• Efficacy of a Low-Cost, Heat-Stable Oral Rotavirus Vaccine in Niger

      Isanaka, S; Guindo, O; Langendorf, C; Matar Seck, A; Plikaytis, BD; Sayinzoga-Makombe, N; McNeal, MM; Meyer, N; Adehossi, E; Djibo, A; et al. (Massachusetts Medical Society, 2017-03-23)
      Background Each year, rotavirus gastroenteritis is responsible for about 37% of deaths from diarrhea among children younger than 5 years of age worldwide, with a disproportionate effect in sub-Saharan Africa. Methods We conducted a randomized, placebo-controlled trial in Niger to evaluate the efficacy of a live, oral bovine rotavirus pentavalent vaccine (BRV-PV, Serum Institute of India) to prevent severe rotavirus gastroenteritis. Healthy infants received three doses of the vaccine or placebo at 6, 10, and 14 weeks of age. Episodes of gastroenteritis were assessed through active and passive surveillance and were graded on the basis of the score on the Vesikari scale (which ranges from 0 to 20, with higher scores indicating more severe disease). The primary end point was the efficacy of three doses of vaccine as compared with placebo against a first episode of laboratory-confirmed severe rotavirus gastroenteritis (Vesikari score, ≥11) beginning 28 days after dose 3. Results Among the 3508 infants who were included in the per-protocol efficacy analysis, there were 31 cases of severe rotavirus gastroenteritis in the vaccine group and 87 cases in the placebo group (2.14 and 6.44 cases per 100 person-years, respectively), for a vaccine efficacy of 66.7% (95% confidence interval [CI], 49.9 to 77.9). Similar efficacy was seen in the intention-to-treat analyses, which showed a vaccine efficacy of 69.1% (95% CI, 55.0 to 78.7). There was no significant between-group difference in the risk of adverse events, which were reported in 68.7% of the infants in the vaccine group and in 67.2% of those in the placebo group, or in the risk of serious adverse events (in 8.3% in the vaccine group and in 9.1% in the placebo group); there were 27 deaths in the vaccine group and 22 in the placebo group. None of the infants had confirmed intussusception. Conclusions Three doses of BRV-PV, an oral rotavirus vaccine, had an efficacy of 66.7% against severe rotavirus gastroenteritis among infants in Niger. (Funded by Médecins sans Frontières Operational Center and the Kavli Foundation; ClinicalTrials.gov number, NCT02145000 .).
    • A mixture model to assess the the immunogenicity of an oral rotavirus vaccine among healthy infants in Niger

      Hitchings, MDT; Cummings, DAT; Grais, RFF; Isanaka, S (Elsevier, 2020-11-05)
      Analysis of immunogenicity data is a critical component of vaccine development, providing a biological basis to support any observed protection from vaccination. Conventional methods for analyzing immunogenicity data use either post-vaccination titer or change in titer, often defined as a binary variable using a threshold. These methods are simple to implement but can be limited especially in populations experiencing natural exposure to the pathogen. A mixture model can overcome the limitations of the conventional approaches by jointly modeling the probability of an immune response and the level of the immune marker among those who respond. We apply a mixture model to analyze the immunogenicity of an oral, pentavalent rotavirus vaccine in a cohort of children enrolled into a placebo-controlled vaccine efficacy trial in Niger. Among children with undetectable immunoglobulin A (IgA) at baseline, vaccinated children had 5.2-fold (95% credible interval (CrI) 3.7, 8.3) higher odds of having an IgA response than placebo children, but the mean log IgA among vaccinated responders was 0.9-log lower (95% CrI 0.6, 1.3) than among placebo responders. This result implies that the IgA response generated by vaccination is weaker than that generated by natural infection. Multivariate logistic regression of seroconversion defined by ≥ 3-fold rise in IgA similarly found increased seroconversion among vaccinated children, but could not demonstrate lower IgA among those who seroresponded. In addition, we found that the vaccine was less immunogenic among children with detectable IgA pre-vaccination, and that pre-vaccination infant serum IgG and mother’s breast milk IgA modified the vaccine immunogenicity. Increased maternal antibodies were associated with weaker IgA response in placebo and vaccinated children, with the association being stronger among vaccinated children. The mixture model is a powerful and flexible method for analyzing immunogenicity data and identifying modifiers of vaccine response and independent predictors of immune response.
    • Safety of a heat-stable rotavirus vaccine among children in Niger: Data from a phase 3, randomized, double-blind, placebo-controlled trial

      Coldiron, ME; Guindo, O; Makarimi, R; Soumana, I; Matar Seck, A; Garba, S; Macher, E; Isanaka, S; Grais, RFF (Elsevier, 2018-05-08)
      Rotavirus remains a major cause of diarrhea among children under 5 years of age. The efficacy of RotaSIIL, a pentavalent rotavirus vaccine, was shown in an event-driven trial in Niger. We describe the two-year safety follow-up of this trial.