A Randomized, Controlled Trial of the Impact of Alternative Dosing Schedules on the Immune Response to Human Rotavirus Vaccine in Rural Ghanaian Infants

George Armah, Kristen D C Lewis, Margaret M Cortese, Umesh D Parashar, Akosua Ansah, Lauren Gazley, John C Victor, Monica M McNeal, Fred Binka, A Duncan Steele, George Armah, Kristen D C Lewis, Margaret M Cortese, Umesh D Parashar, Akosua Ansah, Lauren Gazley, John C Victor, Monica M McNeal, Fred Binka, A Duncan Steele

Abstract

Background: The recommended schedule for receipt of 2-dose human rotavirus vaccine (HRV) coincides with receipt of the first and second doses of diphtheria, pertussis, and tetanus vaccine (ie, 6 and 10 weeks of age, respectively). Alternative schedules and additional doses of HRV have been proposed and may improve vaccine performance in low-income countries.

Methods: In this randomized trial in rural Ghana, HRV was administered at ages 6 and 10 weeks (group 1), 10 and 14 weeks (group 2), or 6, 10, and 14 weeks (group 3). We compared serum antirotavirus immunoglobulin A (IgA) seroconversion (≥20 U/mL) and geometric mean concentrations (GMCs) between group 1 and groups 2 and 3.

Results: Ninety-three percent of participants (424 of 456) completed the study per protocol. In groups 1, 2, and 3, the IgA seroconversion frequencies among participants with IgA levels of <20 U/mL at baseline were 28.9%, 37.4%, and 43.4%, respectively (group 1 vs group 3, P = .014; group 1 vs group 2, P = .163). Postvaccination IgA GMCs were 22.1 U/mL, 26.5 U/mL, and 32.6 U/mL in groups 1, 2, and 3, respectively (group 1 vs group 3, P = .038; group 1 vs group 2, P = .304).

Conclusions: A third dose of HRV resulted in increased seroconversion frequencies and GMCs, compared with 2 doses administered at 6 and 10 weeks of age. Since there is no correlate of protection, a postmarketing effectiveness study is required to determine whether the improvement in immune response translates into a public health benefit in low-income countries.

Clinical trials registration: NCT015751.

Trial registration: ClinicalTrials.gov NCT01575197.

Keywords: developing countries; immunization schedules; immunogenicity; infant; randomized controlled trial; rotavirus; rotavirus vaccines; vaccines.

© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

Figures

Figure 1.
Figure 1.
Study profile. Abbreviations: PPE, per-protocol evaluation; SAE, serious adverse event.

