Safety and immunogenicity of three dose levels of an investigational, highly purified Vero cell rabies vaccine: A randomized, controlled, observer-blinded, Phase II study with a simulated post-exposure regimen in healthy adults

References

• Hampson K, Coudeville L, Lembo T, Sambo M, Kieffer A, Attlan M, Barrat J, Blanton JD, Briggs DJ, Cleaveland S, et al. Correction: estimating the global burden of endemic canine rabies. PLoS Negl Trop Dis. 2015;9(5):e0003786. doi:10.1371/journal.pntd.0003786.
   PubMed Web of Science ®Google Scholar
• World Health Organization. Rabies epidemiology and burden of disease; 2022 [accessed 2023 Sept 1]. https://www.who.int/teams/control-of-neglected-tropical-diseases/rabies/epidemiology-and-burden.
   Google Scholar
• Hampson K, Coudeville L, Lembo T, Sambo M, Kieffer A, Attlan M, Barrat J, Blanton JD, Briggs DJ, Cleaveland S, et al. Estimating the global burden of endemic canine rabies. PLoS Negl Trop Dis. 2015;9(4):e0003709. doi:10.1371/journal.pntd.0003709.
   PubMed Web of Science ®Google Scholar
• World Health Organization. Rabies fact sheet; 2021 [accessed 2023 Sept 1]. https://www.who.int/news-room/fact-sheets/detail/rabies.
   Google Scholar
• Hampson K, Dobson A, Kaare M, Dushoff J, Magoto M, Sindoya E, Cleaveland S, Kieny MP. Rabies exposures, post-exposure prophylaxis and deaths in a region of endemic canine rabies. PLoS Negl Trop Dis. 2008;2(11):e339. doi:10.1371/journal.pntd.0000339.
   PubMed Web of Science ®Google Scholar
• Anderson A, Shwiff SA. The Cost of canine rabies on four continents. Transbound Emerg Dis. 2015;62(4):446–11. doi:10.1111/tbed.12168.
   PubMed Web of Science ®Google Scholar
• Patil SU, Shreffler WG. Novel vaccines: technology and development. J Allergy Clin Immunol. 2019;143(3):844–51. doi:10.1016/j.jaci.2018.05.021.
   PubMed Web of Science ®Google Scholar
• Montagnon B, Fanget B. Chapter 26: purified Vero cell vaccine for humans. In: Meslin F-X-K Koprowski H, World Health Organization, editors. Laboratory techniques in rabies. 4th ed. Geneva (Switzerland): WHO; 1996. p. 285.
   Google Scholar
• World Health Organization. WHO consultation on public health and animal transmissible spongiform encephalopathies: epidemiology, risk and Research requirements, Geneva, Switzerland, 1-3 December 1999. Geneva: World Health Organization; 2000.
   Google Scholar
• Li R, Huang L, Li J, Mo Z, He B, Wang Y, Wu X, Minutello M, Guinet-Morlot F, Pichon S. A next-generation, serum-free, highly purified Vero cell rabies vaccine is safe and as immunogenic as the reference vaccine verorab(R) when administered according to a post-exposure regimen in healthy children and adults in China. Vaccine. 2013;31:5940–7. doi:10.1016/j.vaccine.2013.10.043.
   PubMed Web of Science ®Google Scholar
• Pichon S, Guinet-Morlot F, Minutello M, Donazzolo Y, Rouzier R, Chassard D, Fitoussi S, Hou V. A serum-free, purified Vero cell rabies vaccine is safe and as immunogenic as the reference vaccine verorab™ for pre-exposure use in healthy adults: results from a randomized controlled phase-II trial. Vaccine. 2013;31(18):2295–301. doi:10.1016/j.vaccine.2013.02.058.
   PubMed Web of Science ®Google Scholar
• Pichon S, Moureau A, Petit C, Chu L, Essink B, Muse D, Saleh J, Guinet-Morlot F, Minutello AM. Safety and immunogenicity of a serum-free purified Vero rabies vaccine in healthy adults: a randomised phase II pre-exposure prophylaxis study. Vaccine. 2022;40(33):4780–7. doi:10.1016/j.vaccine.2022.06.040.
