1991;29(2):386–389. doi:10.1128/JCM.29.2.386-389.1991.
  • Livio S, Strockbine NA, Panchalingam S, Tennant SM, Barry EM, Marohn ME, Antonio M, Hossain A, Mandomando I, Ochieng JB, et al. Shigella isolates from the global enteric multicenter study inform vaccine development. Clin Infect Dis. 2014;59(7):933–941. doi:10.1093/cid/ciu468.
  • Levine MM, Kotloff KL, Barry EM, Pasetti MF, Sztein MB. Clinical trials of Shigella vaccines: two steps forward and one step back on a long, hard road. Nat Rev Microbiol. 2007;5(7):540–553. doi:10.1038/nrmicro1662.
  • Mani S, Wierzba T, Walker RI. Status of vaccine research and development for Shigella. Vaccine. 2016;34(26):2887–2894. doi:10.1016/j.vaccine.2016.02.075.
  • Turbyfill KR, Hartman AB, Oaks EV. Isolation and characterization of a Shigella flexneri invasin complex subunit vaccine. Infect Immun. 2000;68(12):6624–6632. doi:10.1128/IAI.68.12.6624-6632.2000.
  • Li A, Rong ZC, Ekwall E, Forsum U, Lindberg AA. Serum antibody-responses against shigella lipopolysaccharides and invasion plasmid-coded antigens in shigella infected swedish patients. Scand J Infect Dis. 1993;25(5):569–577. doi:10.3109/00365549309008545.
  • Li A, Zhao CR, Ekwall E, Lindberg AA. Serum IgG antibody responses to shigella invasion plasmid-coded antigens detected by immunoblot. Scand J Infect Dis. 1994;26(4):435–445. doi:10.3109/00365549409008617.
  • Oberhelman RA, Kopecko DJ, Salazarlindo E, Gotuzzo E, Buysse JM, Venkatesan MM, Yi A, Fernandezprada C, Guzman M, Leonbarua R, et al. Prospective study of systemic and mucosal immune responses in dysenteric patients to specific Shigella invasion plasmid antigens and lipopolysaccharides.. Infect Immun. 1991;59(7] has been updated. OK?):2341–2350. doi:10.1128/IAI.59.7.2341-2350.1991.
  • Vandeverg LL, Herrington DA, Boslego J, Lindberg AA, Levine MM. Age-Specific prevalence of serum antibodies to the invasion plasmid and lipopolysaccharide antigens of shigella species in chilean and North American Populations. J Infect Dis. 1992;166(1] has been updated. OK?):158–161. doi:10.1093/infdis/166.1.158.
  • Martinez-Becerra FJ, Chen XT, Dickenson NE, Choudhari SP, Harrison K, Clements JD, Picking WD, Van De Verg LL, Walker RI, Picking WL. Characterization of a novel fusion protein from IpaB and IpaD of Shigella spp.and its potential as a pan-Shigella vaccine. Infect Immun. 2013;81(12):4470–4477. doi:10.1128/IAI.00859-13.
  • Roy C, Clements JD, Picking WD, Freytag LC. Protective vaccine against shigellosis composed of a Shigella IpaB-IpaD fusion protein (DBF) in combination with the adjuvant dmLT. Presented at: Vaccines for Enteric Diseases; 2017 Oct 9-11; Albufeira, Portugal.
  • Hartman AB, Venkatesan MM. Construction of a Stable attenuated shigella sonnei δvirg vaccine strain, wrss1, and protective efficacy and immunogenicity in the guinea pig keratoconjunctivitis model. Infect Immun. 1998;66(9):4572–4576. doi:10.1128/IAI.66.9.4572-4576.1998.
  • Kotloff KL, Taylor DN, Sztein MB, Wasserman SS, Losonsky GA, Nataro JP, Venkatesan M, Hartman A, Picking WD, Katz DE, et al. Phase I evaluation of δvirg shigella sonnei live, attenuated, oral vaccine strain wrss1 in healthy adults. Infect Immun. 2002;70(4):2016–2021. doi:10.1128/IAI.70.4.2016-2021.2002.
  • Orr N, Katz DE, Atsmon J, Radu P, Yavzori M, Halperin T, Sela T, Kayouf R, Klein Z, Ambar R, et al. Community-based safety, immunogenicity, and transmissibility study of the Shigella sonnei WRSS1 vaccine in Israeli volunteers. Infect Immun. 2005;73(12):8027–8032. doi:10.1128/IAI.73.12.8027-8032.2005.
  • Raqib R, Sarker P, Zaman K, Alam NH, Wierzba TF, Maier N, Talukder K, Baqui AH, Suvarnapunya AE, Qadri F, et al. A phase I trial of WRSS1, a Shigella sonnei live oral vaccine in Bangladeshi adults and children. Hum Vaccin Immunother. 2019;15(6):1326–1337. doi:10.1080/21645515.2019.1575165.
  • Pitisuttithum P, Islam D, Chamnanchanunt S, Ruamsap N, Khantapura P, Kaewkungwal J, Kittitrakul C, Luvira V, Dhitavat J, Venkatesan MM, et al. Clinical trial of an oral live shigella sonnei vaccine candidate, wrss1, in thai adults. Clin Vaccine Immunol. 2016;23(7):564–575. doi:10.1128/CVI.00665-15.
  • Barnoy S, Jeong KI, Helm RF, Suvarnapunya AE, Ranallo RT, Tzipori S, Venkatesan MM. Characterization of WRSs2 and WRSs3, new second-generation virG(icsA)-based Shigella sonnei vaccine candidates with the potential for reduced reactogenicity. Vaccine. 2010;28(6):1642–1654. doi:10.1016/j.vaccine.2009.11.001.
  • Barnoy S, Baqar S, Kaminski RW, Collins T, Nemelka K, Hale TL, Ranallo RT, Venkatesan MM. Shigella sonnei vaccine candidates WRSs2 and WRSs3 are as immunogenic as WRSS1, a clinically tested vaccine candidate, in a primate model of infection. Vaccine. 2011;29(37):6371–6378. doi:10.1016/j.vaccine.2011.04.115.
  • Frenck RW, Baqar S, Alexander W, Dickey M, McNeal M, El-Khorazaty J, Baughman H, Hoeper A, Barnoy S, Suvarnapunya AE, et al. A Phase I trial to evaluate the safety and immunogenicity of WRSs2 and WRSs3; two live oral candidate vaccines against Shigella sonnei. Vaccine. 2018;36(32):4880–4889. doi:10.1016/j.vaccine.2018.06.063.
  • Kotloff KL, Simon JK, Pasetti MF, Sztein MB, Wooden SL, Livio S, Nataro JP, Blackwelder WC, Barry EM, Picking W, et al. Safety and immunogenicity of CVD 1208s, a live, oral δguaba δsen δset shigella flexneri 2a vaccine grown on animal-free media. Hum Vaccin. 2007;3(6):268–275. doi:10.4161/hv.4746.
  • Kotloff KL, Pasetti MF, Barry EM, Nataro JP, Wasserman SS, Sztein MB, Picking WD, Levine MM. Deletion in the shigella enterotoxin genes further attenuates shigella flexneri 2a bearing guanine auxotrophy in a phase 1 trial of CVD 1204 and CVD 1208. J Infect Dis. 2004;190(10):1745–1754. doi:10.1086/424680.
  • Dharmasena MN, Osorio M, Takeda K, Stibitz S, Kopecko DJ. Stable chromosomal expression of shigella flexneri 2a and 3a o-antigens in the live salmonella oral vaccine vector Ty21a. Clin Vaccine Immunol. 2017;24(12):e00181–17. doi:10.1128/CVI.00181-17.
  • Wu Y, Chakravarty S, Li ML, Wai TT, Hoffman SL, Sim BKL. Development of a live attenuated bivalent oral vaccine against Shigella sonnei shigellosis and typhoid fever. J Infect Dis. 2017;215(2):259–268. doi:10.1093/infdis/jiw528.
  • Wu Y, Wai TT, Jackson JM, Li M, Chakravarty S, James ER, Huang H, Laney V, Zhang W, Sack DA, et al. Development and characterization of Salmonella enterica serovar Typhi Ty21a vaccine platform: the promise and insight for vaccines against Shigellosis, ETEC diarrhea, typhoid fever, and non-typhoid salmonellosis. Presented at: Vaccines for Enteric Diseases; 2017 Oct 9-11; Albufeira, Portugal.
  • Girardi P, Harutyunyan S, Neuhauser I, Szijártó V, Nagy G, Nagy E, Henics T Pre-clinical findings with ShigETEC, a combined Shigella and ETEC vaccine that represents paradigm shifts in Shigella vaccine approaches. Presented at: Vaccines for Enteric Diseases; 2017 Oct 9-11; Albufeira, Portugal.
  • McKenzie R, Walker RI, Nabors GS, Van de Verg LL, Carpenter C, Gomes G, Forbes E, Tian JH, Yang HH, Pace JL, et al. Safety and immunogenicity of an oral, inactivated, whole-cell vaccine for Shigella sonnei: preclinical studies and a Phase I trial. Vaccine. 2006;24(18):3735–3745. doi:10.1016/j.vaccine.2005.07.014.
  • Kaminski RW, Wu M, Turbyfill KR, Clarkson K, Tai B, Bourgeois AL, Van De Verg LL, Walker RI, Oaks EV. Development and Preclinical Evaluation of a Trivalent, Formalin-Inactivated Shigella Whole-Cell Vaccine. Clin Vaccine Immunol. 2014;21(3):366–382. doi:10.1128/CVI.00683-13.
  • Kim MJ, Moon YH, Kim H, Rho S, Shin YK, Song M, Walker R, Czerkinsky C, Kim DW, Kim JO. Cross-protective shigella whole-cell vaccine with a truncated o-polysaccharide chain. Front Microbiol. 2018;9:2609. doi:10.3389/fmicb.2018.02609.
  • Barman S, Koley H, Ramamurthy T, Chakrabarti MK, Shinoda S, Nair GB, Takeda Y. Protective immunity by oral immunization with heat-killed Shigella strains in a guinea pig colitis model. Microbiol Immunol. 2013;57(11):762–771. doi:10.1111/1348-0421.12095.
  • Barman S, Koley H, Nag D, Shinoda S, Nair GB, Takeda Y. Passive immunity with multi-serotype heat-killed Shigellae in neonatal mice. Microbiol Immunol. 2014;58(8):463–466. doi:10.1111/1348-0421.12164.
  • Nag D, Sinha R, Mitra S, Barman S, Takeda Y, Shinoda S, Chakrabarti MK, Koley H. Heat killed multi-serotype Shigella immunogens induced humoral immunity and protection against heterologous challenge in rabbit model. Immunobiology. 2015;220(11):1275–1283. doi:10.1016/j.imbio.2015.07.002.
  • Taylor DN, Trofa AC, Sadoff J, Chu CY, Bryla D, Shiloach J, Cohen D, Ashkenazi S, Lerman Y, Egan W, et al. Synthesis, Characterization, and Clinical-Evaluation of Conjugate Vaccines Composed of the O-Specific Polysaccharides of Shigella dysenteriae type 1, Shigella flexneri type 2a, and Shigella sonnei (Plesiomonas-Shigelloides) Bound to Bacterial Toxoids. Infect Immun. 1993;61(9):3678–3687. doi:10.1128/IAI.61.9.3678-3687.1993.
  • Cohen D, Ashkenazi S, Green M, Lerman Y, Slepon R, Robin G, Orr N, Taylor DN, Sadoff JC, Chu CY, et al. Safety and immunogenicity of investigational Shigella conjugate vaccines in Israeli volunteers.. Infect Immun. 1996;64(10):4074–4077. doi:10.1128/IAI.64.10.4074-4077.1996.
  • Cohen D, Ashkenazi S, Green MS, Gdalevich M, Robin G, Slepon R, Yavzori M, Orr N, Block C, Ashkenazi I, et al. Double-blind vaccine-controlled randomised efficacy trial of an investigational Shigella sonnei conjugate vaccine in young adults. Lancet. 1997;349(9046):155–159. doi:10.1016/S0140-6736(96)06255-1.
  • Passwell JH, Ashkenzi S, Banet-Levi Y, Ramon-Saraf R, Farzam N, Lerner-Geva L, Even-Nir H, Yerushalmi B, Chu CY, Shiloach J, et al. Age-related efficacy of Shigella O-specific polysaccharide conjugates in 1–4-year-old Israeli children. Vaccine. 2010;28(10):2231–2235. doi:10.1016/j.vaccine.2009.12.050.
  • Pavliakova D, Chu CY, Bystricky S, Tolson NW, Shiloach J, Kaufman JB, Bryla DA, Robbins JB, Schneerson R. Treatment with succinic anhydride improves the immunogenicity ofshigella flexneri type 2a o-specific polysaccharide–protein conjugates in mice. Infect Immun. 1999;67(10):5526–5529. doi:10.1128/IAI.67.10.5526-5529.1999.
  • Pavliakova D, Moncrief JS, Lyerly DM, Schiffman G, Bryla DA, Robbins JB, Schneerson R. Clostridium difficile recombinant toxin A repeating units as a carrier protein for conjugate vaccines: studies of pneumococcal type 14, Escherichia coli K1, and Shigella flexneri type 2a polysaccharides in mice. Infect Immun. 2000;68:2161–2166.
  • Feldman MF, Wacker M, Hernandez M, Hitchen PG, Marolda CL, Kowarik M, Morris HR, Dell A, Valvano MA, Aebi M. Engineering N-linked protein glycosylation with diverse O antigen lipopolysaccharide structures in Escherichia coli. Proc Natl Acad Sci USA. 2005;102(8):3016–3021. doi:10.1073/pnas.0500044102.
  • Vozza NF, Feldman MF. Glyco-engineering O-antigen-based vaccines and diagnostics in E. coli. Methods Mol Biol. 2015;1321:57–70.
  • Barel LA, Mulard LA. Classical and novel strategies to develop Shigella glycoconjugate vaccine: from concept to efficacy in human. Hum Vaccin Immunother. 2019;15(6):1338–1356. doi:10.1080/21645515.2019.1606972.
  • Hatz CFR, Bally B, Rohrer S, Steffen R, Kramme S, Siegrist CA, Wacker M, Alaimo C, Fonck VG. Safety and immunogenicity of a candidate bioconjugate vaccine against Shigella dysenteriae type 1 administered to healthy adults: A single blind, partially randomized Phase I study. Vaccine. 2015;33(36):4594–4601. doi:10.1016/j.vaccine.2015.06.102.