References

    1. World Health Organization. Rotavirus vaccines WHO position paper. Wkly Epidemiol Rec 2007; 82:285–96.
    1. Tate JE, Burton AH, Boschi-Pinto C, Steele AD, Duque J, Parashar UD. 2008 estimate of worldwide rotavirus-associated mortality in children younger than 5 years before the introduction of universal rotavirus vaccination programmes: a systematic review and meta-analysis. Lancet Infect Dis 2012; 12:136–41.
    1. Armah GE, Breiman RF, Tapia MD et al. . Immunogenicity of the pentavalent rotavirus vaccine in African infants. Vaccine 2012; 30(suppl 1):A86–93.
    1. Armah GE, Kapikian AZ, Vesikari T et al. . 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; 208:423–31.
    1. Binka FN, Anto FK, Oduro AR et al. . Incidence and risk factors of paediatric rotavirus diarrhoea in northern Ghana. Trop Med Int Health 2003; 8:840–6.
    1. Armah GE, Mingle JA, Dodoo AK et al. . Seasonality of rotavirus infection in Ghana. Ann Trop Paediatr 1994; 14:223–9.
    1. Mwenda JM, Ntoto KM, Abebe A et al. . Burden and epidemiology of rotavirus diarrhea in selected African countries: preliminary results from the African Rotavirus Surveillance Network. J Infect Dis 2010; 202(suppl):S5–11.
    1. Vesikari T, Matson DO, Dennehy P et al. . Safety and efficacy of a pentavalent human-bovine (WC3) reassortant rotavirus vaccine. N Engl J Med 2006; 354:23–33.
    1. Clark HF, Bernstein DI, Dennehy PH et al. . Safety, efficacy, and immunogenicity of a live, quadrivalent human-bovine reassortant rotavirus vaccine in healthy infants. J Pediatr 2004; 144:184–90.
    1. Madhi SA, Cunliffe NA, Steele D et al. . Effect of human rotavirus vaccine on severe diarrhea in African infants. N Engl J Med 2010; 362:289–98.
    1. Shin S, Anh DD, Zaman K et al. . Immunogenicity of the pentavalent rotavirus vaccine among infants in two developing countries in Asia, Bangladesh and Vietnam. Vaccine 2012; 30(suppl 1):A106–13.
    1. Ali SA, Kazi AM, Cortese MM et al. . Impact of different dosing schedules on the immunogenicity of the human rotavirus vaccine in infants in Pakistan: a randomized trial. J Infect Dis 2014; 210:1772–9.
    1. Ruiz-Palacios GM, Perez-Schael I, Velazquez FR et al. . Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis. N Engl J Med 2006; 354:11–22.
    1. 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; 376:606–14.
    1. 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; 376:615–23.
    1. Tapia MD, Armah G, Breiman RF et al. . Secondary efficacy endpoints of the pentavalent rotavirus vaccine against gastroenteritis in sub-Saharan Africa. Vaccine 2012; 30(suppl 1):A79–85.
    1. Zaman K, Sack DA, Yunus M 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; 27:1333–9.
    1. Wood D. WHO informal consultation on quality, safety and efficacy specifications for live attenuated rotavirus vaccines Mexico City, Mexico, 8-9 February 2005. Vaccine 2005; 23:5478–87.
    1. Steele AD, De VB, Tumbo J et al. . Co-administration study in South African infants of a live-attenuated oral human rotavirus vaccine (RIX4414) and poliovirus vaccines. Vaccine 2010; 28:6542–8.
    1. Parashar UD, Glass RI. Rotavirus vaccines--early success, remaining questions. N Engl J Med 2009; 360:1063–5.
    1. Madhi SA, Kirsten M, Louw C et al. . 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(suppl 1):A44–51.
    1. Gentsch JR, Glass RI, Woods P et al. . Identification of group A rotavirus gene 4 types by polymerase chain reaction. J Clin Microbiol 1992; 30:1365–73.
    1. Gouvea V, Glass RI, Woods P et al. . Polymerase chain reaction amplification and typing of rotavirus nucleic acid from stool specimens. J Clin Microbiol 1990; 28:276–82.
    1. Ward RL, Bernstein DI, Shukla R et al. . Protection of adults rechallenged with a human rotavirus. J Infect Dis 1990; 161:440–5.
    1. Bernstein DI, Smith VE, Sherwood JR et al. . Safety and immunogenicity of live, attenuated human rotavirus vaccine 89-12. Vaccine 1998; 16:381–7.
    1. Vesikari T, Karvonen A, Korhonen T et al. . Safety and immunogenicity of RIX4414 live attenuated human rotavirus vaccine in adults, toddlers and previously uninfected infants. Vaccine 2004; 22:2836–42.
    1. 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):A36–43.
    1. Anh DD. National Development and Licensure of a Human Monovalent Rotavirus Vaccine (ROTAVIN-M1) in Vietnam. 2012.
    1. Anderson EJ. Rotavirus vaccines: viral shedding and risk of transmission. Lancet Infect Dis 2008; 8:642–9.
    1. Angel J, Franco MA, Greenberg HB. Rotavirus immune responses and correlates of protection. Curr Opin Virol 2012; 2:419–25.
    1. Cheuvart B, Neuzil KM, Steele AD et al. . Association of serum anti-rotavirus immunoglobulin A antibody seropositivity and protection against severe rotavirus gastroenteritis: analysis of clinical trials of human rotavirus vaccine. Hum Vaccin Immunother 2014; 10:505–11.
    1. World Health Organization. Meeting of the immunization Strategic Advisory Group of Experts, April 2009 - Conclusions and recommendations. Wkly Epidemiol Rec 2009; 84:220–36.

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel