Intranasal norovirus vaccination shows efficacy in preventing acute gastroenteritis following a live GI.1 NoV challenge (106.5)

Abstract NoVs are a common cause of both epidemic and endemic AGE. Currently, no vaccine is available to prevent illness. Vaccination with an IN GI.1 NoV virus-like particle (VLP) vaccine (adjuvanted with chitosan and monophosphoryl lipid A) was followed by a homologous viral challenge. The trial employed a randomized, double-blind, placebo-controlled design for assessing safety, immunogenicity and efficacy against AGE and infection. Two-doses of vaccine or placebo IN 3 weeks apart were administered to healthy adults 18-49 years of age. At least 3 weeks later ~10 HID50 of a GI.1 challenge virus was administered to subjects who were then monitored for illness and infection. Two doses of the NoV VLP vaccine were administered to 90 subjects with the vaccine being well tolerated. The per protocol (PP) population was 77 of the 84 persons who completed the challenge. Of the 84, 64% of vaccinees had a >4-fold serum IgA response, none receiving placebo. In the PP analysis the incidence of AGE decreased from 69% to 37% by vaccination and infection was reduced from 82% to 61%. Efficacy against illness was 47% (95% CI, 15-67%) and against infection was 26% (95% CI, 1-36%) relative to placebo and severity of illness was also reduced. Of note, protection from NoV illness and infection correlated with the level of 50% HBGA blocking activity prior to challenge. We report that a NoV vaccine candidate can prevent AGE and that an IN-delivered vaccine can prevent illness due to an enteric pathogen.