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Human Neonatal Rotavirus Vaccine (RV3-BB) to Target Rotavirus from Birth

Julie E. Bines ... 传染病 妇产科和儿科 • 2018.02.22
• 用新型轮状病毒疫苗进行新生儿免疫接种









在符合方案人群的1,513名参与者中,安慰剂组参与者在18月龄前出现重度轮状病毒性胃肠炎的比例为5.6%(504名婴儿中的28名),新生儿程序疫苗组中的这一比例为1.4%(498名中的7名),而婴儿程序疫苗组中的这一比例为2.7%(511名中的14名)。根据这一结果,新生儿程序组的疫苗效力为75%(95%置信区间[CI],44~91;P<0.001);婴儿程序组的疫苗效力为51%(95% CI,7~76;P=0.03);合并疫苗组(新生儿程序组和婴儿程序组合并)的疫苗效力为63%(95% CI,34~80;P<0.001)。在意向性治疗分析(1,649名参与者)中观察到了类似的结果:新生儿程序组的疫苗效力为68%(95% CI,35~86;P=0.001);婴儿程序组的疫苗效力为52%(95% CI,11~76;P=0.02);合并疫苗组的疫苗效力为60%(95% CI,31~76;P<0.001)。如果根据血清免疫应答或大便中的RV3-BB排毒证明产生了疫苗应答,则新生儿程序组的83名参与者中有78名产生疫苗应答(94%),婴儿程序组的84名参与者中有83名产生疫苗应答(99%)。组间的不良事件发生率相似。施用任何1剂疫苗或安慰剂后的21日风险期内均未发生肠套叠,在婴儿程序组中第3剂疫苗施用后114日发生1例肠套叠。



在印度尼西亚按照新生儿程序或婴儿程序施用RV3-BB,结果显示RV3-BB对预防重度轮状病毒性胃肠炎有效(由比尔及梅琳达·盖茨基金会[Bill and Melinda Gates Foundation]等资助;Australian New Zealand Clinical Trials Registry注册号为ACTRN12612001282875)。


Julie E. Bines, M.D., Jarir At Thobari, Ph.D., Cahya Dewi Satria, M.D., Amanda Handley, M.P.H., Emma Watts, B.Sci., Daniel Cowley, Ph.D., Hera Nirwati, M.D., Ph.D., James Ackland, B.Sci., Jane Standish, M.B., B.S., Frances Justice, B.Sci., Gabrielle Byars, M.Bio.Med.Sci., Katherine J. Lee, Ph.D., et al.
From the RV3 Rotavirus Vaccine Program, Murdoch Children’s Research Institute (J.E.B., A.H., E.W., D.C., J.S., F.J., G.B., K.J.L., G.L.B., K.B., N.B.-S., D.P., R.F.B., C.D.K., J.P.B.), the Department of Paediatrics, University of Melbourne (J.E.B., D.C., K.J.L., G.L.B., R.F.B., C.D.K., J.P.B.), and the Department of Gastroenterology and Clinical Nutrition, Royal Children’s Hospital Melbourne (J.E.B., J.S.), Parkville, the Departments of Paediatrics and of Epidemiology and Preventive Medicine, Monash University, and the Department of Infection and Immunity, Monash Children’s Hospital, Clayton (J.P.B.), and Medicines Development for Global Health (A.H.) and Global BioSolutions (J.A.), Melbourne — all in Victoria, Australia; the Department of Pharmacology and Therapy (J.A.T.), the Pediatric Research Office, Department of Paediatrics (C.D.S., A.V.I., Y.S.), and the Department of Microbiology (H.N.), Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, and PT Bio Farma, Bandung (N.S.B.) — all in Indonesia; and the Bill and Melinda Gates Foundation, Seattle (C.D.K.). Address reprint requests to Dr. Bines at the University of Melbourne, Level 2, Royal Children’s Hospital, 50 Flemington Rd., Parkville, 3052, VIC, Australia, or at jebines@unimelb.edu.au.



1. Parashar UD, Johnson H, Steele AD, Tate JE. Health impact of rotavirus vaccination in developing countries: progress and way forward. Clin Infect Dis 2016;62:Suppl 2:S91-S95.

