A safe and efficient BCG vectored vaccine to prevent the disease caused by the human Respiratory Syncytial Virus

References

• Nair H, Nokes DJ, Gessner BD, Dherani M, Madhi SA, Singleton RJ, O'Brien KL, Roca A, Wright PF, Bruce N, et al. Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: A systematic review and meta-analysis. Lancet 2010; 375:1545–55; PMID:20399493; https://doi.org/10.1016/S0140-6736(10)60206-1
   PubMed Web of Science ®Google Scholar
• Sweetman LL, Ng YT, Butler IJ, Bodensteiner JB. Neurologic complications associated with respiratory syncytial virus. Pediatr Neurol 2005; 32:307-10; PMID:15866430; https://doi.org/10.1016/j.pediatrneurol.2005.01.010
   PubMed Web of Science ®Google Scholar
• Bont L, Versteegh J, Swelsen WT, Heijnen CJ, Kavelaars A, Brus F, Draaisma JM, Pekelharing-Berghuis M, van Diemen-Steenvoorde RA, Kimpen JL. Natural reinfection with respiratory syncytial virus does not boost virus-specific t-cell immunity. Pediatr Res 2002; 52:363-7; PMID:12193668; https://doi.org/10.1203/00006450-200209000-00009
   PubMed Web of Science ®Google Scholar
• Hall CB. The burgeoning burden of respiratory syncytial virus among children. Infect Disord Drug Targets 2012; 12:92-7; PMID:22335498
   PubMedGoogle Scholar
• PATH. Respiratory syncytial virus. Vaccine development against a major cause of childhood respiratory illness. Http://sites.Path.Org/vaccinedevelopment/respiratory-syncytial-virus-rsv. Accesed 17 febreary 2017. 2016
   Google Scholar
• Hall CB, Walsh EE, Long CE, Schnabel KC. Immunity to and frequency of reinfection with respiratory syncytial virus. J Infect Dis 1991; 163:4; https://doi.org/10.1093/infdis/163.4.693
   Web of Science ®Google Scholar
• Spann KM, Tran KC, Collins PL. Effects of nonstructural proteins ns1 and ns2 of human respiratory syncytial virus on interferon regulatory factor 3, nf-kappab, and proinflammatory cytokines. J Virol 2005; 79:5353-62; PMID:15827150; https://doi.org/10.1128/JVI.79.9.5353-5362.2005
   PubMed Web of Science ®Google Scholar
• Wright PF, Karron RA, Madhi SA, Treanor JJ, King JC, O'Shea A, Ikizler MR, Zhu Y, Collins PL, Cutland C, et al. The interferon antagonist ns2 protein of respiratory syncytial virus is an important virulence determinant for humans. J Infect Dis 2006; 193:573-81; PMID:16425137; https://doi.org/10.1086/499600
   PubMed Web of Science ®Google Scholar
• Segovia J, Sabbah A, Mgbemena V, Tsai SY, Chang TH, Berton MT, Morris IR, Allen IC, Ting JP, Bose S. Tlr2/myd88/nf-κb pathway, reactive oxygen species, potassium efflux activates nlrp3/asc inflammasome during respiratory syncytial virus infection. PLoS One 2012; 7:e29695; PMID:22295065; https://doi.org/10.1371/journal.pone.0029695
   PubMed Web of Science ®Google Scholar
• Triantafilou K, Kar S, Vakakis E, Kotecha S, Triantafilou M. Human respiratory syncytial virus viroporin sh: A viral recognition pathway used by the host to signal inflammasome activation. Thorax 2013; 68:66-75; PMID:23229815; https://doi.org/10.1136/thoraxjnl-2012-202182
   PubMed Web of Science ®Google Scholar
• Munir S, Hillyer P, Le Nouen C, Buchholz UJ, Rabin RL, Collins PL, Bukreyev A. Respiratory syncytial virus interferon antagonist ns1 protein suppresses and skews the human t lymphocyte response. PLoS Pathog 2011; 7:e1001336; PMID:21533073; https://doi.org/10.1371/journal.ppat.1001336
   PubMed Web of Science ®Google Scholar
• Graaff P. Respiratory syncytial virus infection of monocyte-derived dendritic cells decreases their capacity to activate cd4 t cells. J Immunol 2005; 175:5904-11; PMID:16237083; https://doi.org/10.4049/jimmunol.175.9.5904
   PubMed Web of Science ®Google Scholar
• Gonzalez PA, Prado CE, Leiva ED, Carreno LJ, Bueno SM, Riedel CA, Kalergis AM. Respiratory syncytial virus impairs t cell activation by preventing synapse assembly with dendritic cells. Proc Natl Acad Sci U S A 2008; 105:14999-5004; PMID:18818306; https://doi.org/10.1073/pnas.0802555105
