Antirotavirus IgA seroconversion rates in children who receive concomitant oral poliovirus vaccine: A secondary, pooled analysis of Phase II and III trial data from 33 countries

Autoři: Julia M. Baker aff001;  Jacqueline E. Tate aff002;  Juan Leon aff003;  Michael J. Haber aff004;  Benjamin A. Lopman aff001
Působiště autorů: Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, United States of America aff001;  Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America aff002;  Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, Georgia, United States of America aff003;  Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia, United States of America aff004
Vyšlo v časopise: Antirotavirus IgA seroconversion rates in children who receive concomitant oral poliovirus vaccine: A secondary, pooled analysis of Phase II and III trial data from 33 countries. PLoS Med 16(12): e32767. doi:10.1371/journal.pmed.1003005
Kategorie: Research Article



Despite the success of rotavirus vaccines over the last decade, rotavirus remains a leading cause of severe diarrheal disease among young children. Further progress in reducing the burden of disease is inhibited, in part, by vaccine underperformance in certain settings. Early trials suggested that oral poliovirus vaccine (OPV), when administered concomitantly with rotavirus vaccine, reduces rotavirus seroconversion rates after the first rotavirus dose with modest or nonsignificant interference after completion of the full rotavirus vaccine course. Our study aimed to identify a range of individual-level characteristics, including concomitant receipt of OPV, that affect rotavirus vaccine immunogenicity in high- and low-child-mortality settings, controlling for individual- and country-level factors. Our central hypothesis was that OPV administered concomitantly with rotavirus vaccine reduced rotavirus vaccine immunogenicity.

Methods and findings

Pooled, individual-level data from GlaxoSmithKline’s Phase II and III clinical trials of the monovalent rotavirus vaccine (RV1), Rotarix, were analyzed, including 7,280 vaccinated infants (5–17 weeks of age at first vaccine dose) from 22 trials and 33 countries/territories (5 countries/territories with high, 13 with moderately low, and 15 with very low child mortality). Two standard markers for immune response were examined including antirotavirus immunoglobulin A (IgA) seroconversion (defined as the appearance of serum antirotavirus IgA antibodies in subjects initially seronegative) and serum antirotavirus IgA titer, both collected approximately 4–12 weeks after administration of the last rotavirus vaccine dose. Mixed-effect logistic regression and mixed-effect linear regression of log-transformed data were used to identify individual- and country-level predictors of seroconversion (dichotomous) and antibody titer (continuous), respectively. Infants in high-child-mortality settings had lower odds of seroconverting compared with infants in low-child-mortality settings (odds ratio [OR] = 0.48, 95% confidence interval [CI] 0.43–0.53, p < 0.001). Similarly, among those who seroconverted, infants in high-child-mortality settings had lower IgA titers compared with infants in low-child-mortality settings (mean difference [β] = 0.83, 95% CI 0.77–0.90, p < 0.001). Infants who received OPV concomitantly with both their first and their second doses of rotavirus vaccine had 0.63 times the odds of seroconverting (OR = 0.63, 95% CI 0.47–0.84, p = 0.002) compared with infants who received OPV but not concomitantly with either dose. In contrast, among infants who seroconverted, OPV concomitantly administered with both the first and second rotavirus vaccine doses was found to be positively associated with antirotavirus IgA titer (β = 1.28, 95% CI 1.07–1.53, p = 0.009). Our findings may have some limitations in terms of generalizability to routine use of rotavirus vaccine because the analysis was limited to healthy infants receiving RV1 in clinical trial settings.


Our findings suggest that OPV given concomitantly with RV1 was a substantial contributor to reduced antirotavirus IgA seroconversion, and this interference was apparent after the second vaccine dose of RV1, as with the original clinical trials that our reanalysis is based on. However, our findings do suggest that the forthcoming withdrawal of OPV from the infant immunization schedule globally has the potential to improve RV1 performance.

