Norovirus NoV specific protective immune responses induced by recombinant P dimer vaccine are enhanced by the mucosal adjuvant FlaBReport as inadecuate




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Journal of Translational Medicine

, 14:135

Immunobiology and immunotherapy

Abstract

BackgroundNoroviruses NoVs are a major cause of childhood gastroenteritis and foodborne diseases worldwide. Lack of appropriate animal models or cell-based culture systems makes the development and evaluation of NoV-specific vaccines a daunting task. VP1 is the major capsid protein of the NoVs that acts as a binding motif to human histo-blood group antigens HBGAs through its protruding 2 P2 domain and can serve as a protective antigen candidate for vaccine development.

MethodsRecombinantly produced NoV specific P domain Pd vaccine was inoculated into groups of mice either alone or in conjugation with mucosal adjuvant FlaB, the flagellar protein from Vibrio vulnificus. Antigen specific humoral and cell mediated immune responses were assessed by enzyme linked immunosorbent assay ELISA or fluorescent activated cell sorting FACS. A comparative analysis of various routes of vaccination viz. intranasal, sublingual and subcutaneous, was also done.

ResultsIn this study, we show that a recombinant Pd-vaccine administered through intranasal route induced a robust TH2-dependent humoral immune response and that the combination of vaccine with FlaB significantly enhanced the antibody response. Interestingly, FlaB induced a mixed TH1-TH2 type of immune response with a significant induction of IgG1 as well as IgG2a antibodies. FlaB also induced strong IgA responses in serum and feces. FlaB mediated antibody responses were toll like receptor 5 TLR5 dependent, since the FlaB adjuvanticity was lost in TLR5 mice. Further, though the Pd-vaccine by itself failed to induce a cell mediated immune response, the Pd-FlaB combination stimulated a robust CD4IFNγ and CD8IFNγ T cell response in spleen and mesenteric lymph nodes. We also compared the adjuvant effects of FlaB with that of alum and complete Freund’s adjuvant CFA. We found that subcutaneously inoculated FlaB induced more significant levels of IgG and IgA in both serum and feces compared to alum or CFA in respective samples.

ConclusionWe validate the use of TLR5 agonist as a strong mucosal adjuvant that would facilitate the development of NoV specific vaccines for humans and veterinary use. This study also highlights the importance of route of immunization in inducing the appropriate immune responses in mucosal compartments.

KeywordsNorovirus FlaB Adjuvant Antibody Intranasal Sublingual Subcutaneous Alum  Download fulltext PDF



Author: Vivek Verma - Wenzhi Tan - Sao Puth - Kyoung-Oh Cho - Shee Eun Lee - Joon Haeng Rhee

Source: https://link.springer.com/







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