   PubMed Web of Science ®Google Scholar
• Gonzalez PA, Bueno SM, Riedel CA, Kalergis AM. Impairment of t cell immunity by the respiratory syncytial virus: Targeting virulence mechanisms for therapy and prophylaxis. Curr Med Chem 2009; 16:4609-25; PMID:19903147; https://doi.org/10.2174/092986709789760724
   PubMed Web of Science ®Google Scholar
• Cespedes PF, Bueno SM, Ramirez BA, Gomez RS, Riquelme SA, Palavecino CE, Mackern-Oberti JP, Mora JE, Depoil D, Sacristan C, et al. Surface expression of the hrsv nucleoprotein impairs immunological synapse formation with t cells. Proc Natl Acad Sci U S A 2014; 111:E3214-23; PMID:25056968; https://doi.org/10.1073/pnas.1400760111
   PubMed Web of Science ®Google Scholar
• Bendelja K, Gagro A, Bace A, Lokar-Kolbas R, Krsulovic-Hresic V, Drazenovic V, Mlinaric-Galinovic G, Rabatic S. Predominant type-2 response in infants with respiratory syncytial virus (rsv) infection demonstrated by cytokine flow cytometry. Clin Exp Immunol 2000; 121:332-8; PMID:10931150; https://doi.org/10.1046/j.1365-2249.2000.01297.x
   PubMed Web of Science ®Google Scholar
• Aoyagi M, Shimojo N, Sekine K, Nishimuta T, Kohno Y. Respiratory syncytial virus infection suppresses ifn-γ production of γδ t cells. Clin Exp Immunol 2003; 131:312-7; PMID:12562394; https://doi.org/10.1046/j.1365-2249.2003.02062.x
   PubMed Web of Science ®Google Scholar
• Zeng S, Wu J, Liu J, Qi F, Liu B. Il-33 receptor (st2) signalling is important for regulation of th2-mediated airway inflammation in a murine model of acute respiratory syncytial virus infection. Scand J Immunol 2015; 81:494-501; PMID:25721734; https://doi.org/10.1111/sji.12284
   PubMed Web of Science ®Google Scholar
• Bertrand P, Lay MK, Piedimonte G, Brockmann PE, Palavecino CE, Hernández J, León MA, Kalergis AM, Bueno SM. Elevated il-3 and il-12p40 levels in the lower airway of infants with rsv-induced bronchiolitis correlate with recurrent wheezing. Cytokine 2015; 76:417-23; PMID:26299549; https://doi.org/10.1016/j.cyto.2015.07.017
   PubMed Web of Science ®Google Scholar
• Mukherjee S, Lindell DM, Berlin AA, Morris SB, Shanley TP, Hershenson MB, Lukacs NW. Il-17-induced pulmonary pathogenesis during respiratory viral infection and exacerbation of allergic disease. Am J Pathol 2011; 179:248-58; PMID:21703407; https://doi.org/10.1016/j.ajpath.2011.03.003
   PubMed Web of Science ®Google Scholar
• Bystrom J, Al-Adhoubi N, Al-Bogami M, Jawad AS, Mageed RA. Th17 lymphocytes in respiratory syncytial virus infection. Viruses 2013; 5:777-91; PMID:23462708; https://doi.org/10.3390/v5030777
   PubMed Web of Science ®Google Scholar
• Fulton RB, Meyerholz DK, Varga SM Foxp3+ cd4 regulatory t cells limit pulmonary immunopathology by modulating the cd8 t cell response during respiratory syncytial virus infection. J Immunol 2010; 185:2382-92; PMID:20639494; https://doi.org/10.4049/jimmunol.1000423
   PubMed Web of Science ®Google Scholar
• Lee DC, Harker JA, Tregoning JS, Atabani SF, Johansson C, Schwarze J, Openshaw PJ. Cd25+ natural regulatory t cells are critical in limiting innate and adaptive immunity and resolving disease following respiratory syncytial virus infection. J Virol 2010; 84:8790-8; PMID:20573822; https://doi.org/10.1128/JVI.00796-10
   PubMed Web of Science ®Google Scholar
• Durant LR, Makris S, Voorburg CM, Loebbermann J, Johansson C, Openshaw PJ Regulatory t cells prevent th2 immune responses and pulmonary eosinophilia during respiratory syncytial virus infection in mice. J Virol 2013; 87:10946-54; PMID:23926350; https://doi.org/10.1128/JVI.01295-13
   PubMed Web of Science ®Google Scholar
• Lu X, McCoy KS, Xu J. Galectin-9 ameliorates respiratory syncytial virus-induced pulmonary immunopathology through regulating the balance between th17 and regulatory t cells. Virus Res 2015; 195:162-71; PMID:25451068; https://doi.org/10.1016/j.virusres.2014.10.011
   PubMed Web of Science ®Google Scholar