Klíčová slova:

Antigens – Death rates – Child health – Infants – Rotavirus – Rotavirus infection – Serology – Vaccines


1. Troeger C, Khalil IA, Rao PC, Cao S, Blacker BF, Ahmed T, et al. Rotavirus Vaccination and the Global Burden of Rotavirus Diarrhea Among Children Younger Than 5 Years. JAMA Pediatr. 2018;172: 958. doi: 10.1001/jamapediatrics.2018.1960 30105384

2. Tate JE, Burton AH, Boschi-Pinto C, Parashar UD. Global, Regional, and National Estimates of Rotavirus Mortality in Children <5 Years of Age, 2000–2013. Clin Infect Dis. 2016;62: S96–S105. doi: 10.1093/cid/civ1013 27059362

3. Centers for Disease Control and Prevention [Internet]. Atlanta, GA: Centers for Diesease Control and Prevention; [cited 2017 Aug 20]. Rotavirus and the Vaccine (Drops) to Prevent It. Available from:

4. Velázquez FR, Matson DO, Calva JJ, Guerrero ML, Morrow AL, Carter-Campbell S, et al. Rotavirus Infection in Infants as Protection against Subsequent Infections. N Engl J Med. 1996;335: 1022–1028. doi: 10.1056/NEJM199610033351404 8793926

5. Gurwith M, Wenman W, Hinde D, Feltham S, Greenberg H. A prospective study of rotavirus infection in infants and young children. J Infect Dis. 1981;144: 218–224. doi: 10.1093/infdis/144.3.218 6268713

6. Gladstone BP, Ramani S, Mukhopadhya I, Muliyil J, Sarkar R, Rehman AM, et al. Protective Effect of Natural Rotavirus Infection in an Indian Birth Cohort. N Engl J Med. 2011;365: 337–346. doi: 10.1056/NEJMoa1006261 21793745

7. Santosham M, Steele D. Rotavirus Vaccines—A New Hope. N Engl J Med. 2017;376: 1170–1172. doi: 10.1056/NEJMe1701347 28328339

8. World Health Organization [Internet]. Geneva, Switzerland: World Health Organization; 2016 Jun 3 [cited 2019 Feb 3]. Immunization, Vaccines and Biologicals: Rotavirus [Internet]. Available from:

9. Vesikari T, Karvonen A, Prymula R, Schuster V, Tejedor J, Cohen R, et al. Efficacy of human rotavirus vaccine against rotavirus gastroenteritis during the first 2 years of life in European infants: randomised, double-blind controlled study. The Lancet. 2007;370: 1757–1763. doi: 10.1016/S0140-6736(07)61744-9

10. Vesikari T, Matson DO, Dennehy P, Van Damme P, Santosham M, Rodriguez Z, et al. Safety and Efficacy of a Pentavalent Human–Bovine (WC3) Reassortant Rotavirus Vaccine. N Engl J Med. 2006;354: 23–33. doi: 10.1056/NEJMoa052664 16394299

11. Nelson EAS, Glass RI. Rotavirus: realising the potential of a promising vaccine. The Lancet. 2010;376: 568–570. doi: 10.1016/S0140-6736(10)60896-3

12. Rota Council: Rotavirus Orgnaization of Technical Allies. Rotavirus Deaths & Rotavirus Vaccine Introduction Maps [Internet]. [cited 16 Oct 2016]. Available from:

13. Jiang V, Jiang B, Tate J, Parashar UD, Patel MM. Performance of rotavirus vaccines in developed and developing countries. Hum Vaccin. 2010;6: 532–542. doi: 10.4161/hv.6.7.11278 20622508

14. Linhares AC, Velázquez FR, Pérez-Schael I, Sáez-Llorens X, Abate H, Espinoza F, 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. The Lancet. 2008;371: 1181–1189. doi: 10.1016/S0140-6736(08)60524-3.

15. Ruiz-Palacios GM, Pérez-Schael I, Velázquez FR, Abate H, Breuer T, Clemens SC, et al. Safety and Efficacy of an Attenuated Vaccine against Severe Rotavirus Gastroenteritis. N Engl J Med. 2006;354. doi: 10.1056/NEJMoa060442

16. Platts-Mills JA, Amour C, Gratz J, Nshama R, Walongo T, Mujaga B, et al. Impact of Rotavirus Vaccine Introduction and Postintroduction Etiology of Diarrhea Requiring Hospital Admission in Haydom, Tanzania, a Rural African Setting. Clin Infect Dis. 2017;65: 1144–1151. doi: 10.1093/cid/cix494 28575304

17. Operario DJ, Platts-Mills JA, Nadan S, Page N, Seheri M, Mphahlele J, et al. Etiology of Severe Acute Watery Diarrhea in Children in the Global Rotavirus Surveillance Network Using Quantitative Polymerase Chain Reaction. J Infect Dis. 2017;216: 220–227. doi: 10.1093/infdis/jix294 28838152

18. World Health Organization. Rotavirus vaccines. WHO position paper–January 2013. Releve Epidemiol Hebd. 2013;88: 49–64.

