A Pool of Eight Virally Vectored African Swine Fever Antigens Protect Pigs against Fatal Disease

Abstract

Classical approaches to African swine fever virus (ASFV) vaccine development have not been successful; inactivated virus does not provide protection and use of live attenuated viruses generated by passage in tissue culture had a poor safety profile. Current African swine fever (ASF) vaccine research focuses on the development of modified live viruses by targeted gene deletion or subunit vaccines. The latter approach would be differentiation of vaccinated from infected animals (DIVA)-compliant, but information on which viral proteins to include in a subunit vaccine is lacking. Our previous work used DNA-prime/vaccinia-virus boost to screen 40 ASFV genes for immunogenicity, however this immunization regime did not protect animals after challenge. Here we describe the induction of both antigen and ASFV-specific antibody and cellular immune responses by different viral-vectored pools of antigens selected based on their immunogenicity in pigs. Immunization with one of these pools, comprising eight viral-vectored ASFV genes, protected 100% of pigs from fatal disease after challenge with a normally lethal dose of virulent ASFV. This data provide the basis for the further development of a subunit vaccine against this devastating disease.

Current State of Global African Swine Fever Vaccine Development under the Prevalence and Transmission of ASF in China

“…For example, some candidate strains of gene-deleted vaccines can provide complete cross-protection, and are expected to be put on the market in the near future [ 41 ]. Furthermore, significant breakthroughs have also been made in the research of virus vector vaccines, which, for the first time, achieved complete protection of vaccinated pigs against virulent strains [ 42 ].…”

“…In this study an antigen pool consisting of eight ASFV adenoviral vectors, where the ASFV genes B602L, B646L/p72, CP204L/p30, E183L/p54, E199L, EP153R, F317L, and MGF505-5R were embedded, respectively, were used to immunize pigs, and boost with MVA virus encoding the same antigen. Two animal trials were carried out successively, with promising results [ 42 ], in the second animal experiment, 6/6 of pigs were protected from lethal doses of virulent ASFV I strain. In fact, the number of survivors after vaccination with the same antigen pool differed between the two trials, presumably because the immune dose of recombinant viral vectors was increased and an overreaction of the immune system were treated with flunixin meglumine (a non-steroidal anti-inflammatory and antipyretic drug) on day 5 after challenge, compared with experiment 1, which provided 2/6 protection.…”

New Immunoinformatics Tools for Swine: Designing Epitope-Driven Vaccines, Predicting Vaccine Efficacy, and Making Vaccines on Demand

“…Thus far, little to no cross-protection has been reported ( 61 – 63 ); however, pigs that survive ASFV infection generate protection against subsequent infections with a homologous ASFV ( 58 ). Several efforts have been made to develop an ASF vaccine with a current focus on the induction of both humoral and cellular immune responses due to their potential role in conferring ASF protection ( 64 – 67 ).…”

The African Swine Fever Virus (ASFV) Topoisomerase II as a Target for Viral Prevention and Control

“…Several have already been tried and/or proposed [ 63 , 64 , 88 , 89 , 90 ], and a good option, potentially offering good safety characteristics, seems to reside on the creation of mutant viruses with self-limited replication capacity. Recent data from the use of recombinant replication-deficient adenovirus and modified vaccinia Ankara expressing ASFV proteins [ 18 ] support and encourage this approach. ASFV is expected to be extremely independent of the host cell in terms of replicative and transcriptional machineries [ 19 , 91 ], which not only implies that the ORFs coding for components of these machineries are essential but also increases the possibility for the manipulation of these aspects of the viral cycle.…”

“…In fact, a recent phase 1 clinical trial using replication-defective double deletion mutants for HSV [ 17 ] obtained promising results, suggesting that this virus may have potential to be used as a therapeutic vaccine or as a prophylactic measure. The potential of this approach for ASFV is further supported by a study published in this Special Issue reporting that domestic pigs primed by a pool of replication-deficient adenoviral vectors expressing eight ASFV genes, and boosted with modified vaccinia Ankara expressing the same genes, survived the challenge with a virulent ASFV isolate [ 18 ].…”