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

J Infect Dis. 2016 Jun 1;213(11):1678-85. doi: 10.1093/infdis/jiw023. Epub 2016 Jan 27.

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.

Publication types

  • Clinical Trial, Phase IV
  • Randomized Controlled Trial

MeSH terms

  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • Female
  • Ghana
  • Humans
  • Immunity, Maternally-Acquired
  • Immunization Schedule*
  • Immunoglobulin A / blood
  • Immunoglobulin A / immunology
  • Infant
  • Male
  • Rotavirus Vaccines / administration & dosage*
  • Rotavirus Vaccines / immunology

Substances

  • Antibodies, Viral
  • Immunoglobulin A
  • Rotavirus Vaccines

Associated data

  • ClinicalTrials.gov/NCT01575197