  • Riddle MS, Kaminski RW, Di Paolo C, Porter CK, Gutierrez RL, Clarkson KA, Weerts HE, Duplessis C, Castellano A, Alaimo C, et al. Safety and immunogenicity of a candidate bioconjugate vaccine against shigella flexneri 2a administered to healthy adults: a single-blind, randomized phase i study. Clin Vaccine Immunol. 2016;23(12] has been updated. OK?):908–917. doi:10.1128/CVI.00224-16.
  • Pozsgay V, Chu CY, Pannell L, Wolfe J, Robbins JB, Schneerson R. Protein conjugates of synthetic saccharides elicit higher levels of serum IgG lipopolysaccharide antibodies in mice than do those of the O-specific polysaccharide from Shigella dysenteriae type 1. Proc Natl Acad Sci U S A. 1999;96(9] has been updated. OK?):5194–5197. doi:10.1073/pnas.96.9.5194.
  • Phalipon A, Tanguy M, Grandjean C, Guerreiro C, Belot F, Cohen D, Sansonetti PJ, Mulard LA. A synthetic carbohydrate-protein conjugate vaccine candidate against shigella flexneri 2a Infection. J Immunol. 2009;182(4):2241–2247. doi:10.4049/jimmunol.0803141.
  • Gerke C, Colucci AM, Giannelli C, Sanzone S, Vitali CG, Sollai L, Rossi O, Martin LB, Auerbach J, Di Cioccio V, et al. Production of a shigella sonnei vaccine based on Generalized Modules for Membrane Antigens (GMMA), 1790GAHB. PLoS One. 2015;10(8):e0134478. doi:10.1371/journal.pone.0134478.
  • Obiero CW, Ndiaye AGW, Scire AS, Kaunyangi BM, Marchetti E, Gone AM, Schutte LD, Riccucci D, Auerbach J, Saul A, et al. A Phase 2a randomized study to evaluate the safety and immunogenicity of the 1790gahb generalized modules for membrane antigen vaccine against shigella sonnei administered intramuscularly to adults from a shigellosis-Endemic Country. Front Immunol. 2017;8:1884.
  • Oaks EV, Picking WD, Picking WL. Antibody response of monkeys to invasion plasmid antigen D after infection with Shigella spp.. Clin Diagn Lab Immun. 1996;3(2):242–245. doi:10.1128/CDLI.3.2.242-245.1996.
  • Turbyfill KR, Kaminski RW, Oaks EV. Immunogenicity and efficacy of highly purified invasin complex vaccine from Shigella flexneri 2a. Vaccine. 2008;26(10):1353–1364. doi:10.1016/j.vaccine.2007.12.040.
  • Hueck CJ. Type III protein secretion systems in bacterial pathogens of animals and plants. Microbiol Mol Biol Rev. 1998;62:379–433.
  • Oaks EV, Turbyfill KR. Development and evaluation of a Shigella flexneri 2a and S. sonnei bivalent invasin complex (Invaplex) vaccine. Vaccine. 2006;24(13):2290–2301. doi:10.1016/j.vaccine.2005.11.040.
  • Tribble D, Kaminski R, Cantrell J, Nelson M, Porter C, Baqar S, Williams C, Arora R, Saunders J, Ananthakrishnan M, et al. Safety and immunogenicity of a Shigella flexneri 2a Invaplex 50 intranasal vaccine in adult volunteers. Vaccine. 2010;28(37):6076–6085. doi:10.1016/j.vaccine.2010.06.086.
  • Riddle MS, Kaminski RW, Williams C, Porter C, Baqar S, Kordis A, Gilliland T, Lapa J, Coughlin M, Soltis C, et al. Safety and immunogenicity of an intranasal Shigella flexneri 2a Invaplex 50 vaccine. Vaccine. 2011;29(40):7009–7019. doi:10.1016/j.vaccine.2011.07.033.
  • Turbyfill KR, Clarkson KA, Vortherms AR, Oaks EV, Kaminski RW. Assembly, Biochemical Characterization, Immunogenicity, Adjuvanticity, and Efficacy of Shigella Artificial Invaplex. Msphere. 2018;3(2):e00583–17. doi:10.1128/mSphere.00583-17.
  • World Health Organization. Future directions for research on enterotoxigenic Escherichia coli vaccines for developing countries.. Wkly Epidemiol Rec. 2006;81(11):97–107.
  • Sanders JW, Putnam SD, Riddle MS, Tribble DR. Military importance of diarrhea: lessons from the Middle East. Curr Opin Gastroenterol. 2005;21:9–14.
  • Jiang ZD, DuPont HL. Etiology of travellers’ diarrhea. J Travel Med. 2017;24(suppl_1):S13–S16. doi:10.1093/jtm/tax003.
  • Nataro JP, Kaper JB. Diarrheagenic Escherichia coli. Clin Microbiol Rev. 1998;11:142–201.
  • Svennerholm AM, Tobias J. Vaccines against enterotoxigenic Escherichia coli. Expert Rev Vaccines. 2008;7(6):795–804. doi:10.1586/14760584.7.6.795.
  • Zhang W, Sack DA. Progress and hurdles in the development of vaccines against enterotoxigenic Escherichia coli in humans. Expert Rev Vaccines. 2012;11(6):677–684. doi:10.1586/erv.12.37.
  • Walker RI. An assessment of enterotoxigenic Escherichia coli and Shigella vaccine candidates for infants and children. Vaccine. 2015;33(8):954–965. doi:10.1016/j.vaccine.2014.11.049.
  • Zhang W, Sack DA. Current progress in developing subunit vaccines against enterotoxigenic escherichia coli -associated diarrhea. Clin Vaccine Immunol. 2015;22(9):983–991. doi:10.1128/CVI.00224-15.
  • Walker R, Dull P. Combination vaccine strategies to prevent enteric infections. Vaccine. 2017;35(49):6790–6792. doi:10.1016/j.vaccine.2017.06.076.
  • Qadri F, Svennerholm AM, Faruque AS, Sack RB. Enterotoxigenic Escherichia coli in developing countries: epidemiology, microbiology, clinical features, treatment, and prevention. Clin Microbiol Rev. 2005;18(3):465–483. doi:10.1128/CMR.18.3.465-483.2005.
  • Svennerholm AM, Lundgren A. Recent progress toward an enterotoxigenic Escherichia coli vaccine. Expert Rev Vaccines. 2012;11(4] has been updated. OK?):495–507. doi:10.1586/erv.12.12.
  • Isidean SD, Riddle MS, Savarino SJ, Porter CK. A systematic review of ETEC epidemiology focusing on colonization factor and toxin expression. Vaccine. 2011;29(37):6167–6178. doi:10.1016/j.vaccine.2011.06.084.
  • Jertborn M, Ahren C, Holmgren J, Svennerholm AM. Safety and immunogenicity of an oral inactivated enterotoxigenic Escherichia coli vaccine. Vaccine. 1998;16(2–3):255–260. doi:10.1016/S0264-410X(97)00169-2.
  • Lebens M, Shahabi V, Backstrom M, Houze T, Lindblad M, Holmgren J. Synthesis of hybrid molecules between heat-labile enterotoxin and cholera toxin B subunits: potential for use in a broad-spectrum vaccine. Infect Immun. 1996;64(6] has been updated. OK?):2144–2150. doi:10.1128/IAI.64.6.2144-2150.1996.
  • Ahren C, Jertborn M, Svennerholm AM. Intestinal immune responses to an inactivated oral enterotoxigenic Escherichia coli vaccine and associated immunoglobulin A responses in blood. Infect Immun. 1998;66(7 et al., 2016] has been updated. OK?):3311–3316. doi:10.1128/IAI.66.7.3311-3316.1998.