19. Jonesteller CL, Burnett E, Yen C, Tate JE, Parashar UD. Effectiveness of Rotavirus Vaccination: A Systematic Review of the First Decade of Global Postlicensure Data, 2006–2016. Clin Infect Dis. 2017;65: 840–850. doi: 10.1093/cid/cix369 28444323

20. Soares-Weiser K, MacLehose H, Bergman H, Ben-Aharon I, Nagpal S, Goldberg E, et al. Vaccines for preventing rotavirus diarrhoea: vaccines in use. In: The Cochrane Collaboration, editor. Cochrane Database of Systematic Reviews. Chichester, UK: John Wiley & Sons; 2012. Available from:

21. Patel M, Glass RI, Jiang B, Santosham M, Lopman B, Parashar U. A Systematic Review of Anti-Rotavirus Serum IgA Antibody Titer as a Potential Correlate of Rotavirus Vaccine Efficacy. J Infect Dis. 2013;208: 284–294. doi: 10.1093/infdis/jit166 23596320

22. Patel M, Shane AL, Parashar UD, Jiang B, Gentsch JR, Glass RI. Oral Rotavirus Vaccines: How Well Will They Work Where They Are Needed Most? J Infect Dis. 2009;200: S39–S48. doi: 10.1086/605035 19817613

23. Parker EP, Ramani S, Lopman BA, Church JA, Iturriza-Gómara M, Prendergast AJ, et al. Causes of impaired oral vaccine efficacy in developing countries. Future Microbiol. 2018;13: 97–118. doi: 10.2217/fmb-2017-0128 29218997

24. Velasquez DE, Parashar U, Jiang B. Decreased performance of live attenuated, oral rotavirus vaccines in low-income settings: causes and contributing factors. Expert Rev Vaccines. 2017; 1–17. doi: 10.1080/14760584.2018.1418665 29252042

25. Clarke E, Desselberger U. Correlates of protection against human rotavirus disease and the factors influencing protection in low-income settings. Mucosal Immunol. 2015;8: 1–17. doi: 10.1038/mi.2014.114 25465100

26. Lee B, Dickson DM, deCamp AC, Ross Colgate E, Diehl SA, Uddin MI, et al. Histo–Blood Group Antigen Phenotype Determines Susceptibility to Genotype-Specific Rotavirus Infections and Impacts Measures of Rotavirus Vaccine Efficacy. J Infect Dis. 2018;217: 1399–1407. doi: 10.1093/infdis/jiy054 29390150

27. Payne DC, Currier RL, Staat MA, Sahni LC, Selvarangan R, Halasa NB, et al. Epidemiologic Association Between FUT2 Secretor Status and Severe Rotavirus Gastroenteritis in Children in the United States. JAMA Pediatr. 2015;169: 1040. doi: 10.1001/jamapediatrics.2015.2002 26389824

28. Kambhampati A, Payne DC, Costantini V, Lopman BA. Host Genetic Susceptibility to Enteric Viruses: A Systematic Review and Metaanalysis. Clin Infect Dis. 2016;62: 11–18. doi: 10.1093/cid/civ873 26508510

29. Naylor C, Lu M, Haque R, Mondal D, Buonomo E, Nayak U, et al. Environmental Enteropathy, Oral Vaccine Failure and Growth Faltering in Infants in Bangladesh. EBioMedicine. 2015;2: 1759–1766. doi: 10.1016/j.ebiom.2015.09.036 26870801

30. Bresee JS, Glass RI, Ivanoff B, Gentsch JR. Current status and future priorities for rotavirus vaccine development, evaluation and implementation in developing countries. Vaccine. 1999;17: 2207–2222. doi: 10.1016/s0264-410x(98)00376-4 10403588

31. World Health Organization [Internet]. Geneva, Switzerland: World Health Organization; 2018 [cited 2019 Jan 30]. Summary of WHO Position Papers- Recommended Routine Immunizations for Children. Available from:

32. Emperador DM, Velasquez DE, Estivariz CF, Lopman B, Jiang B, Parashar U, et al. Interference of Monovalent, Bivalent, and Trivalent Oral Poliovirus Vaccines on Monovalent Rotavirus Vaccine Immunogenicity in Rural Bangladesh. Clin Infect Dis. 2016;62: 150–156. doi: 10.1093/cid/civ807 26349548

33. Steele AD, De Vos B, Tumbo J, Reynders J, Scholtz F, Bos P, et al. Co-administration study in South African infants of a live-attenuated oral human rotavirus vaccine (RIX4414) and poliovirus vaccines. Vaccine. 2010;28: 6542–6548. doi: 10.1016/j.vaccine.2008.08.034 18786585

