Key result
Sequential intramuscular and intranasal immunization with a Norovirus VLP vaccine in mice induced broad immune responses, compensating for deficient IgA and CD8+ T cell responses seen with either route alone.
Sequential intramuscular and intranasal administration of a Norovirus VLP vaccine candidate in mice induces broader systemic and mucosal immune responses than either route alone.
Hypothesis-generating for dual-route norovirus vaccines in models; leaves clinical translation and human efficacy open.
Background and objectives: Noroviruses (NoVs) are major causative agents of non-bacterial acute gastroenteritis in people of all ages worldwide.NoV capsid VP1 derived virus-like particles (VLPs) produced in various expression systems are main vaccine candidates against NoV.The aim of this study was to investigate and compare systemic and mucosal delivery and a combination of both deliveries of NoV VLPs for induction of immune responses in BALB/c mice.Materials and methods: BALB/c mice were immunized Intramuscularly (IM), Intranasally (IN) or sequentially (IM followed by IN) with a candidate NoV GII-4 VLP vaccine developed by our laboratory.NoV GII-4-specific serum and mucosal IgG and IgA antibodies were analyzed by ELISA.GII-4-specific T cell immune responses were investigated using an ELISPOT assay measuring production of interferon-γ (IFN-γ) at a single cell level.Results: IM immunized mice developed a strong systemic and mucosal NoV-specific IgG antibody response but completely lacked IgA response.In contrast, mice immunized IN had strong systemic and mucosal IgG and IgA production but lacked CD8 + T cell responses.Sequential immunization compensated for the deficient IgA and CD8 + T cell responses induced by each delivery alone. Conclusion:Our results show that sequential IM+IN immunization should be considered for NoV VLP vaccine delivery to activate broad immune responses.
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Maria Malm Kirsi Tamminen (2015) studied Norovirus infection. Norovirus GII-4 VLP vaccine (sequential IM+IN) vs. IM alone or IN alone was evaluated on NoV GII-4-specific serum and mucosal IgG and IgA antibodies and T cell immune responses. Sequential intramuscular and intranasal immunization with a Norovirus VLP vaccine in mice induced broad immune responses, compensating for deficient IgA and CD8+ T cell responses seen with either route alone.
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