Intranasal vaccination with an adjuvanted Norwalk virus-like particle vaccine elicits antigen-specific B memory responses in human adult volunteers

Noroviruses are the most frequent cause of acute gastroenteritis in humans of all ages. No vaccines are currently available. An intranasally delivered Norwalk (NV) virus-like particle (VLP) vaccine was recently shown to be well tolerated, immunogenic and to protect against infection in Phase 1 studies. Here, we examined B memory (BM) responses in volunteers who received the highest dosage levels of the NV-VLP vaccine (50 μg and 100 μg). We measured the frequency of NV-specific IgG and IgA-secreting BM cells in peripheral blood and the level of antibodies produced by these cells in culture. All subjects immunized with 100 μg of the NV-VLP vaccine and 90% of those who received 50 μg had significant IgA or IgG BM responses. The BM cell frequencies correlated with serum antibody levels and mucosally-primed antibody-secreting cell responses. This is the first demonstration of dose-dependent, functional BM responses in humans immunized intranasally with a NV-VLP vaccine.

► We studied B memory cells in humans immunized with Norwalk virus-like particles. ► BM cell frequency was measured in blood from volunteers immunized intranasally. ► All subjects that received 100 μg of VLP developed IgG and IgA-secreting BM cells. ► BM cell responses correlated with serum antibodies and antibody secreting cells. ► This is the first report of human BM responses to an intranasal Norwalk VLP vaccine.