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Hum Vaccin Immunother. 2014 Feb;10(2):505-11. doi: 10.4161/hv.27097. Epub 2013 Nov 13.

Association of serum anti-rotavirus immunoglobulin A antibody seropositivity and protection against severe rotavirus gastroenteritis: analysis of clinical trials of human rotavirus vaccine.

Author information

  • 1GlaxoSmithKline Vaccines; Wavre, Belgium.
  • 2Rotavirus Vaccine Program, PATH; Seattle, WA USA.
  • 3Initiative for Vaccine Research; World Health Organization; Seattle, WA USA.
  • 4Department of Clinical Infection; Microbiology & Immunology; Institute of Infection & Global Health; University of Liverpool; Liverpool, UK.
  • 5Medical Research Council: Respiratory and Meningeal Pathogens Research Unit & Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases; University of the Witwatersrand; Johannesburg, South Africa.
  • 6GlaxoSmithKline Pharmaceuticals Ltd.; Bangalore, India.
  • 7GlaxoSmithKline Vaccines; Philadelphia, PA USA.

Abstract

Clinical trials of the human rotavirus vaccine Rotarix™ (RV1) have demonstrated significant reductions in severe rotavirus gastroenteritis (RVGE) in children worldwide. However, no correlate of vaccine efficacy (VE) has yet been established. This paper presents 2 analyses which aimed to investigate whether serum anti-RV IgA measured by ELISA 1 or 2 mo post-vaccination can serve as a correlate of efficacy against RVGE: (1) In a large Phase III efficacy trial (Rota-037), the Prentice criteria for surrogate endpoints was applied to anti-RV IgA seropositivity 1 mo post-vaccination. These criteria determine whether a significant vaccine group effect can be predicted from the surrogate, namely seropositivity (anti-RV IgA concentration>20 U/mL); (2) Among other GSK-sponsored RV1 VE studies, 8 studies which assessed immunogenicity at 1 or 2 mo post-vaccination in all or a sub-cohort of enrolled subjects and had at least 10 RVGE episodes were included in a meta-analysis to measure the regression between clinical VE and VE predicted from immunogenicity (VE1). In Rota-037, anti-RV IgA seropositivity post-vaccination was associated with a lower incidence of any or severe RVGE, however, the proportion of vaccine group effect explained by seropositivity was only 43.6% and 32.7% respectively. This low proportion was due to the vaccine group effect observed in seronegative subjects. In the meta-analysis, the slope of the regression between clinical VE and VE1 was statistically significant. These two independent analyses support the hypothesis that post-vaccination anti-RV IgA seropositivity (antibody concentration ≥20 U/mL) may serve as a useful correlate of efficacy in clinical trials of RV1 vaccines.

KEYWORDS:

RV1; correlate of efficacy; gastroenteritis; meta-analysis; rotavirus; vaccine

PMID:
24240068
[PubMed - in process]
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