Immunogenicity and Efficacy Evaluation of Subunit Astrovirus Vaccines

Mehdi R.M Bidokhti,Claudia Baule,Anne Sofie Hammer,Siddappa N Byrareddy,Karin Ullman,Mariann Chriél,Trine Hammer Jensen

doi:10.3390/vaccines7030079

Abstract

A full understanding of the immune response to astrovirus (AstV) infection is required to treat and control AstV-induced gastroenteritis. Relative contributions of each arm of the immune system in restricting AstV infection remain unknown. In this study, two novel subunit AstV vaccines derived from capsid protein (CP) of mink AstV (MAstV) such as CPΔN (spanning amino acids 161–775) and CPΔC (spanning amino acids 1–621) were evaluated. Their immunogenicity and cytokine production in mice, as well as protective efficacy in mink litters via maternal immunization, were studied. Truncated CPs induced higher levels of serum anti-CP antibodies than CP, with the highest level for CPΔN. No seronegativity was detected after booster immunization with either AstV CP truncates in both mice and mink. All mink moms stayed seropositive during the entire 104-day study. Furthermore, lymphoproliferation responses and Th1/Th2 cytokine induction of mice splenocytes ex vivo re-stimulated by truncated CPs were significantly higher than those by CP, with the highest level for CPΔN. Immunization of mink moms with truncated CPs could suppress virus shedding and clinical signs in their litters during a 51-day study after challenge with a heterogeneous MAstV strain. Collectively, AstV truncated CPs exhibit better parameters for protection than full-length CP.

Highlights

Immunization against the viral pathogens causing gastrointestinal disorders is one of the most important concerns in public and animal health
Blood of mice immunized with capsid protein (CP), CP∆N, or second
Our findings show that truncation disrupts this antiviral suppression activity of AstV CP, leading to better crosstalk between humoral and cellular immune responses

Summary

Introduction

Immunization against the viral pathogens causing gastrointestinal disorders is one of the most important concerns in public and animal health. Development of viral vaccines has traditionally been based on the use of attenuated live or inactivated viruses to induce protective immunity. This strategy has generated both live attenuated and inactivated vaccines currently in use for different diseases. Inactivated vaccines, on the other hand, are safe but poorly immunogenic [1,2]. Subunit vaccines target specific epitopes recognized for immunity and are safe since they do not involve replication of the viral pathogen. These need to be combined with adjuvants to stimulate good immune responses and often require repeated immunization. Vital aspects for subunit vaccines effectivity are that the right

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