Attenuated african swine fever virus strain induces protection against challenge with homologous virulent parental virus georgia 2007 isolate

Inventors

Borca, Manuel V. • Holinka-Patterson, Lauren G. • Gladue, Douglas • Risatti, Guillermo R. • O'Donnell, Vivian K.

Assignees

University of Connecticut • US Department of Agriculture USDA

Abstract

African swine fever virus (ASFV) is the etiological agent of a contagious and often lethal viral disease of domestic pigs that has significant economic consequences for swine breeding. Control of ASF has been hampered by the unavailability of vaccines. Recombinant viruses harboring engineered deletions of specific virulence-associated genes induce solid protection against the challenge with parental viruses. Here we report the construction of a recombinant Δ9GL virus derived from the highly virulent ASFV Georgia 2007 (ASFV-G) isolate. In vivo, ASFV-G Δ9GL administered intramuscularly (IM) to swine at relatively high doses (104 HAD50) retains a virulent phenotype practically indistinguishable from the parental virus. Conversely, at low IM doses (102 or 103 HAD50), ASFV-G Δ9GL does not induce disease. Importantly, animals infected with 103 HAD50 are protected against the presentation of clinical disease when challenge at 28 days post infection with the virulent parental strain Georgia 2007.

Core Innovation

African Swine Fever Virus (ASFV) causes a contagious and often lethal disease in domestic pigs, severely impacting swine breeding economics. Control efforts have been hindered by the absence of vaccines. Prior attempts, including using infected cell extracts and inactivated virions, failed to induce protective immunity. However, recombinant viruses with engineered deletions of virulence-associated genes, such as the 9GL gene, have shown solid protection against homologous parental virus challenges in some ASFV isolates.

This invention reports the construction of a recombinant Δ9GL virus derived from the highly virulent ASFV Georgia 2007 (ASFV-G) isolate by deleting a significant portion of the 9GL gene. While high doses of this mutant virus retain a virulent phenotype similar to the parental virus, low doses do not induce disease and provide protection against subsequent challenge with the virulent parental strain. The invention also entails immunogenic compositions comprising this viable mutant virus, constituting a rationally designed live attenuated vaccine effective against clinical ASF in swine.

Further, the invention provides a method for protecting animals by administering an effective amount of the ASFV-G Δ9GL vaccine and introduces a genetic marker approach to differentiate vaccinated animals from those infected with wild-type ASFV-G. The mutant 9GL polypeptide expressed by the recombinant virus is shorter due to deletion of amino acids 11 through 68, enabling genetic distinction. The vaccine can be administered intramuscularly, subcutaneously, or intranasally, and dosage optimization is described to achieve immunity without inducing severe disease.

Claims Coverage

The claims present three main inventive features centered on a recombinant ASFV-G mutant, its application in vaccines, and methods for protecting swine.

Together, the claims define a live attenuated ASFV vaccine based on a recombinant virus with a targeted 9GL gene deletion, formulations of this vaccine, and methods of use for protecting swine against ASFV-G infection.

Stated Advantages

Documented Applications