A Novel Live Attenuated Vaccine Candidate Protects Against Heterologous Senecavirus A Challenge

Abstract

Senecavirus A (SVA) is an emerging picornavirus causing vesicular disease (VD) clinically indistinguishable from foot-and-mouth disease (FMD) in pigs. Currently there are no vaccines currently available for SVA. Here we developed a recombinant SVA strain (rSVAm SacII) using reverse genetics and assessed its immunogenicity and protective efficacy in pigs. In vivo characterization of the rSVAm SacII strain demonstrated that the virus is attenuated, as evidenced by absence of lesions, decreased viremia and virus shedding in inoculated animals. Notably, while attenuated, rSVA mSacII virus retained its immunogenicity as high neutralizing antibody (NA) responses were detected in inoculated animals. To assess the immunogenicity and protective efficacy of rSVA mSacII, 4-week-old piglets were sham-immunized or immunized with inactivated or live rSVA mSacII virus-based formulations. A single immunization with live rSVA mSacII virus via the intramuscular (IM) and intranasal (IN) routes resulted in robust NA responses with antibodies being detected between days 3–7 pi. Neutralizing antibody responses in animals immunized with the inactivated virus via the IM route were delayed and only detected after a booster on day 21 pi. Immunization with live virus resulted in recall T cell proliferation (CD4+, CD8+, and CD4+/CD8+ T cells), demonstrating efficient stimulation of cellular immunity. Notably, a single dose of the live attenuated vaccine candidate resulted in protection against heterologous SVA challenge, as demonstrated by absence of overt disease and reduced viremia, virus shedding and viral load in tissues. The live attenuated vaccine candidate developed here represents a promising alternative to prevent and control SVA in swine.

Preliminary Evaluation of Protective Efficacy of Inactivated Senecavirus A on Pigs

“…Thus, we think that the development of SVA vaccine is meaningful and can curb the prevalence of SVA. However, there were few reports about the research of SVA vaccine [ 17 , 20 , 21 ] and no commercial vaccine for SVA was available. Thus, it was necessary to continue the research of SVA vaccine.…”

A virulent and pathogenic infectious clone of Senecavirus A

“…of 10, and harvested at 4, 8, 12 and 24 h p.i. SDS-PAGE and Western blot were performed as previously described [25]. Nitrocellulose membranes were incubated with anti-VP1, anti-VP2 (kindly provided by Drs.…”

“…The development of reverse genetic systems for RNA viruses has provided critical platforms to study the effects of targeted genetic changes on virus replication and pathogenesis [24]. Currently, few infectious clones of SVA have been developed [25–29], however they demonstrated to be attenuated in pigs [25, 26].…”

A 5-Year Review of Senecavirus A in China since Its Emergence in 2015

“…Moreover, the SVA can efficiently propagate in BHK-21 cells to reach a high titer, even more than 10 9 TCID 50 /mL in culture supernatant, greatly facilitating mass production of seed stocks. Sharma et al ( 67 ) developed a novel candidate of live-attenuated vaccine, with which a single immunization could confer protection against heterologous SVA challenge, as demonstrated by absence of overt disease and reduced viremia, virus shedding and viral load in tissues ( 67 ). This candidate represents a promising alternative to prevent SVA infection in pigs.…”