   PubMed Web of Science ®Google Scholar
• Quiambao B, Montalban C, Minutello AM, Guinet-Morlot F, Moureau A, Petit C, Pichon S. Serum-free purified Vero rabies vaccine is safe and immunogenic in children: results of a randomized phaseII pre-exposure prophylaxis regimen study. Vaccine. 2022;40(35):5170–8. doi:10.1016/j.vaccine.2022.06.061.
   PubMed Web of Science ®Google Scholar
• Morgeaux S, Poirier B, Ragan CI, Wilkinson D, Arabin U, Guinet-Morlot F, Levis R, Meyer H, Riou P, Shaid S, et al. Replacement of in vivo human rabies vaccine potency testing by in vitro glycoprotein quantification using ELISA - Results of an international collaborative study. Vaccine. 2017;35:966–71. doi:10.1016/j.vaccine.2016.12.039.
   PubMed Web of Science ®Google Scholar
• Chabaud-Riou M, Moreno N, Guinchard F, Nicolai MC, Niogret-Siohan E, Sève N, Manin C, Guinet-Morlot F, Riou P. G-protein based ELISA as a potency test for rabies vaccines. Biologicals. 2017;46:124–9. doi:10.1016/j.biologicals.2017.02.002.
   PubMed Web of Science ®Google Scholar
• Mulder R, Singh AB, Hamilton A, Das P, Outhred T, Morris G, Bassett D, Baune BT, Berk M, Boyce P, et al. The limitations of using randomised controlled trials as a basis for developing treatment guidelines. Evid Based Ment Health. 2018;21(1):4–6. doi:10.1136/eb-2017-102701.
   PubMed Web of Science ®Google Scholar
• World Health Organization. Rabies vaccines: WHO position paper, April 2018. Wkly Epidemiol Rec. 2018;16:201–20. doi:10.1016/j.vaccine.2018.06.061.
   Google Scholar
• Manning SE, Rupprecht CE, Fishbein D, Hanlon CA, Lumlertdacha B, Guerra M, Meltzer MI, Dhankhar P, Vaidya SA, Jenkins SR, et al. Human rabies prevention–United States, 2008: recommendations of the advisory committee on immunization practices. MMWR Recomm Rep. 2008;57:1–28.
   PubMedGoogle Scholar
• World Health Organization. WHO expert consultation on rabies: third report. Geneva: World Health Organization; 2018.
   Google Scholar
• Beaujouan É, Toulemon L. European countries with delayed childbearing are not those with lower fertility. Genus. 2021;77:2. doi:10.1186/s41118-020-00108-0.
   Google Scholar
• Smith JS, Yager PA, Baer GM. A rapid reproducible test for determining rabies neutralizing antibody. Bull World Health Organ. 1973;48:535–41.
   PubMed Web of Science ®Google Scholar
• Timiryasova TM, Luo P, Zheng L, Singer A, Zedar R, Garg S, Petit C, Moore S, Hu BT, Brown M. Rapid fluorescent focus inhibition test optimization and validation: improved detection of neutralizing antibodies to rabies virus. J Immunol Methods. 2019;474:112626. doi:10.1016/j.jim.2019.06.017.
   PubMed Web of Science ®Google Scholar
• Reed LJ, Muench H. A simple method of estimating fifty per cent endpoints12. Am J Epidemiol. 1938;27(3):493–7. doi:10.1093/oxfordjournals.aje.a118408.
   Google Scholar
• Mehari MA, Maeruf H, Robles CC, Woldemariam S, Adhena T, Mulugeta M, Haftu A, Hagose H, Kumsa H. Advanced maternal age pregnancy and its adverse obstetrical and perinatal outcomes in ayder comprehensive specialized hospital, Northern Ethiopia, 2017: a comparative cross-sectional study. BMC Pregnancy Childbirth. 2020;20(1):60. doi:10.1186/s12884-020-2740-6.
   PubMed Web of Science ®Google Scholar
• Moore SM. Challenges of rabies serology: defining context of interpretation. Viruses. 2021;13(8):1516. doi:10.3390/v13081516.
