Abstract

ABSTRACTSerum rotavirus IgA responses are an imperfect non-mechanistic correlate of protection, and the lack of an accurate serological marker is a challenge to the development of new rotavirus vaccines. Serological responses to rotavirus NSP2 occur following wild-type infection; however, it is unknown if serological responses to NSP2 occur following administration of rotavirus vaccines. The phase IIa immunogenicity trial of RV3-BB provided an opportunity to investigate the serological responses to NSP2 following vaccination. Healthy, full-term babies (n = 96) were previously recruited as part of a phase IIa safety and immunogenicity trial in Dunedin, New Zealand between January 2012 and April 2014. Participants received three doses of oral RV3-BB vaccine with the first dose given at 0–5 days after birth (neonatal schedule), or the first dose given at about 8 weeks after birth (infant schedule), or to receive placebo (placebo schedule). Serum IgA and IgG antibody responses to total RV3-BB and NSP2 protein (RV3-BB) were assessed using ELISA. Despite significant serum IgA response against total RV3-BB, we were unable to demonstrate a significant serological response to NSP2 in participants receiving RV3-BB when compared to placebo. Heterotypic antibodies against multiple NSP2 genotypes were detected following RV3-BB vaccination. Our data demonstrates that while serological responses to NSP2 were detectable in a subset of participants, it is a less useful marker when compared to total rotavirus serum IgA response.

Highlights

  • Rotavirus is the most common cause of severe diarrhoea in children under 5 years of age

  • The proportion of participants with seroconversion to total RV3-BB are higher when compared to RV3-BB NSP2 protein

  • In the infant vaccine schedule, serum IgA responses to NSP2 were detected in 9/27 (33.3%) participants compared to 7/32 (21.9%) in the placebo

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Summary

Introduction

Rotavirus is the most common cause of severe diarrhoea in children under 5 years of age. ROTAVAC (Bharat Biotech, Hyderabad, India) are WHO prequalified and available in more than 100 countries. New rotavirus vaccines are in development to address concerns regarding reduced efficacy in low-income countries[1,2] and supply.[3] One candidate is the human neonatal vaccine RV3-BB, based on a naturally attenuated neonatal G3P[6] rotavirus strain. The intrinsic characteristics of the RV3-BB vaccine makes it ideal for a birth dose administration schedule which may have benefits to provide early protection in low-income settings.[4,5]. IgM, IgG and IgA antibodies against rotavirus appear in serum and mucosal secretions.[6] Several rotavirus structural proteins are immunogenic in humans, including the viral proteins (VP) VP6, VP2, VP7 and VP4.7-10

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