  • Cohen D, Orr N, Haim M, Ashkenazi S, Robin G, Green MS, Ephros M, Sela T, Slepon R, Ashkenazi I, et al. Safety and immunogenicity of two different lots of the oral, killed enterotoxigenic Escherichia coli-Cholera toxin B subunit vaccine in Israeli young adults. Infect Immun. 2000;68(8):4492–4497. doi:10.1128/IAI.68.8.4492-4497.2000.
  • Qadri F, Wenneras C, Ahmed F, Asaduzzaman M, Saha D, Albert MJ, Sack RB, Svennerholm A. Safety and immunogenicity of an oral, inactivated enterotoxigenic Escherichia coli plus cholera toxin B subunit vaccine in Bangladeshi adults and children. Vaccine. 2000;18(24):2704–2712. doi:10.1016/S0264-410X(00)00056-6.
  • Savarino SJ, Hall ER, Bassily S, Brown FM, Youssef F, Wierzba TF, Peruski L, El-Masry NA, Safwat M, Rao M, et al. Oral, Inactivated, whole cell enterotoxigenic escherichia coli plus cholera toxin b subunit vaccine: results of the initial evaluation in children. J Infect Dis. 1999;179(1):107–114. doi:10.1086/314543.
  • Qadri F, Ahmed T, Ahmed F, Bradley Sack R, Sack DA, Svennerholm AM. Safety and immunogenicity of an oral, inactivated enterotoxigenic Escherichia coli plus cholera toxin B subunit vaccine in Bangladeshi children 18-36 months of age. Vaccine. 2003;21(19–20] has been updated. OK?):2394–2403. doi:10.1016/S0264-410X(03)00077-X.
  • Savarino SJ, Hall ER, Bassily S, Wierzba TF, Youssef FG, Peruski LF Jr., Abu-Elyazeed R, Rao M, Francis WM, El Mohamady H, et al. Introductory evaluation of an oral, killed whole cell enterotoxigenic Escherichia coli plus cholera toxin B subunit vaccine in Egyptian infants. Pediatr Infect Dis J. 2002;21(4):322–330. doi:10.1097/00006454-200204000-00012.
  • Sack DA, Shimko J, Torres O, Bourgeois AL, Francia DS, Gustafsson B, Karnell A, Nyquist I, Svennerholm AM. Randomised, double-blind, safety and efficacy of a killed oral vaccine for enterotoxigenic E. coli diarrhoea of travellers to Guatemala and Mexico. Vaccine. 2007;25(22):4392–4400. doi:10.1016/j.vaccine.2007.03.034.
  • Holmgren J, Bourgeois L, Carlin N, Clements J, Gustafsson B, Lundgren A, Nygren E, Tobias J, Walker R, Svennerholm AM. Development and preclinical evaluation of safety and immunogenicity of an oral ETEC vaccine containing inactivated E. coli bacteria overexpressing colonization factors CFA/I, CS3, CS5 and CS6 combined with a hybrid LT/CT B subunit antigen, administered alone and together with dmLT adjuvant.. Vaccine. 2013;31(20):2457–2464. doi:10.1016/j.vaccine.2013.03.027.
  • Lundgren A, Bourgeois L, Carlin N, Clements J, Gustafsson B, Hartford M, Holmgren J, Petzold M, Walker R, Svennerholm AM. Safety and immunogenicity of an improved oral inactivated multivalent enterotoxigenic Escherichia coli (ETEC) vaccine administered alone and together with dmLT adjuvant in a double-blind, randomized, placebo-controlled Phase I study. Vaccine. 2014;32(52):7077–7084. doi:10.1016/j.vaccine.2014.10.069.
  • Akhtar M, Chowdhury MI, Bhuiyan TR, Kaim J, Ahmed T, Rafique TA, Khan A, Rahman SIA, Khanam F, Begum YA, et al. Evaluation of the safety and immunogenicity of the oral inactivated multivalent enterotoxigenic Escherichia coli vaccine ETVAX in Bangladeshi adults in a double-blind, randomized, placebo-controlled Phase I trial using electrochemiluminescence and ELISA assays for immunogenicity analyses.. Vaccine. 2019;37(37):5645–5656. doi:10.1016/j.vaccine.2018.11.040.
  • Leach S, Lundgren A, Carlin N, Lofstrand M, Svennerholm AM. Cross-reactivity and avidity of antibody responses induced in humans by the oral inactivated multivalent enterotoxigenic Escherichia coli (ETEC) vaccine ETVAX. Vaccine. 2017;35(32):3966–3973. doi:10.1016/j.vaccine.2017.06.006.
  • Qadri F, Akhtar M, Bhuiyan TR, Chowdhury MI, Ahmed T, Rafique TA, Khan A, Rahman SIA, Khanam F, Lundgren A, et al. Safety and immunogenicity of the oral, inactivated, enterotoxigenic Escherichia coli vaccine ETVAX in Bangladeshi children and infants: a double-blind, randomised, placebo-controlled phase 1/2 trial. Lancet Infect Dis. 2020;20(2):208–219. doi:10.1016/S1473-3099(19)30571-7.
  • Seo H, Zhang W. Development of effective vaccines for enterotoxigenic Escherichia coli. Lancet Infect Dis. 2020;20(2):150–152. doi:10.1016/S1473-3099(19)30631-0.
  • Turner AK, Stephens JC, Beavis JC, Greenwood J, Gewert C, Randall R, Freeman D, Darsley MJ. Generation and Characterization of a Live Attenuated Enterotoxigenic Escherichia coli Combination Vaccine Expressing Six Colonization Factors and Heat-Labile Toxin Subunit B. Clin Vaccine Immunol. 2011;18(12):2128–2135. doi:10.1128/CVI.05345-11.
  • Harro C, Sack D, Bourgeois AL, Walker R, Denearing B, Feller A, Chakraborty S, Buchwaldt C, Darsley MJ. A combination vaccine consisting of three live attenuated enterotoxigenic Escherichia coli strains expressing a range of colonization factors and heat-labile toxin subunit B is well tolerated and immunogenic in a placebo-controlled double-blind phase I trial in healthy adults.. Clin Vaccine Immunol. 2011;18(12] has been updated. OK?):2118–2127. doi:10.1128/CVI.05342-11.
  • Harro C, David S, Darsley M, Bourgeois AL, DeNearing B, Feller A, Chakraborty S, Marcum A, Comendador R, Buchwaldt C, et al. Volunteers receiving live attenuated ETEC vaccine (ACE527) have reduced severity of illness following H10407 challenge. Presented at: Vaccines for Enteric Diseases; 2011 Sep 14–16; Cannes, France.
  • Darsley MJ, Chakraborty S, DeNearing B, Sack DA, Feller A, Buchwaldt C, Bourgeois AL, Walker R, Harro CD. The oral, live attenuated enterotoxigenic Escherichia coli vaccine ACE527 reduces the incidence and severity of diarrhea in a human challenge model of diarrheal disease. Clin Vaccine Immunol. 2012;19(12):1921–1931. doi:10.1128/CVI.00364-12.
  • Harro C, Louis Bourgeois A, Sack D, Walker R, DeNearing B, Brubaker J, Maier N, Fix A, Dally L, Chakraborty S, et al. Live attenuated enterotoxigenic Escherichia coli (ETEC) vaccine with dmLT adjuvant protects human volunteers against virulent experimental ETEC challenge. Vaccine. 2019;37(14):1978–1986. doi:10.1016/j.vaccine.2019.02.025.
