Abstract
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.
Highlights
Noroviruses (NoV) are the leading cause of non-bacterial acute gastroenteritis (AGE) in people of all ages
Our results show that sequential IM+IN immunization should be considered for NoV virus-like particles (VLPs) vaccine delivery to activate broad immune responses
To analyze NoV GII-4 VLP induced immune responses 10 female BALB/c OlaHsd mice (7 weeks old; Harlan Laboratories, The Netherlands) were immunized at day 0 and day 21 with a NoV VLP and rotavirus VP6 combination vaccine candidate developed by our laboratory [12,23] containing 10 μg GII-4 VLPs by IM or IN route
Summary
Noroviruses (NoV) are the leading cause of non-bacterial acute gastroenteritis (AGE) in people of all ages. After introduction of rotavirus vaccines in the USA, Finland, and other countries, NoVs have become the leading cause of medically attended AGE in children under five years of age [2,3]. After expression in vitro major NoV capsid protein selfassembles into virus-like particles (VLPs) consisting of 90 dimers of VP1 [6]. These VLPs are morphologically and functionally similar to the native virus but lack genetic material. Noroviruses (NoVs) are major causative agents of non-bacterial acute gastroenteritis in people of all ages worldwide. 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
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