   PubMed Web of Science ®Google Scholar
• Sudarshan MK, Mahendra BJ, Madhusudana SN, Narayana DHA, Sanjay TV, Gangaboraiah, Anandagiri MS. Assessing the relationship between antigenicity and immunogenicity of human rabies vaccines: results of a metaanalysis. Hum Vaccin. 2005;1:187–90. doi:10.4161/hv.1.5.2110.
   PubMed Web of Science ®Google Scholar
• Miranda E, Lacuesta TL, Lacuesta V, Suquila J, Manalo M, Dimaano E . Safety and immunogenicity of purified Vero cell rabies vaccine versus purified chick embryo cell rabies vaccine using pre-exposure and post exposure regimen among healthy volunteers in San Lazaro hospital. Philip J Inte Med. 2014;52:1–7.
   Google Scholar
• Uwanyiligira M, Landry P, Genton B, de Valliere S. Rabies postexposure prophylaxis in routine practice in view of the new centers for disease control and prevention and World Health Organization recommendations. Clin Infect Dis. 2012;55(2):201–5. doi:10.1093/cid/cis384.
   PubMed Web of Science ®Google Scholar
• Gogtay NJ, Munshi R, Ashwath Narayana DH, Mahendra BJ, Kshirsagar V, Gunale B, Moore S, Cheslock P, Thaker S, Deshpande S, et al. Comparison of a novel human rabies monoclonal antibody to human rabies immunoglobulin for postexposure prophylaxis: a Phase 2/3, randomized, single-blind, noninferiority, controlled study. Clin Infect Dis. 2018;66(3):387–95. doi:10.1093/cid/cix791.
   PubMed Web of Science ®Google Scholar
• Sampath G, Banzhoff A, Deshpande A, Malerczyk C, Arora AK, Vakil H, Preiss S. Comparison of the immunogenicity and safety of the purified chick embryo cell rabies vaccine manufactured in India and Germany: a randomized, single blind, multicentre, phase IV clinical study. Hum Vaccin Immunother. 2017;13:1531–8. doi:10.1080/21645515.2017.1307483.
   PubMed Web of Science ®Google Scholar
• Preiss S, Chanthavanich P, Chen LH, Marano C, Buchy P, van Hoorn R, Vonk Noordegraaf M, Mukherjee P. Post-exposure prophylaxis (PEP) for rabies with purified chick embryo cell vaccine: a systematic literature review and meta-analysis. Expert Rev Vaccines. 2018;17(6):525–45. doi:10.1080/14760584.2018.1473765.
   PubMed Web of Science ®Google Scholar
• Wang SY, Sun JF, Liu P, Luo L, Li JX, Zhu FC, Shen XX, Meng FY. Immunogenicity and safety of human diploid cell vaccine (HDCV) vs. purified Vero cell vaccine (PVRV) vs. purified chick embryo cell vaccine (PCECV) used in post-exposure prophylaxis: a systematic review and meta-analysis. Hum Vaccin Immunother. 2022;18(1):2027714. doi:10.1080/21645515.2022.2027714.
   PubMed Web of Science ®Google Scholar
• Matson MA, Schenker E, Stein M, Zamfirova V, Nguyen HB, Bergman GE. Safety and efficacy results of simulated post-exposure prophylaxis with human immune globulin (HRIG; KEDRAB) co-administered with active vaccine in healthy subjects: a comparative phase 2/3 trial. Hum Vaccin Immunother. 2020;16(2):452–9. doi:10.1080/21645515.2019.1656967.
   PubMed Web of Science ®Google Scholar
• Hobart-Porter N, Stein M, Toh N, Amega N, Nguyen HB, Linakis J. Safety and efficacy of rabies immunoglobulin in pediatric patients with suspected exposure. Hum Vaccin Immunother. 2021;17(7):2090–6. doi:10.1080/21645515.2020.1854000.
   PubMed Web of Science ®Google Scholar
• Bernard MC, Boudet F, Pineda-Pena AC, Guinet-Morlot F. Inhibitory effect of concomitantly administered rabies immunoglobulins on the immunogenicity of commercial and candidate human rabies vaccines in hamsters. Sci Rep. 2022;12(1):6570. doi:10.1038/s41598-022-10281-1.
