Immunogenicity and Efficacy Evaluation of Subunit Astrovirus Vaccines

TY - JOUR

T1 - Immunogenicity and Efficacy Evaluation of Subunit Astrovirus Vaccines

AU - Bidokhti, Mehdi R.m.

AU - Ullman, Karin

AU - Hammer, Anne Sofie

AU - Jensen, Trine Hammer

AU - Chriél, Mariann

AU - Byrareddy, Siddappa N.

AU - Baule, Claudia

PY - 2019/9

Y1 - 2019/9

N2 - 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 CP∆N (spanning amino acids 161–775) and CP∆C (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 CP∆N. 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 CP∆N. 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.

AB - 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 CP∆N (spanning amino acids 161–775) and CP∆C (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 CP∆N. 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 CP∆N. 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.

U2 - 10.3390/vaccines7030079

DO - 10.3390/vaccines7030079

M3 - Journal article

C2 - 31382451

SN - 2076-393X

VL - 7

JO - Vaccines

JF - Vaccines

IS - 3

M1 - 79

ER -