• de Almeida Nagata DE, Demoor T, Ptaschinski C, Ting HA, Jang S, Reed M, Mukherjee S, Lukacs NW. Il-27r-mediated regulation of il-17 controls the development of respiratory syncytial virus-associated pathogenesis. Am J Pathol 2014; 184:1807-18; PMID:24726498; https://doi.org/10.1016/j.ajpath.2014.02.004
   PubMed Web of Science ®Google Scholar
• Kim HW, Canchola JG, Brandt CD. Respiratory syncytial virus disease in infants despite prior administration of antigenic inactivated vaccine. Am J Epidemiol 1969; 89:422-34; PMID:4305198; https://doi.org/10.1093/oxfordjournals.aje.a120955
   PubMed Web of Science ®Google Scholar
• Kruijsen D, Schijf MA, Lukens MV, van Uden NO, Kimpen JL, Coenjaerts FE, van Bleek GM. Local innate and adaptive immune responses regulate inflammatory cell influx into the lungs after vaccination with formalin inactivated rsv. Vaccine 2011; 29:2730-41; PMID:21316502; https://doi.org/10.1016/j.vaccine.2011.01.087
   PubMed Web of Science ®Google Scholar
• Carbonell-Estrany X, Simões EA, Dagan R, Hall CB, Harris B, Hultquist M, Connor EM, Losonsky GA; Motavizumab Study Group. Motavizumab for prophylaxis of respiratory syncytial virus in high-risk children: A noninferiority trial. Pediatrics 2010; 125:e35-51; PMID:20008423; https://doi.org/10.1542/peds.2008-1036
   PubMed Web of Science ®Google Scholar
• Fernández P, Trenholme A, Abarca K, Griffin MP, Hultquist M, Harris B, Losonsky GA; Motavizumab Study Group. A phase 2, randomized, double-blind safety and pharmacokinetic assessment of respiratory syncytial virus (rsv) prophylaxis with motavizumab and palivizumab administered in the same season. BMC Pediatr 2010; 10:38; PMID:20525274; https://doi.org/10.1186/1471-2431-10-38
   PubMed Web of Science ®Google Scholar
• Robbie GJ, Criste R, Dall'acqua WF, Jensen K, Patel NK, Losonsky GA, Griffin MP. A novel investigational fc-modified humanized monoclonal antibody, motavizumab-yte, has an extended half-life in healthy adults. Antimicrob Agents Chemother 2013; 57:6147-53; PMID:24080653; https://doi.org/10.1128/AAC.01285-13
   PubMed Web of Science ®Google Scholar
• Griffin MP, Khan AA, Esser MT, Jensen K, Takas T, Kankam MK, Villafana T, Dubovsky F. Safety, tolerability, and pharmacokinetics of the respiratory syncytial virus-prefusion f-targeting monoclonal antibody with an extended half-life, medi8897, in healthy adults. Antimicrob Agents Chemother 2017; 61(3):e01714-16
   Web of Science ®Google Scholar
• Boyce TG, Mellen BG, Mitchel EF, Jr, Wright PF, Griffin MR. Rates of hospitalization for respiratory syncytial virus infection among children in medicaid. J Pediatr 2000; 137:865-70; PMID:11113845; https://doi.org/10.1067/mpd.2000.110531
   PubMed Web of Science ®Google Scholar
• Krarup A, Truan D, Furmanova-Hollenstein P, Bogaert L, Bouchier P, Bisschop IJ, Widjojoatmodjo MN, Zahn R, Schuitemaker H, McLellan JS, et al. A highly stable prefusion rsv f vaccine derived from structural analysis of the fusion mechanism. Nat Commun 2015; 3:8143; https://doi.org/10.1038/ncomms9143
   Web of Science ®Google Scholar
• Smith G, Raghunandan R, Wu Y, Liu Y, Massare M, Nathan M. Respiratory syncytial virus fusion glycoprotein expressed in insect cells form protein nanoparticles that induce protective immunity in cotton rats. PLoS One 2012; 7(11):e50852
   PubMed Web of Science ®Google Scholar
• Cimica V, Boigard H, Bhatia B, Fallon JT, Alimova A, Gottlieb P, Galarza JM. Novel respiratory syncytial virus-like particle vaccine composed of the postfusion and prefusion conformations of the f glycoprotein. Clin Vaccine Immunol 2016; 23:451-9; PMID:27030590; https://doi.org/10.1128/CVI.00720-15
   PubMed Web of Science ®Google Scholar
• Liang B, Munir S, Amaro-Carambot E, Surman S, Mackow N, Yang L, Buchholz UJ, Collins PL, Schaap-Nutt A. Chimeric bovine/human parainfluenza virus type 3 expressing respiratory syncytial virus (rsv) f glycoprotein: Effect of insert position on expression, replication, immunogenicity, stability, and protection against rsv infection. J Virol 2014; 88:4237-50; PMID:24478424; https://doi.org/10.1128/JVI.03481-13
