In this study, we evaluated the potential of a genetically modified
cholera toxin,
CT-E29H as an adjuvant for recombinant Norwalk virus like particle (NV-VLP)
vaccine. This detoxified mutant, containing E to H substitution at
amino acid 29 of the CT-A1 subunit, was administered with a recombinant Norwalk virus like particle
vaccine to Balb/c mice by mucosal routes to monitor the induction of mucosal, humoral and cellular responses. We observed that a low dose of NV-VLP (5 microg) with the adjuvant delivered by the intranasal route (IN) was more effective than the highest dose (200 microg) delivered by oral route at inducing both cellular and NV-VLP specific
IgG and
IgA responses. Higher counts of
antigen specific
IgA secreting cells were observed in the Peyer's Patches (PP) following delivery of the
vaccine with
CT-E29H as compared to delivery of
vaccine by mucosal routes without
CT-E29H. Furthermore, there was an increase in
antigen specific cells producing
IL-4 from animals that received the
vaccine with the adjuvant. Delivery of the
vaccine by the oral route results in
antigen specific CD4(+) and CD8(+) T cells in PP and spleen. Addition of
CT-E29H results in an increase of
antigen specific CD4(+) cell population in PP and both CD4(+) and CD8(+) populations in the spleen. These cellular and
cytokine responses suggest that combining the
vaccine with
CT-E29H results in a stronger Th2 type response. Collectively, these results indicate that immune responses to NV-VLP
vaccine are qualitatively and quantitatively improved when the
vaccine is delivered along with
CT-E29H, and thus merits its further consideration as a mucosal adjuvant.