Inside ASFaVIP projet:
Advancing the Fight Against African Swine Fever

To date, commercially available, safe and efficacious vaccines against ASF are still lacking and production of most vaccine candidates is massively hampered by the simultaneous lack of a permanent cell line that is sufficiently susceptible to ASF virus (ASFV) and which is not forcing further genetic adaptations within the ASFV genome. The STAR-IDAZ ASFV research review (2022) further mentions, amongst others, gaps regarding viral genetic patterns associated with protection, standardization and inter-laboratory testing of vaccine candidates, and different routes of vaccination. From a safety point of view, inactivated, vector or subunit vaccines could be beneficial and are therefore targeted by several research groups. They are, however, not suitable for oral vaccination of wild boar. Inactivated preparations were tested under different conditions but were not able to confer protection from disease and death. More recently, both new adjuvants and structure-preserving inactivation procedures by gamma irradiation were revisited. In both experimental approaches, high ASFV-specific antibody titers could be induced, but a protective effect was not observed. There were even indications of an acceleration of the disease process. This is consistent with the observations of other research groups, which also turned once again to the use of inactivated preparations. Based on serological responses of recovered animals, structural proteins p30 (encoded by CP204L), p54 (E183L), p72 (B646L), pp62 (CP530R) and CD2v (EP402R) have been the main targets for rational design and were tested in protein, DNA and viral vectored ASFV vaccines in challenge studies. In addition, in silico predicted antigens expressed in a variety of vector systems have been used in different projects (e.g., the ASFORCE project). Unfortunately, results with similar antigens were not always conclusive and negative results were usually not made public. The inconsistency could be attributed to a variety of factors, including the type of vaccine, vaccination strategy, the antigens, and the immune response induced, as well as the challenge model, including factors like animal genetics, virus strain, vaccine and challenge dose, and route of challenge administration. Most approaches yielded no or very limited protection. Recently, immunogenicity and efficacy of thirty-five rationally designed adenovirus vectored ASFV antigens were evaluated in wild boar. The cocktail contained adenoviruses expressing the above-named antigens and others such as EP153R, p10, p15, CP80R, I329L, H108R, K196R, CP312R, F334L, NP419L, NP868R, B66L, H339R, and R298L, which have previously been shown to be immunogenic in domestic pigs. The rest (K145R, B385R, F165R, F778R, S273R, MGF100-1L, A224L, MGF505-6R, and B175L) were selected based on the presence of putative T cell epitopes. Also here, no protection was observed upon challenge with highly virulent ASFV. However, recently, a pool of eight ASFV antigens was shown to protect pigs from lethal disease after ASFV genotype I challenge infection when vectored by a replication-deficient human adenovirus 5 (prime) and modified vaccinia Ankara (boost). The experiments were a follow-up of previous work where different antigens were shown to be immunogenic but not protective in a DNA prime/vaccinia boost approach. The protective antigen cocktail comprised gene products of B602L, B646L (p72), CP204L (p30), E183L (p54), E199L (cysteine-rich protein), EP153R (lectin-like protein), F317L, and MGF505-5R. This approach is promising in terms of antigen choice and demonstration that a DIVA compatible subunit vaccine could confer a certain level of protection. Unfortunately, and again, no clear correlates of protection could be deduced, and all animals got sick and showed considerable viraemia. Taken together, a viral-vectored vaccine against ASF is a feasible approach, however, the choice of antigens is key to success, and convincing candidates are still missing. First live vaccine approaches existed already in the 1960s. These early live vaccines were based on attenuated strains of ASFV and were used thousands of times under field conditions in both Portugal and Spain. Unfortunately, they induced chronic lesions in many vaccinated animals (even months after vaccination) and thus even led to an increase in the number of cases in both countries. Eventually, the use of the vaccine in the field was stopped. In recent years, various promising live ASF vaccine candidates have been reported that were able to induce complete or near-complete protection against challenge infection under experimental conditions. In addition to naturally occurring variants, these are mainly genetically engineered (by homologous recombination) deletion mutants that lack, in particular, genes encoding factors that bypass the host immune system. These variants have been developed and tested by several international groups, though not homogeneous in terms of dose, route and challenge. Not all of the essentially promising results have been published to date. Promising approaches with protective efficacy against currently circulating genotype II strains of ASFV include, for example, the already mentioned U.S. vaccine candidates « ASFV-G-ΔI177L » and « ASFV-G-ΔMGF », and the Chinese vaccine candidate « HLJ/18-7GD ». The naturally evolved, non-haemadsorbing virus « Lv17/WB/Rie1 » and its derivatives have also been discussed and tested as a vaccine candidate. Other viruses with deletions in different genomic regions have been described recently and are currently under further investigation. Among these recent deletion mutants with protective efficacy is the virus « ASFV-G-ΔA137R ». Other deletion mutants showed no attenuation, e.g., the virus « ASFV-G-ΔMGF110-1L ». There are now several live vaccine candidates that could be shortlisted for a potentially licensable vaccine. However, the headlines from China, which point to chronic disease courses with more respiratory and reproductive symptoms after large-scale use of illegal live vaccine candidates, urge caution in live vaccine deployment in the field prior to sufficient clinical testing. Also, based on past experience (use of classically attenuated live vaccines in Portugal and Spain), hasty solutions in ASF vaccine development are not productive. Very recently, two live vaccines have been licensed on the Vietnamese market and are now under investigation under (more or less) controlled field conditions.