  • Sincock SA, Hall ER, Woods CM, O’Dowd A, Poole ST, McVeigh AL, Nunez G, Espinoza N, Miller M, Savarino SJ. Immunogenicity of a prototype enterotoxigenic Escherichia coli adhesin vaccine in mice and nonhuman primates. Vaccine. 2016;34(2):284–291. doi:10.1016/j.vaccine.2015.11.017.
  • Rollenhagen JE, Woods CM, O’Dowd A, Poole ST, Tian JH, Guebre-Xabier M, Ellingsworth L, Prouty MG, Glenn G, Savarino SJ. Evaluation of transcutaneous immunization as a delivery route for an enterotoxigenic E. coli adhesin-based vaccine with CfaE, the colonization factor antigen 1 (CFA/I) tip adhesin. Vaccine. 2019;37(42):6134–6138. doi:10.1016/j.vaccine.2019.08.057.
  • Savarino SJ, McKenzie R, Tribble DR, Porter CK, O’Dowd A, Cantrell JA, Sincock SA, Poole ST, DeNearing B, Woods CM, et al. prophylactic efficacy of hyperimmune bovine colostral antiadhesin antibodies against enterotoxigenic escherichia coli diarrhea: a randomized, double-blind, placebo-controlled, phase 1 trial. J Infect Dis. 2017;216(1):7–13. doi:10.1093/infdis/jix144.
  • Anantha RP, McVeigh AL, Lee LH, Agnew MK, Cassels FJ, Scott DA, Whittam TS, Savarino SJ. Evolutionary and functional relationships of colonization factor antigen i and other class 5 adhesive fimbriae of enterotoxigenic Escherichia coli. Infect Immun. 2004;72(12):7190–7201. doi:10.1128/IAI.72.12.7190-7201.2004.
  • Seo H, Ruan X, Duan Q, Garcia C, Sack DA, Zhang W MecVax, a broadly protective subunit vaccine against enterotoxigenic Escherichia coli (ETEC) diarrhea. Presented at: Vaccines for Enteric Diseases; 2019 Oct 16-18; Lausanne, Switzerland.
  • Ruan X, Robertson DC, Nataro JP, Clements JD, Zhang W. Characterization of Heat-Stable (STa) Toxoids of Enterotoxigenic Escherichia coli Fused to Double Mutant Heat-Labile Toxin Peptide in Inducing Neutralizing Anti-STa Antibodies. Infect Immun. 2014;82(5):1823–1832. doi:10.1128/IAI.01394-13.
  • Nandre R, Ruan X, Duan Q, Zhang W. Enterotoxigenic Escherichia coli heat-stable toxin and heat-labile toxin toxoid fusion 3xSTa N12S -dmLT induces neutralizing anti-STa antibodies in subcutaneously immunized mice. FEMS Microbiol Lett. 2016;363(21] has been updated. OK?):1–6. doi:10.1093/femsle/fnw246.
  • Duan Q, Huang J, Xiao N, Seo H, Zhang W. Neutralizing anti-STa antibodies derived from enterotoxigenic Escherichia coli (ETEC) toxoid fusions with heat-stable toxin (STa) mutant STaN12S, STaL9A/N12S or STaN12S/A14T show little cross-reactivity with guanylin or uroguanylin. Appl Environ Microbiol. 2018;84:e01737–17.
  • Nandre RM, Duan Q, Wang Y, Zhang W. Passive antibodies derived from intramuscularly immunized toxoid fusion 3xSTa N12S -dmLT protect against STa+ enterotoxigenic Escherichia coli (ETEC) diarrhea in a pig model. Vaccine. 2017;35(4):552–556. doi:10.1016/j.vaccine.2016.12.021.
  • Seo H, Lu T, Nandre RM, Duan Q, Zhang W. Immunogenicity characterization of genetically fused or chemically conjugated heat-stable toxin toxoids of enterotoxigenic Escherichia coli in mice and pigs. FEMS Microbiol Lett. 2019;366(4):fnz037. doi:10.1093/femsle/fnz037.
  • Ruan X, Knudsen DE, Wollenberg KM, Sack DA, Zhang W. Multiepitope fusion antigen induces broadly protective antibodies that prevent adherence of escherichia coli strains expressing colonization factor antigen I (CFA/I), CFA/II, and CFA/IV. Clin Vaccine Immunol. 2014;21(2):243–249. doi:10.1128/CVI.00652-13.
  • Seo H, Lu T, Mani S, Bourgeois AL, Walker R, Sack DA, Zhang W. Adjuvant effect of enterotoxigenic Escherichia coli (ETEC) double-mutant heat-labile toxin (dmLT) on systemic immunogenicity induced by the CFA/I/II/IV MEFA ETEC vaccine: dose-related enhancement of antibody responses to seven ETEC adhesins (CFA/I, CS1-CS6). Hum Vaccin Immunother. 2019;23:1–7.
  • Seo H, Nandre RM, Nietfeld J, Chen Z, Duan Q, Zhang W. Antibodies induced by enterotoxigenic Escherichia coli (ETEC) adhesin major structural subunit and minor tip adhesin subunit equivalently inhibit bacteria adherence in vitro. PLoS One. 2019;14(5):e0216076. doi:10.1371/journal.pone.0216076.
  • Duan Q, Lu T, Garcia C, Yanez C, Nandre RM, Sack DA, Zhang W. Co-administered Tag-Less Toxoid Fusion 3xSTaN12S-mnLTR192G/L211A and CFA/I/II/IV MEFA (Multiepitope Fusion Antigen) Induce Neutralizing Antibodies to 7 Adhesins (CFA/I, CS1-CS6) and Both Enterotoxins (LT, STa) of Enterotoxigenic Escherichia coli (ETEC). Front Microbiol. 2018;9:1198. doi:10.3389/fmicb.2018.01198.
  • Fleckenstein JM, Rasko DA. Overcoming Enterotoxigenic Escherichia coli Pathogen Diversity: translational Molecular Approaches to Inform Vaccine Design. Methods Mol Biol. 2016;1403:363–383.
  • Kuhlmann FM, Martin J, Hazen TH, Vickers TJ, Pashos M, Okhuysen PC, Gomez-Duarte OG, Cebelinski E, Boxrud D, Del Canto F, et al. Conservation and global distribution of non-canonical antigens in Enterotoxigenic Escherichia coli. PLoS Negl Trop Dis. 2019;13(11):e0007825. doi:10.1371/journal.pntd.0007825.
  • Govasli ML, Diaz Y, Puntervoll P. Virus-like particle-display of the enterotoxigenic Escherichia coli heat-stable toxoid STh-A14T elicits neutralizing antibodies in mice. Vaccine. 2019;37(43):6405–6414. doi:10.1016/j.vaccine.2019.09.004.
  • Diaz Y, Govasli ML, Zegeye ED, Sommerfelt H, Steinsland H, Puntervoll P. Immunizations with enterotoxigenic escherichia coli heat-stable toxin conjugates engender toxin-neutralizing antibodies in mice that also cross-react with guanylin and uroguanylin. Infect Immun. 2019;87(7):e00099–19. doi:10.1128/IAI.00099-19.
  • Donnenberg MS, Finlay BB. Combating enteropathogenic Escherichia coli (EPEC) infections: the way forward. Trends Microbiol. 2013;21(7):317–319. doi:10.1016/j.tim.2013.05.003.
  • Sanchez-Villamil JI, Tapia D, Torres AG. Development of a Gold Nanoparticle Vaccine against Enterohemorrhagic Escherichia coli O157:H7. mBio. 2019;10(4):e01869–19. doi:10.1128/mBio.01869-19.
  • Ali M, Nelson AR, Lopez AL, Sack DA. Updated global burden of cholera in endemic countries. PLoS Negl Trop Dis. 2015;9(6):e0003832. doi:10.1371/journal.pntd.0003832.
  • Clemens JD, Harris JR, Khan MR, Kay BA, Yunus MD, Svennerholm AM, Sack DA, Chakraborty J, Stanton BF, Khan MU, et al. Field trial of oral cholera vaccines in Bangladesh. Lancet. 1986;2(8499):124–127. doi:10.1016/S0140-6736(86)91944-6.
  • Clemens JD, Sack DA, Harris JR, Vanloon F, Chakraborty J, Ahmed F, Rao MR, Khan MR, Yunus M, Huda N, et al. Field Trial of Oral Cholera Vaccines in Bangladesh - Results from 3-Year Follow-Up. Lancet. 1990;335(8684):270–273.
  • Clemens JD, Sack DA, Harris JR, Van Loon F, Chakraborty J, Ahmed F, Rao MR, Khan MR, Yunus M, Huda N, et al. Field trial of oral cholera vaccines in Bangladesh: results from three-year follow-up. Lancet. 1990;335(8684):270–273. doi:10.1016/0140-6736(90)90080-O.
  • Trach DD, Cam PD, Ke NT, Rao MR, Dinh D, Hang PV, Hung NV, Canh DG, Thiem VD, Naficy A, et al. Investigations into the safety and immunogenicity of a killed oral cholera vaccine developed in Viet Nam. Bull World Health Organ. 2002;80(1):2–8.
  • Anh DD, Canh DG, Lopez AL, Thiem VD, Long PT, Son NH, Deen J, von Seidlein L, Carbis R, Han SH, et al. Safety and immunogenicity of a reformulated Vietnamese bivalent killed, whole-cell, oral cholera vaccine in adults. Vaccine. 2007;25(6):1149–1155. doi:10.1016/j.vaccine.2006.09.049.
  • Shamsuzzaman S, Ahmed T, Mannoor K, Begum YA, Bardhan PK, Sack RB, Sack DA, Svennerholm AM, Holmgren J, Qadri F. Robust gut associated vaccine-specific antibody-secreting cell responses are detected at the mucosal surface of Bangladeshi subjects after immunization with an oral killed bivalent V. cholerae O1/O139 whole cell cholera vaccine: comparison with other mucosal and systemic responses.. Vaccine. 2009;27(9):1386–1392. doi:10.1016/j.vaccine.2008.12.041.
  • Saha A, Chowdhury MI, Khanam F, Bhuiyan MS, Chowdhury F, Khan AI, Khan IA, Clemens J, Ali M, Cravioto A, et al. Safety and immunogenicity study of a killed bivalent (O1 and O139) whole-cell oral cholera vaccine Shanchol, in Bangladeshi adults and children as young as 1 year of age. Vaccine. 2011;29(46):8285–8292. doi:10.1016/j.vaccine.2011.08.108.
  • Sur D, Kanungo S, Sah B, Manna B, Ali M, Paisley AM, Niyogi SK, Park JK, Sarkar B, Puri MK, et al. Efficacy of a low-cost, inactivated whole-cell oral cholera vaccine: results from 3 years of follow-up of a randomized, controlled trial. PLoS Negl Trop Dis. 2011;5(10):e1289. doi:10.1371/journal.pntd.0001289.
  • Sur D, Lopez AL, Kanungo S, Paisley A, Manna B, Ali M, Niyogi SK, Park JK, Sarkar B, Puri MK, et al. Efficacy and safety of a modified killed-whole-cell oral cholera vaccine in India: an interim analysis of a cluster-randomised, double-blind, placebo-controlled trial. Lancet. 2009;374(9702):1694–1702. doi:10.1016/S0140-6736(09)61297-6.
  • Bhattacharya SK, Sur D, Ali M, Kanungo S, You YA, Manna B, Sah B, Niyogi SK, Park JK, Sarkar B, et al. 5 year efficacy of a bivalent killed whole-cell oral cholera vaccine in Kolkata, India: a cluster-randomised, double-blind, placebo-controlled trial. Lancet Infect Dis. 2013;13(12):1050–1056. doi:10.1016/S1473-3099(13)70273-1.
  • Qadri F, Ali M, Chowdhury F, Khan AI, Saha A, Khan IA, Begum YA, Bhuiyan TQR, Chowdhury MI, Uddin MJ, et al. Feasibility and effectiveness of oral cholera vaccine in an urban endemic setting in Bangladesh: a cluster randomised open-label trial. Lancet. 2015;386(10001):1362–1371. doi:10.1016/S0140-6736(15)61140-0.
  • Qadri F, Wierzba TF, Ali M, Chowdhury F, Khan AI, Saha A, Khan IA, Asaduzzaman M, Akter A, Khan A, et al. Efficacy of a Single-Dose, Inactivated Oral Cholera Vaccine in Bangladesh. N Engl J Med. 2016;374(18):1723–1732. doi:10.1056/NEJMoa1510330.
  • Baik YO, Choi SK, Kim JW, Yang JS, Kim IY, Kim CW, Hong JH. Safety and Immunogenicity Assessment of an Oral Cholera Vaccine through Phase I Clinical Trial in Korea. J Korean Med Sci. 2014;29(4):494–501. doi:10.3346/jkms.2014.29.4.494.
  • Russo P, Ligsay AD, Olveda R, Choi SK, Kim DR, Park JY, Park JY, Syed KA, Dey A, Kim YH, et al. A randomized, observer-blinded, equivalence trial comparing two variations of Euvichol®, a bivalent killed whole-cell oral cholera vaccine, in healthy adults and children in the Philippines. Vaccine. 2018;36(29):4317–4324. doi:10.1016/j.vaccine.2018.05.102.
  • Baik YO, Choi SK, Olveda RM, Espos RA, Ligsay AD, Montellano MB, Yeam JS, Yang JS, Park JY, Kim DR, et al. A randomized, non-inferiority trial comparing two bivalent killed, whole cell, oral cholera vaccines (Euvichol vs Shanchol) in the Philippines. Vaccine. 2015;33(46):6360–6365. doi:10.1016/j.vaccine.2015.08.075.
  • Levine MM, Herrington D, Losonsky G, Tall B, Kaper JB, Ketley J, Tacket CO, Cryz S. Safety, immunogenicity, and efficacy of recombinant live oral cholera vaccines, CVD-103 and CVD-103-Hgr. Lancet. 1988;2:468–470.
  • Tacket CO, Losonsky G, Nataro JP, Cryz SJ, Edelman R, Kaper JB, Levine MM. Onset and duration of protective immunity in challenged volunteers after vaccination with live oral cholera vaccine CVD l03-HgR. J Infect Dis. 1992;166(4):837–841. doi:10.1093/infdis/166.4.837.
  • Tacket CO, Cohen MB, Wasserman SS, Losonsky G, Livio S, Kotloff K, Edelman R, Kaper JB, Cryz SJ, Giannella RA, et al. Randomized, double-blind, placebo-controlled, multicentered trial of the efficacy of a single dose of live oral cholera vaccine CVD 103-HgR in preventing cholera following challenge with Vibrio cholerae O1 El Tor Inaba three months after vaccination. Infect Immun. 1999;67(12):6341–6345. doi:10.1128/IAI.67.12.6341-6345.1999.