   PubMed Web of Science ®Google Scholar
• Lang J, Simanjuntak GH, Soerjosembodo S, Koesharyono C. Suppressant effect of human or equine rabies immunoglobulins on the immunogenicity of post-exposure rabies vaccination under the 2-1-1 regimen: a field trial in Indonesia. MAS054 clinical investigator group. Bull World Health Organ. 1998;76:491–5.
   PubMed Web of Science ®Google Scholar
• Salva EP, Dimaano EM, Villarama JBR, Suquila JT. An evaluation of the safety and potency of equine rabies immunoglobulin through measurement of suppression on vaccine-induced antibody production among healthy volunteers. Philip J Inte Med. 2014;52:1–7.
   Google Scholar
• Soentjens P, Declercq S. Prophylaxie post-exposition contre la rage, Institute of tropical medicine Antwerp, September 2020. 2020.
   Google Scholar
• UK Health Security Agency. Administration of rabies vaccine and iImmunoglobulin. 2022.
   Google Scholar
• Briggs DJ, Moore SM. The Route of administration of rabies vaccines: comparing the data. Viruses. 2021;13(7):1252. doi:10.3390/v13071252.
   PubMed Web of Science ®Google Scholar
• Rodriguez MC, Fontana D, Garay E, Prieto C. Detection and quantification of anti-rabies glycoprotein antibodies: current state and perspectives. Appl Microbiol Biotechnol. 2021;105(18):6547–57. doi:10.1007/s00253-021-11515-4.
   PubMed Web of Science ®Google Scholar
• Wilde H. Failures of post-exposure rabies prophylaxis. Vaccine. 2007;25(44):7605–9. doi:10.1016/j.vaccine.2007.08.054.
   PubMed Web of Science ®Google Scholar
• Rupprecht CE, Briggs D, Brown CM, Franka R, Katz SL, Kerr HD, Lett SM, Levis R, Meltzer MI, Schaffner W, et al. Use of a reduced (4-dose) vaccine schedule for postexposure prophylaxis to prevent human rabies: recommendations of the advisory committee on immunization practices. MMWR Recomm Rep. 2010;59:1–9.
   PubMedGoogle Scholar
• Rao AK, Briggs D, Moore SM, Whitehill F, Campos-Outcalt D, Morgan RL, Wallace RM, Romero JR, Bahta L, Frey SE, et al. Use of a modified preexposure prophylaxis vaccination schedule to prevent human rabies: recommendations of the advisory committee on immunization practices - United States, 2022. MMWR Morb Mortal Wkly Rep. 2022;71:619–27. doi:10.15585/mmwr.mm7118a2.
   PubMed Web of Science ®Google Scholar
• Audran R, Depraetere G, Genton B, Spertini F, Uwanyiligira M, Mayor C, Thierry A, Zanoni R, Valliere S. Poor immune response to rabies post-exposure prophylaxis: an attempt to understand the underlying mechanisms. JSM Trop Med Res. 2016;1:1009.
   Google Scholar
• Morelli F, Augard C, Bourhy H, Bravo C, Coudeville L, Moore S, Quiambao B, Recuenco S. Immunogenicity of rabies vaccines in postexposure prophylaxis (PEP) or simulated PEP regimens: a systematic literature review and meta-analysis. Presented at: the International Conference on Rabies in the Americas Meeting; 2022 Oct 23–28; Querétaro, Mexico.
   Google Scholar
• Timiryasova TM, Hodge SA, Zheng LY, Singer A, Vincent D, Rahman M, Petit C, Brown M. Preparation and qualification of internal rabies reference standards for use in the rabies rapid fluorescent focus inhibition test. Sci Rep-Uk. 2020;10(1):10. doi:10.1038/s41598-020-66754-8.
   PubMed Web of Science ®Google Scholar
• Mahendra BJ, Narayana DA, Agarkhedkar S, Ravish HS, Harish BR, Agarkhedkar S, Madhusudana SN, Belludi A, Ahmed K, Jonnalagedda R, et al. Comparative study on the immunogenicity and safety of a purified chick embryo cell rabies vaccine (PCECV) administered according to two different simulated post exposure intramuscular regimens (Zagreb versus Essen). Hum Vaccin Immunother. 2015;11:428–34. doi:10.4161/21645515.2014.995059.
   PubMed Web of Science ®Google Scholar