Serum 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.