   PubMed Web of Science ®Google Scholar
• Xu J, Ding Y, Yang Y. Enhancement of mucosal and cellular immune response in mice by vaccination with respiratory syncytial virus DNA encapsulated with transfersome. Viral Immunol 2008; 21:483-90; PMID:19115938; https://doi.org/10.1089/vim.2008.0044
   PubMed Web of Science ®Google Scholar
• Hwang HS, Lee YT, Kim KH, Park S, Kwon YM, Lee Y, Ko EJ, Jung YJ, Lee JS, Kim YJ, et al. Combined virus-like particle and fusion protein-encoding DNA vaccination of cotton rats induces protection against respiratory syncytial virus without causing vaccine-enhanced disease. Virology 2016; 494:215-24; PMID:27123586; https://doi.org/10.1016/j.virol.2016.04.014
   PubMed Web of Science ®Google Scholar
• Bueno SM, Gonzalez PA, Cautivo KM, Mora JE, Leiva ED, Tobar HE. Protective t cell immunity against respiratory syncytial virus is efficiently induced by recombinant bcg. Proc Natl Acad Sci USA 2008; 105:20822-7; PMID:19075247; https://doi.org/10.1073/pnas.0806244105
   PubMed Web of Science ®Google Scholar
• Cautivo KM, Bueno SM, Cortes CM, Wozniak A, Riedel CA, Kalergis AM. Efficient lung recruitment of respiratory syncytial virus-specific th1 cells induced by recombinant bacillus calmette-guerin promotes virus clearance and protects from infection. J Immunol 2010; 185:7633-45; PMID:21084664; https://doi.org/10.4049/jimmunol.0903452
   PubMed Web of Science ®Google Scholar
• Abubakar I, Pimpin L, Ariti C, Beynon R, Mangtani P, Sterne JA, Fine PE, Smith PG, Lipman M, Elliman D, et al. Systematic review and meta-analysis of the current evidence on the duration of protection by bacillus calmette-guérin vaccination against tuberculosis. Health Technol Assess 2013; 17:1-372; PMID:24021245; https://doi.org/10.3310/hta17370
   PubMed Web of Science ®Google Scholar
• Marchant A, Goetghebuer T, Ota MO, Wolfe I, Ceesay SJ, De Groote D, et al. Newborns develop a th1-type immune response to mycobacterium bovis bacillus calmette-guerin vaccination. J Immunol 1999; 163:2249-55; PMID:10438968
   PubMed Web of Science ®Google Scholar
• Kativhu CL, Libraty DH. A model to explain how the bacille calmette guérin (bcg) vaccine drives interleukin-12 production in neonates. PLoS One 2016; 11:e0162148; PMID:27571272; https://doi.org/10.1371/journal.pone.0162148
   PubMed Web of Science ®Google Scholar
• Mahant A, Saubi N, Eto Y, Guitart N, Gatell JM, Hanke T, Joseph J. Preclinical development of bcg.Hiva2auxo.Int, harboring an integrative expression vector, for a hiv-tb pediatric vaccine. Enhancement of stability and specific hiv-1 t-cell immunity. Hum Vaccin Immunother 2017; [epub ahead of print]; PMID:28426273;doi:10.1080/21645515.2017.1316911
   PubMed Web of Science ®Google Scholar
• Cautivo KM, Bueno SM, Cortes CM, Wozniak A, Riedel CA, Kalergis AM. Efficient lung recruitment of respiratory syncytial virusspecific th1 cells induced by recombinant bacillus calmette-guerin promotes virus clearance and protects from infection. J Immunol 2010; 185:7633-45; PMID:21084664;https://doi.org/10.4049/jimmunol.0903452
   PubMed Web of Science ®Google Scholar
• Céspedes PC, Rey-Jurado E, Espinoza JA, Rivera CA, Canedo-Marroquín G, Bueno SM, Kalergis A. A single, low dose of a cGMP recombinant BCG vaccine elicits protective T cell immunity against the human respiratory syncytial virus infection and prevents lung pathology in mice. Vaccine 2016; 35(5):757-66
   Web of Science ®Google Scholar
• Zhang J, Qian J, Ning H, Eickhoff CS, Hoft DF, Liu J. Transcriptional suppression of il-27 production by mycobacterium tuberculosis-activated p38 mapk via inhibition of ap-1 binding. J Immunol 2011; 186:5885-95; PMID:21482740; https://doi.org/10.4049/jimmunol.1003447
   PubMed Web of Science ®Google Scholar