Abstract

Novel adjuvants present a concern for adverse effects, generating a need for alternatives. Rotavirus inner capsid VP6 protein could be considered a potential candidate, due to its ability to self-assemble into highly immunogenic nanospheres and nanotubes. These nanostructures exhibit immunostimulatory properties, which resemble those of traditional adjuvants, promoting the uptake and immunogenicity of the co-administered antigens. We have previously elucidated an adjuvant effect of VP6 on co-delivered norovirus and coxsackievirus B1 virus-like particles, increasing humoral and cellular responses and sparing the dose of co-delivered antigens. This study explored an immunostimulatory effect of VP6 nanospheres on smaller antigens, P particles formed by protruding domain of a norovirus capsid protein and a short peptide, extracellular matrix protein (M2e) of influenza A virus. VP6 exhibited a notable improving impact on immune responses induced by P particles in immunized mice, including systemic and mucosal antibody and T cell responses. The adjuvant effect of VP6 nanospheres was comparable to the effect of alum, except for induction of superior mucosal and T cell responses when P particles were co-administered with VP6. However, unlike alum, VP6 did not influence M2e-specific immune responses, suggesting that the adjuvant effect of VP6 is dependent on the particulate nature of the co-administered antigen.

Highlights

  • Inner capsid VP6 protein of the triple-layered rotavirus (RV) particle exhibits polymorphic nature, being able to spontaneously assemble in vitro into trimers and further diverse and highly immunogenic nanostructures, including nanospheres and nanotubes

  • The current study reveals that VP6 potentiated antibody and T cell immune responses against P particles, but not against a M2e peptide, suggesting that VP6 nanostructures are able to promote immunogenicity of particulate antigens only

  • This study explored an adjuvant effect of VP6 nanospheres on immunogenicity of two model antigens, P particles formed by protruding domain of a norovirus capsid VP1 protein and a short peptide derived from a matrix protein M2e of influenza A virus

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Summary

Introduction

Inner capsid VP6 protein of the triple-layered rotavirus (RV) particle exhibits polymorphic nature, being able to spontaneously assemble in vitro into trimers and further diverse and highly immunogenic nanostructures, including nanospheres and nanotubes. The highly organized multivalent antigen expression, particulate nature, size and morphology [3,4,5] make these. Due to the high conservation and immunogenicity of VP6 protein, subunit vaccine candidates against RV based on VP6 have been considered a safe alternative to the current live attenuated oral RV vaccines [9,10]. We have developed a combination vaccine candidate against childhood gastroenteritis containing RV VP6 nanostructures and norovirus (NoV) virus-like particles (VLPs) [11,12], formed by self-assembly of major capsid protein VP1 [13]. Based on comprehensive preclinical studies, Vaccines 2020, 8, 365; doi:10.3390/vaccines8030365 www.mdpi.com/journal/vaccines

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