2. International Vaccine Access Center (IVAC). Vaccine Information Management System (VIMS) global rotavirus vaccine access report. Baltimore: Johns Hopkins Bloomberg School of Public Health, 2017 (https://www.jhsph.edu/research/centers-and-institutes/ivac/view-hub/).

3. Cherian T, Wang S, Mantel C. Rotavirus vaccines in developing countries: the potential impact, implementation challenges, and remaining questions. Vaccine 2012;30:Suppl 1:A3-A6.

4. Das JK, Bhutta ZA. Global challenges in acute diarrhea. Curr Opin Gastroenterol 2016;32:18-23.

5. Steele AD, Madhi SA, Cunliffe NA, et al. Incidence of rotavirus gastroenteritis by age in African, Asian and European children: relevance for timing of rotavirus vaccination. Hum Vaccin Immunother 2016;12:2406-2412.

6. Clark A, Sanderson C. Timing of children’s vaccinations in 45 low-income and middle-income countries: an analysis of survey data. Lancet 2009;373:1543-1549.

7. Kaye JL. Review of paediatric gastrointestinal physiology data relevant to oral drug delivery. Int J Clin Pharm 2011;33:20-24.

8. Prendergast AJ, Kelly P. Interactions between intestinal pathogens, enteropathy and malnutrition in developing countries. Curr Opin Infect Dis 2016;29:229-236.

9. Lloyd-Johnsen C, Justice F, Donath S, Bines JE. Retrospective hospital based surveillance of intussusception in children in a sentinel paediatric hospital: benefits and pitfalls for use in post-marketing surveillance of rotavirus vaccines. Vaccine 2012;30:Suppl 1:A190-A195.

10. Cameron DJ, Bishop RF, Veenstra AA, Barnes GL, Holmes IH, Ruck BJ. Pattern of shedding of two noncultivable viruses in stools of newborn babies. J Med Virol 1978;2:7-13.

11. Bishop RF, Barnes GL, Cipriani E, Lund JS. Clinical immunity after neonatal rotavirus infection: a prospective longitudinal study in young children. N Engl J Med 1983;309:72-76.

12. Bishop RF, Tzipori SR, Coulson BS, Unicomb LE, Albert MJ, Barnes GL. Heterologous protection against rotavirus-induced disease in gnotobiotic piglets. J Clin Microbiol 1986;24:1023-1028.

13. Cameron DJ, Bishop RF, Veenstra AA, Barnes GL. Noncultivable viruses and neonatal diarrhea: fifteen-month survey in a newborn special care nursery. J Clin Microbiol 1978;8:93-98.

14. Bines JE, Danchin M, Jackson P, et al. Safety and immunogenicity of RV3-BB human neonatal rotavirus vaccine administered at birth or in infancy: a randomised, double-blind, placebo-controlled trial. Lancet Infect Dis 2015;15:1389-1397.

15. BPS–Statistics Indonesia. Statistical yearbook of Indonesia. 2016 (https://www.neliti.com/publications/48410/statistical-yearbook-of-indonesia-2016).

16. Early childhood and mortality rates by province. Table A-8.1. In: Indonesia Demographic and Health Survey 2012. Jakarta, Indonesia: Statistics Indonesia, August 2013 (https://www.dhsprogram.com/publications/publication-FR275-DHS-Final-Reports.cfm).

17. Rid A, Saxena A, Baqui AH, et al. Placebo use in vaccine trials: recommendations of a WHO expert panel. Vaccine 2014;32:4708-4712.

18. Lewis K. Vesikari Clinical Severity Scoring System manual. Seattle: PATH, May 2011.

19. Coulson BS, Fowler KJ, Bishop RF, Cotton RG. Neutralizing monoclonal antibodies to human rotavirus and indications of antigenic drift among strains from neonates. J Virol 1985;54:14-20.

20. Office for Policy in Clinical Research Operations, National Institutes of Health. DAIDS adverse event grading tables. 2017 (https://rsc.tech-res.com/clinical-research-sites/safety-reporting/daids-grading-tables).

21. Clopper CJ, Pearson ES. The use of confidence or fiducial limits illustrated in the case of the binomial. Biometrika 1934;26:404-413.

