78. Oral Norovirus Vaccination in Humans Induces Plasmablast B-Cell Expansion and Follicular T-Cell Activation Comparable to Natural Infection

BACKGROUND: Norovirus (NoV) is a common cause of acute gastroenteritis, but no vaccines are currently licensed. Vaxart is developing an oral tableted NoV vaccine that induces both systemic and mucosal immune responses. METHODS: Two separate clinical studies were conducted to evaluate the safety and immunogenicity of an oral NoV vaccine and NoV infection. The first study investigated an oral tablet vaccine based on a recombinant adenovirus vector expressing NoV VP1 (rAd-VP1). In the second study, a controlled NoV infection (Norwalk virus) was performed using a strain isolated and purified from an infected subject. Serum and PBMCs were collected pre- and post-immunization/infection. Serum immune responses were assessed using IgG/IgA ELISAs and blocking titer (BT50) assays. Cellular immune responses were evaluated using antibody-secreting cell (ASC) assays to quantitate norovirus-specific B cells. Flow cytometry was used to analyze the phenotype of circulating B and T cells. RESULTS: The rAd-VP1 vaccine was well tolerated whereas most subjects (56%) in the controlled infection study had significant gastroenteritis 2–4 days post-inoculation. Subjects in cohorts vaccinated 28 days apart with 1 × 10(10) or 1 × 10(11) IUs showed the highest rises in serum IgG and IgA titers compared with those immunized 2 or 7 days apart with a 1 × 10(10) IU vaccine dose. Subjects in the 1 × 10(11) IU vaccine dose cohort had a 6-fold rise in serum IgA and 4-fold rise in BT50 titers, with mean IgA and IgG ASC values of 698 and 389 counts, respectively. In comparison, NoV-challenged subjects showed an average of 2,072 IgA and 886 IgG ASC counts. Remarkably, flow cytometry analysis revealed that activated B- and T-cell responses were similar post-vaccination and post-infection, with significant expansion of T follicular cells, plasmablasts, mucosal homing B cells, and preferential activation of IgA B cells. CONCLUSION: The phenotype of activated B and T cells induced post-immunization was similar to that induced post-infection, suggesting that an oral vaccine can induce comparable adaptive immune responses without the substantial adverse clinical events that occur from natural infection. Future work in dose ranging will aide in the development of a safe and efficacious oral NoV vaccine. DISCLOSURES: All Authors: No reported Disclosures.