34. Li R, Huang T, Li Y, Wang L-H, Tao J, Fu B, et al. Immunogenicity and reactogenicity of the human rotavirus vaccine, RIX4414 oral suspension, when co-administered with routine childhood vaccines in Chinese infants. Hum Vaccines Immunother. 2016;12: 785–793. doi: 10.1080/21645515.2015.1085143 27149266

35. Ramani S, Mamani N, Villena R, Bandyopadhyay AS, Gast C, Sato A, et al. Rotavirus Serum IgA Immune Response in Children Receiving Rotarix Coadministered With bOPV or IPV: Pediatr Infect Dis J. 2016;35: 1137–1139. doi: 10.1097/INF.0000000000001253 27254033

36. Zaman K, Sack DA, Yunus M, Arifeen SE, Podder G, Azim T, et al. Successful co-administration of a human rotavirus and oral poliovirus vaccines in Bangladeshi infants in a 2-dose schedule at 12 and 16 weeks of age. Vaccine. 2009;27: 1333–1339. doi: 10.1016/j.vaccine.2008.12.059 19162114

37. Patel M, Steele AD, Parashar UD. Influence of oral polio vaccines on performance of the monovalent and pentavalent rotavirus vaccines. Vaccine. 2012;30: A30–A35. doi: 10.1016/j.vaccine.2011.11.093 22520134

38. World Health Organization. Polio vaccines: WHO position paper, March 2016–recommendations. Vaccine. 2017;35: 1197–1199. doi: 10.1016/j.vaccine.2016.11.017 27894720

39. GlaxoSmithKline. Highlights of prescribing information [Internet]. Brentford, UK: GloxoSmithKline; 2016 [cited 2017 Mar 30]. Available from:

40. World Health Organization. List of Member States by WHO region and mortality stratum [Internet]. World Health Organization; [cited 2017 Aug 12]. Available from:

41. UNICEF [Internet]. The UN Inter-agency Group for Child Mortality Estimation. New York: UNICEF; 2015 Sep 9 [cited 2019 Jan 18]. Available from:

42. World Bank Open Data [Internet]. Washington, DC: The World Bank; 2018 [cited 2018 Sep 28]. Available from:

43. Taiwan (Taiwan Province of China) GDP per Capita (Current Prices, US Dollars) Statistics [Internet]. Economy Watch; 2018 Nov 28 [cited 2018 Nov28]. Available from:

44. Mortality rate, under-5 (per 1,000 live births) [Internet]. Washington, DC: The World Bank; 2018 [cited 2018 Sep 28]. Available from:

45. Hong Kong- Under-five mortality rate [Internet]. Washington, DC: Knoema; [cited 28 Nov 2018]. Available from:

46. Wu JC-L, Chiang T-L. Comparing Child Mortality in Taiwan and Selected Industrialized Countries. J Formos Med Assoc. 2007;106: 177–180. doi: 10.1016/S0929-6646(09)60237-0 17339165

47. Zaccaro DJ, Wagener DK, Whisnant CC, Staats HF. Evaluation of vaccine-induced antibody responses: impact of new technologies. Vaccine. 2013;31: 2756–2761. doi: 10.1016/j.vaccine.2013.03.065 23583812

48. Beyer WEP, Palache AM, Lüchters G, Nauta J, Osterhaus ADME. Seroprotection rate, mean fold increase, seroconversion rate: which parameter adequately expresses seroresponse to influenza vaccination? Virus Res. 2004;103: 125–132. doi: 10.1016/j.virusres.2004.02.024 15163500

49. GlaxoSmithKline. Safety Study Report Rota-023 (444563/023) [Internet]. GlaxoSmithKline; 2004 [cited 2019 May 17]. Available from:

50. GlaxoSmithKline. Clinical Study Report for Study 102248 (Rota-037) [Internet]. GlaxoSmithKline; 2009 [cited 2019 May 17]. Available from:

51. ThermoFisher Scientific [Internet]. Waltham, MA: Thermo Fisher Scientific; [cited 2019 Feb 14]. Overview of ELISA. Available from:

52. Wang H, Moon S, Wang Y, Jiang B. Multiple virus infection alters rotavirus replication and expression of cytokines and Toll-like receptors in intestinal epithelial cells. Virus Res. 2012;167: 48–55. doi: 10.1016/j.virusres.2012.04.001 22497974

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