  • Richie E, Punjabi NH, Sidharta Y, Peetosutan K, Sukandar M, Wasserman SS, Lesmana M, Wangsasaputra F, Pandam S, Levine MM, et al. Efficacy trial of single-dose live oral cholera vaccine CVD 103-HgR in North Jakarta, Indonesia, a cholera-endemic area. Vaccine. 2000;18(22):2399–2410. doi:10.1016/S0264-410X(00)00006-2.
  • Kenner JR, Coster TS, Taylor DN, Trofa AF, Barreraoro M, Hyman T, Adams JM, Beattie DT, Killeen KP, Spriggs DR, et al. Peru-15, an Improved Live Attenuated Oral Vaccine Candidate for Vibrio Cholerae O1. J Infect Dis. 1995;172(4):1126–1129. doi:10.1093/infdis/172.4.1126.
  • Chowdhury MI, Sheikh A, Qadri F. Development of Peru-15 (CholeraGarde®), a live-attenuated oral cholera vaccine: 1991–2009. Expert Rev Vaccines. 2009;8(12):1643–1652. doi:10.1586/erv.09.137.
  • Cohen MB, Giannella RA, Bean J, Taylor DN, Parker S, Hoeper A, Wowk S, Hawkins J, Kochi SK, Schiff G, et al. Randomized, controlled human challenge study of the safety, immunogenicity, and protective efficacy of a single dose of Peru-15, a live attenuated oral cholera vaccine. Infect Immun. 2002;70(4):1965–1970. doi:10.1128/IAI.70.4.1965-1970.2002.
  • Qadri F, Chowdhury MI, Faruque SM, Salam MA, Ahmed T, Begum YA, Saha A, Al Tarique A, Seidlein LV, Park E, et al. Peru-15, a live attenuated oral cholera vaccine, is safe and immunogenic in Bangladeshi toddlers and infants. Vaccine. 2007;25(2):231–238. doi:10.1016/j.vaccine.2006.08.031.
  • Qadri F, Chowdhury MI, Faruque SM, Salam MA, Ahmed T, Begum YA, Saha A, Alam MS, Zaman K, Seidlein LV, et al. Randomized, controlled study of the safety and immunogenicity of Peru-15, a live attenuated oral vaccine candidate for cholera, in adult volunteers in Bangladesh. J Infect Dis. 2005;192(4):573–579. doi:10.1086/432074.
  • Crim SM, Iwamoto M, Huang JY, Griffin PM, Gilliss D, Cronquist AB, Cartter M, Tobin-D’Angelo M, Blythe D, Smith K, et al. Incidence and trends of infection with pathogens transmitted commonly through food-Foodborne Diseases Active Surveillance Network, 10 U.S. sites, 2006-2013. MMWR Morb Mortal Wkly Rep. 2014;63(15):328–332.
  • Tack DM, Marder EP, Griffin PM, Cieslak PR, Dunn J, Hurd S, Scallan E, Lathrop S, Muse A, Ryan P, et al. Preliminary incidence and trends of infections with pathogens transmitted commonly through food-foodborne diseases active surveillance network, 10 U.S. sites, 2015-2018. MMWR Morb Mortal Wkly Rep. 2019;68(16):369–373. doi:10.15585/mmwr.mm6816a2.
  • Coker AO, Isokpehi RD, Thomas BN, Amisu KO, Obi CL. Human campylobacteriosis in developing countries. Emerg Infect Dis. 2002;8(3):237–244. doi:10.3201/eid0803.010233.
  • Klena JD, Parker CT, Knibb K, Ibbitt JC, Devane PM, Horn ST, Miller WG, Konkel ME. Differentiation of Campylobacter coli, Campylobacter jejuni, Campylobacter lari, and Campylobacter upsaliensis by a multiplex PCR developed from the nucleotide sequence of the lipid A gene lpxA. J Clin Microbiol. 2004;42(12] has been updated. OK?):5549–5557. doi:10.1128/JCM.42.12.5549-5557.2004.
  • Dasti JI, Tareen AM, Lugert R, Zautner AE, Gross U. Campylobacter jejuni: a brief overview on pathogenicity-associated factors and disease-mediating mechanisms. Int J Med Microbiol. 2010;300(4):205–211. doi:10.1016/j.ijmm.2009.07.002.
  • Konkel ME, Garvis SG, Tipton SL, Anderson, Jr DE Jr., Cieplak, Jr W Jr. Identification and molecular cloning of a gene encoding a fibronectin-binding protein (CadF) from Campylobacter jejuni. Mol Microbiol. 1997;24(5):953–963. doi:10.1046/j.1365-2958.1997.4031771.x.
  • Pei Z, Blaser MJ. PEB1, the major cell-binding factor of Campylobacter jejuni, is a homolog of the binding component in gram-negative nutrient transport systems.. J Biol Chem. 1993;268:18717–18725.
  • Jin S, Joe A, Lynett J, Hani EK, Sherman P, Chan VL. JlpA, a novel surface-exposed lipoprotein specific to Campylobacter jejuni, mediates adherence to host epithelial cells. Mol Microbiol. 2001;39(5):1225–1236. doi:10.1111/j.1365-2958.2001.02294.x.
  • Cortes-Bratti X, Karlsson C, Lagergard T, Thelestam M, Frisan T. The Haemophilus ducreyi Cytolethal Distending Toxin Induces Cell Cycle Arrest and Apoptosis via the DNA Damage Checkpoint Pathways. J Biol Chem. 2001;276(7):5296–5302. doi:10.1074/jbc.M008527200.
  • Korlath JA, Osterholm MT, Judy LA, Forfang JC, Robinson RA. A point-source outbreak of campylobacteriosis associated with consumption of raw milk. J Infect Dis. 1985;152(3):592–596. doi:10.1093/infdis/152.3.592.
  • Baqar S, Applebee LA, Bourgeois AL. Immunogenicity and protective efficacy of a prototype Campylobacter killed whole-cell vaccine in mice.. Infect Immun. 1995;63(9):3731–3735. doi:10.1128/IAI.63.9.3731-3735.1995.
  • Baqar S, Bourgeois AL, Schultheiss PJ, Walker RI, Rollins DM, Haberberger RL, Pavlovskis OR. Safety and immunogenicity of a prototype oral whole-cell killed Campylobacter vaccine administered with a mucosal adjuvant in non-human primates. Vaccine. 1995;13(1):22–28. doi:10.1016/0264-410X(95)80006-Y.
  • Tribble DR, Baqar S, Thompson SA. Development of a Human Vaccine.. In: Nachamkin I, Szymanski CM, Blaser MJ editors. Campylobacter. 3rd. Washington (DC): American Society of Microbiology; 2008. p. 429–444.
  • Lee LH, Burg E 3rd, Baqar S, Bourgeois AL, Burr DH, Ewing CP, Trust TJ, Guerry P, Orndorff PE. Evaluation of a truncated recombinant flagellin subunit vaccine against Campylobacter jejuni. Infect Immun. 1999;67(11):5799–5805. doi:10.1128/IAI.67.11.5799-5805.1999.
  • Monteiro MA, Baqar S, Hall ER, Chen YH, Porter CK, Bentzel DE, Applebee L, Guerry P. Capsule polysaccharide conjugate vaccine against diarrheal disease caused by Campylobacter jejuni. Infect Immun. 2009;77(3):1128–1136. doi:10.1128/IAI.01056-08.
