Postdose 3 G1 serum neutralizing antibody as correlate of protection for pentavalent rotavirus vaccine

ABSTRACT

Although clinical trials of the pentavalent rotavirus vaccine (RotaTeq®, RV5) have demonstrated efficacy against RV gastroenteritis (RGE) in low and high-income settings, a clear correlate of protection or a measure of immune response that could predict efficacy has yet to be identified. This is the first time that immunogenicity data with both serum neutralized antibody (SNA) titers and anti-RV IgA titers from several clinical efficacy trials were pooled to provide a unique context for evaluating the correlation between immunogenicity and RGE risk or efficacy of RV5. The correlation between immunogenicity and RGE risk is evaluated with data at the individual subject level. The analyses show that higher Postdose 3 (PD3) G1 SNA titers are associated with lower odds of contracting any RGE. The correlation between immunogenicity and efficacy is assessed using aggregated population level data, which shows higher efficacy associated with higher PD3 G1 SNA geometric mean titer (GMT) ratio (between RV5 and placebo) and PD3 serum anti-RV IgA GMT ratio. Among high-income countries, efficacy plateaus over the range of PD3 G1 SNA GMT ratios and PD3 serum anti-RV IgA GMT ratios. From both individual- and population-level analyses, PD3 G1 SNA titers correlated most closely with the RGE risk or efficacy for RV5.

KEYWORDS:

• correlation of protection
• geometric mean titer (GMT)
• immunogenicity
• pentavalent rotavirus vaccine (RV5)
• rotavirus gastroenteritis (RGE)

Disclosure of potential conflicts of interest

This study was funded by Merck & Co., Inc., Kenilworth, NJ, USA (sponsor). This study was designed, executed, and analyzed by the sponsor. All co-authors approved the final version of the manuscript.

Employees of the sponsor (indicated on the title page) may own stock or stock options in the company.

Funding

Funding for this research was provided by Merck & Co., Inc., Kenilworth, NJ, USA.