Association of serum anti-rotavirus immunoglobulin A antibody seropositivity and protection against severe rotavirus gastroenteritis: analysis of clinical trials of human rotavirus vaccine.
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.
GlaxoSmithKline Vaccines; Wavre, Belgium.
Brigitte
B
Cheuvart
Rotavirus Vaccine Program, PATH; Seattle, WA USA.
Kathleen M
KM
Neuzil
Initiative for Vaccine Research; World Health Organization; Seattle, WA USA.
A Duncan
AD
Steele
Department of Clinical Infection; Microbiology & Immunology; Institute of Infection & Global Health; University of Liverpool; Liverpool, UK.
Nigel
N
Cunliffe
Medical 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.
Shabir A
SA
Madhi
GlaxoSmithKline Pharmaceuticals Ltd.; Bangalore, India.
Naveen
N
Karkada
GlaxoSmithKline Vaccines; Philadelphia, PA USA.
Htay Htay
HH
Han
GlaxoSmithKline Vaccines; Wavre, Belgium.
Carla
C
Vinals
D000914:Antibodies, Viral / Q000097:blood*; D015415:Biomarkers; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005759:Gastroenteritis / Q000453:epidemiology* / Q000517:prevention & control*; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood*; D015994:Incidence; D007223:Infant; D008297:Male; D012401:Rotavirus / Q000276:immunology*; D012400:Rotavirus Infections / Q000453:epidemiology* / Q000276:immunology / Q000517:prevention & control*; D044967:Serum / Q000276:immunology; D013223:Statistics as Topic
D000914:Antibodies, Viral; D015415:Biomarkers; D007070:Immunoglobulin A
RV1; correlate of efficacy; gastroenteritis; meta-analysis; rotavirus; vaccine