22. Agtini MD, Soeharno R, Lesmana M, et al. The burden of diarrhoea, shigellosis, and cholera in North Jakarta, Indonesia: findings from 24 months surveillance. BMC Infect Dis 2005;5:89-89.

23. Nelson EAS, Bresee JS, Parashar UD, Widdowson MA, Glass RI. Rotavirus epidemiology: the Asian Rotavirus Surveillance Network. Vaccine 2008;26:3192-3196.

24. Cunliffe NA, Witte D, Ngwira BM, 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:Suppl 1:A36-A43.

25. Zaman K, Dang DA, Victor JC, et al. Efficacy of pentavalent rotavirus vaccine against severe rotavirus gastroenteritis in infants in developing countries in Asia: a randomised, double-blind, placebo-controlled trial. Lancet 2010;376:615-623.

26. Armah GE, Sow SO, Breiman RF, et al. Efficacy of pentavalent rotavirus vaccine against severe rotavirus gastroenteritis in infants in developing countries in sub-Saharan Africa: a randomised, double-blind, placebo-controlled trial. Lancet 2010;376:606-614.

27. Bhandari N, Rongsen-Chandola T, Bavdekar A, et al. Efficacy of a monovalent human-bovine (116E) rotavirus vaccine in Indian children in the second year of life. Vaccine 2014;32:Suppl 1:A110-A116.

28. Isanaka S, Guindo O, Langendorf C, et al. Efficacy of a low-cost, heat-stable oral rotavirus vaccine in Niger. N Engl J Med 2017;376:1121-1130.

29. Vesikari T, Ruuska T, Delem A, André FE. Neonatal rotavirus vaccination with RIT 4237 bovine rotavirus vaccine: a preliminary report. Pediatr Infect Dis J 1987;6:164-169.

30. Dagan R, Kassis I, Sarov B, et al. Safety and immunogenicity of oral tetravalent human-rhesus reassortant rotavirus vaccine in neonates. Pediatr Infect Dis J 1992;11:991-996.

31. Flores J, Perez-Schael I, Blanco M, et al. Reactogenicity and immunogenicity of a high-titer rhesus rotavirus-based quadrivalent rotavirus vaccine. J Clin Microbiol 1993;31:2439-2445.

32. Rippinger CM, Patton JT, McDonald SM. Complete genome sequence analysis of candidate human rotavirus vaccine strains RV3 and 116E. Virology 2010;405:201-213.

33. Nordgren J, Sharma S, Bucardo F, et al. Both Lewis and secretor status mediate susceptibility to rotavirus infections in a rotavirus genotype-dependent manner. Clin Infect Dis 2014;59:1567-1573.

34. Sun X, Guo N, Li D, et al. Binding specificity of P[8] VP8* proteins of rotavirus vaccine strains with histo-blood group antigens. Virology 2016;495:129-135.

35. Nordgren J, Nitiema LW, Ouermi D, Simpore J, Svensson L. Host genetic factors affect susceptibility to norovirus infections in Burkina Faso. PLoS One 2013;8(7):e69557-e69557.

36. Jiang J, Jiang B, Parashar U, Nguyen T, Bines J, Patel MM. Childhood intussusception: a literature review. PLoS One 2013;8(7):e68482-e68482.

37. Yih WK, Lieu TA, Kulldorff M, et al. Intussusception risk after rotavirus vaccination in U.S. infants. N Engl J Med 2014;370:503-512.

38. Angel J, Steele AD, Franco MA. Correlates of protection for rotavirus vaccines: possible alternative trial endpoints, opportunities, and challenges. Hum Vaccin Immunother 2014;10:3659-3671.

39. Siegrist C-A. Vaccine immunology. In: Plotkin SA, Orenstein WA, Offit PA eds. Vaccines. 6th ed. Philadelphia: Elsevier, 2012:14-32.

40. Cowley D, Donato CM, Roczo-Farkas S, Kirkwood CD. Emergence of a novel equine-like G3P[8] inter-genogroup reassortant rotavirus strain associated with gastroenteritis in Australian children. J Gen Virol 2016;97:403-410.

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