Location: Foreign Animal Disease Research
Project Number: 3022-32000-063-027-S
Project Type: Non-Assistance Cooperative Agreement
Start Date: Jun 1, 2021
End Date: May 31, 2024
Objective:
African swine fever (ASF) is currently causing outbreaks from Central Europe to south east Asia, causing devastating losses to the swine industry. Currently, there only experimental live-attenuated vaccines showing a protective effect against this highly virulent outbreak strain. The use of live attenuated vaccines (LAV) have their limitations, particularly free-disease areas. In addition, Classical Swine Fever (CSF) is endemic in the Caribbean and Central America and remained endemic in China, the biggest pig producer worldwide despite the wide use of CSF vaccination programs. The objective of this proposal is to develop a novel experimental subunit vaccines to ASF, CSF and ASF/CSF based in the use of self-amplifying (sa) mRNA-nanoparticles (NP). This project will also give the opportunity to test the immunogenicity of ASFV proteins previously identified by ARS scientists as specifically recognized during the protective antibody response elicited in in animals efficaciously vaccinated with LAVs.
Approach:
ASFV and CSFV proteins identified as critical in the induction of a protective immune response in pigs will be tested as experimental subunit vaccines using the self-amplifying (sa) mRNA inorganic nanoparticle technology. Self-amplifying mRNA is derived from the non-structural genes of TC-83 alphavirus and requires only 1-2 ug of sa mRNA when combined with nanoparticle technology to produce immunity in swine. The nanoparticle has an outer cationic charge that allows for simplicity in manufacture in that the sa mRNA is stabilized by its attachment to the surface of the nanoparticle. The resultant sa mRNA-nanoparticle vaccine is stable at refrigerator temperatures. The sa mRNA-nanopore technology is unique in that less sa mRNA is required than with non-self-amplifying mRNA vaccines. Genvax ‘s technology for self-amplifying (sa) mRNA nanoparticle technology is the same concept used in in the development of a vaccine for Covid 19. Genvax has conducted proof of concept studies in pigs with a sa mRNA-lipid inorganic nano particle vaccine containing the hemagglutinin gene of swine influenza virus and shown robust immune response and protection against viral challenge.
The sa mRNA-nanoparticle vaccine platform will contain transgene sequences that express 20 viral proteins for ASFV, CSFV or a combination of ASFV and CSFV proteins. The vaccine platform will be tested in its efficacy in inducing cellular and antibody response to its components and protection again the challenge with the corresponding virulent virus.
