Optimization in the expression of ASFV proteins for the development of subunit vaccines using poxviruses as delivery vectors

Jaime Lopera-Madrid,Manuel V Borca,Jorge E Osorio,Lex G Medina-Magües,Douglas P Gladue

doi:10.1038/s41598-021-02949-x

Abstract

African swine fever virus (ASFV) causes a highly contagious hemorrhagic disease that affects domestic pig and Eurasian wild boar populations. To date, no safe and efficacious treatment or vaccine against ASF is available. Nevertheless, there are several reports of protection elicited by experimental vaccines based on live attenuated ASFV and some levels of protection and reduced viremia in other approaches such as DNA, adenovirus, baculovirus, and vaccinia-based vaccines. Current ASF subunit vaccine research focuses mainly on delivering protective antigens and antigen discovery within the ASFV genome. However, due to the complex nature of ASFV, expression vectors need to be optimized to improve their immunogenicity. Therefore, in the present study, we constructed several recombinant MVA vectors to evaluate the efficiency of different promoters and secretory signal sequences in the expression and immunogenicity of the p30 protein from ASFV. Overall, the natural poxvirus PrMVA13.5L promoter induced high levels of both p30 mRNA and specific anti-p30 antibodies in mice. In contrast, the synthetic PrS5E promoter and the S E/L promoter linked to a secretory signal showed lower mRNA levels and antibodies. These findings indicate that promoter selection may be as crucial as the antigen used to develop ASFV subunit vaccines using MVA as the delivery vector.

Highlights

African swine fever virus (ASFV) causes a highly contagious hemorrhagic disease that affects domestic pig and Eurasian wild boar populations
Studies have shown that immunization of pigs with naturally attenuated ASFV strains, viruses attenuated by the passage in cell culture, or by deletions of genes involved in virus virulence can induce protection against related virulent viruses[4,5,6]
The C13L is a secretory signal from the vaccinia virus that has been used in influenza vaccine candidates that induced strong antibody titers and protection in mice[20]

Summary

Introduction

African swine fever virus (ASFV) causes a highly contagious hemorrhagic disease that affects domestic pig and Eurasian wild boar populations. In the present study, we constructed several recombinant MVA vectors to evaluate the efficiency of different promoters and secretory signal sequences in the expression and immunogenicity of the p30 protein from ASFV. The synthetic PrS5E promoter and the S E/L promoter linked to a secretory signal showed lower mRNA levels and antibodies These findings indicate that promoter selection may be as crucial as the antigen used to develop ASFV subunit vaccines using MVA as the delivery vector. The growth in information regarding ASFV genes’ functions and available genomic sequences from isolates has opened the possibility for the rational design of ASF vaccines In this regard, some progress has been made in identifying proteins that may induce a protective response. In the case of ASFV, recent studies have demonstrated the immunogenicity of MVA when used as a viral vector to express ASFV antigens in pigs[15,16]

Methods

Results

Conclusion