Evaluation of Serum Antibodies as Correlates of Protection Against Norovirus Infection and Disease.

BACKGROUND

Norovirus is a major cause of acute gastroenteritis. Several vaccines are in development. Identifying a reliable immunological correlate of protection (CoP) would aid vaccine development and evaluation; however, no strong CoP has been established to date.

METHODS

We evaluated the relationships between prechallenge genogroup I, genotype 1 (GI.1) and GII.4 norovirus antibodies and clinical outcomes in two human vaccine-challenge studies. We analyzed genotype-specific histo-blood group antigen blocking titers, serum IgA and IgG, and total antibody ELISA. We used Bayesian regression models to assess relationships between antibody levels and protection against infection, illness, and disease severity.

RESULTS

Associations between antibody titers and protection were generally weak, and varied by genotype and vaccination status. GI.1 antibodies showed the strongest relationships, particularly among vaccinated participants, whereas naturally acquired GI.1 antibodies in unvaccinated individuals were weakly or not associated with protection. In contrast, GII.4 antibodies exhibited weak and inconsistent relationships among vaccinated participants, while unvaccinated participants showed only modest and more stable positive associations.

CONCLUSIONS

Currently measured serum antibodies do not provide reliable and robust estimates of protection against norovirus clinical outcomes in all settings. Immune markers beyond serum antibody titers should be evaluated to identify more robust correlates of protection for norovirus.