  • Poly F, Noll AJ, Riddle MS, Porter CK. Update on Campylobacter vaccine development. Hum Vaccin Immunother. 2019;15(6):1389–1400. doi:10.1080/21645515.2018.1528410.
  • Brunette GW. CDC Yellow Book 2020: health Information for International Travel. NY: Oxford University Press; 2020.
  • Scallan E, Hoekstra RM, Angulo FJ, Tauxe RV, Widdowson MA, Roy SL, Jones JL, Griffin PM. Foodborne illness acquired in the United States-major pathogens. Emerg Infect Dis. 2011;17(1):7–15. doi:10.3201/eid1701.P11101.
  • Gordon MA, Banda HT, Gondwe M, Gordon SB, Boeree MJ, Walsh AL, Corkill JE, Hart CA, Gilks CF, Molyneux ME. Non-typhoidal Salmonella bacteraemia among HIV-infected Malawian adults: high mortality and frequent recrudescence. AIDS. 2002;16(12):1633–1641. doi:10.1097/00002030-200208160-00009.
  • MacLennan CA, Levine MM. Invasive nontyphoidal Salmonella disease in Africa: current status. Expert Rev Anti Infect Ther. 2013;11(5):443–446. doi:10.1586/eri.13.27.
  • Kingsley RA, Msefula CL, Thomson NR, Kariuki S, Holt KE, Gordon MA, Harris D, Clarke L, Whitehead S, Sangal V, et al. Epidemic multiple drug resistant Salmonella Typhimurium causing invasive disease in sub-Saharan Africa have a distinct genotype. Genome Res. 2009;19(12):2279–2287. doi:10.1101/gr.091017.109.
  • de Jong HK, Parry CM, van der Poll T, Wiersinga WJ. Host-pathogen interaction in invasive Salmonellosis. PLoS Pathog. 2012;8(10):e1002933. doi:10.1371/journal.ppat.1002933.
  • Hindle Z, Chatfield SN, Phillimore J, Bentley M, Johnson J, Cosgrove CA, Ghaem-Maghami M, Sexton A, Khan M, Brennan FR, et al. Characterization of Salmonella enterica derivatives harboring defined aroC and Salmonella pathogenicity island 2 type III secretion system (ssaV) mutations by immunization of healthy volunteers. Infect Immun. 2002;70(7):3457–3467. doi:10.1128/IAI.70.7.3457-3467.2002.
  • Chatfield SN, Fairweather N, Charles I, Pickard D, Levine M, Hone D, Posada M, Strugnell RA, Dougan G. Construction of a genetically defined Salmonella typhi Ty2 aroA, aroC mutant for the engineering of a candidate oral typhoid-tetanus vaccine. Vaccine. 1992;10(1):53–60. doi:10.1016/0264-410X(92)90420-O.
  • Tennant SM, Wang JY, Galen JE, Simon R, Pasetti MF, Gat O, Levine MM, Fang FC. Engineering and preclinical evaluation of attenuated nontyphoidal Salmonella strains serving as live oral vaccines and as reagent strains. Infect Immun. 2011;79(10):4175–4185. doi:10.1128/IAI.05278-11.
  • Simon R, Tennant SM, Wang JY, Schmidlein PJ, Lees A, Ernst RK, Pasetti MF, Galen JE, Levine MM. Salmonella enterica Serovar Enteritidis Core O Polysaccharide Conjugated to H:g,m Flagellin as a Candidate Vaccine for Protection against Invasive Infection with S.Enteritidis. Infect Immun. 2011;79(10):4240–4249. doi:10.1128/IAI.05484-11.
  • Martinez-Becerra FJ, Kumar P, Vishwakarma V, Kim JH, Arizmendi O, Middaugh CR, Picking WD, Picking WL, Payne SM. Characterization and Protective Efficacy of Type III Secretion Proteins as a Broadly Protective Subunit Vaccine against Salmonella enterica Serotypes. Infect Immun. 2018;86(3):e00473–17. doi:10.1128/IAI.00473-17.
  • Wu HJ, Wang AH, Jennings MP. Discovery of virulence factors of pathogenic bacteria. Curr Opin Chem Biol. 2008;12(1):93–101. doi:10.1016/j.cbpa.2008.01.023.
  • Chao CC, Chelius D, Zhang T, Mutumanje E, Ching WM. Insight into the virulence of Rickettsia prowazekii by proteomic analysis and comparison with an avirulent strain. Biochim Biophys Acta. 2007;1774(3):373–381. doi:10.1016/j.bbapap.2007.01.001.
  • Duan Q, Lee KH, Nandre RM, Garcia C, Chen J, Zhang W. MEFA (multiepitope fusion antigen)-Novel Technology for Structural Vaccinology, Proof from Computational and Empirical Immunogenicity Characterization of an Enterotoxigenic Escherichia coli (ETEC) Adhesin MEFA. J Vaccines Vaccin. 2017;8:367.
  • Ruan X, Sack DA, Zhang W. Genetic fusions of a CFA/I/II/IV MEFA (multiepitope fusion antigen) and a toxoid fusion of heat-stable toxin (STa) and heat-labile toxin (LT) of enterotoxigenic Escherichia coli (ETEC) retain broad anti-CFA and antitoxin antigenicity. PLoS One. 2015;10(3] has been updated. OK?):e0121623. doi:10.1371/journal.pone.0121623.
  • Nandre RM, Ruan X, Duan Q, Sack DA, Zhang W. Antibodies derived from an enterotoxigenic Escherichia coli (ETEC) adhesin tip MEFA (multiepitope fusion antigen) against adherence of nine ETEC adhesins: CFA/I, CS1, CS2, CS3, CS4, CS5, CS6, CS21 and EtpA. Vaccine. 2016;34(31):3620–3625. doi:10.1016/j.vaccine.2016.04.003.
  • Rausch D, Ruan X, Nandre R, Duan Q, Hashish E, Casey TA, Zhang W. Antibodies derived from a toxoid MEFA (multiepitope fusion antigen) show neutralizing activities against heat-labile toxin (LT), heat-stable toxins (STa, STb), and Shiga toxin 2e (Stx2e) of porcine enterotoxigenic Escherichia coli (ETEC). Vet Microbiol. 2017;202:79–89. doi:10.1016/j.vetmic.2016.02.002.
  • Nandre R, Ruan X, Lu T, Duan Q, Sack D, Zhang W. Enterotoxigenic Escherichia coli Adhesin-Toxoid Multiepitope Fusion Antigen CFA/I/II/IV-3xSTaN12S-mnLTG192G/L211A-Derived Antibodies Inhibit Adherence of Seven Adhesins, Neutralize Enterotoxicity of LT and STa Toxins, and Protect Piglets against Diarrhea. Infect Immun. 2018;86:e00550–17.
  • Seo H, Anvari S, Li S, Lu T, Sack DA, Zhang W Immunogenicity characterization and pre-clinical evaluation of a combo vaccine for Shigella and enterotoxigenic Escherichia coli. Presented at: Vaccines for Enteric Diseases; 2019 Oct 16-18; Lausanne, Switzerland.
  • Qadri F, Bhuiyan TR, Sack DA, Svennerholm AM. Immune responses and protection in children in developing countries induced by oral vaccines. Vaccine. 2013;31(3):452–460. doi:10.1016/j.vaccine.2012.11.012.

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