Vaccination With a Gamma Irradiation-Inactivated African Swine Fever Virus Is Safe But Does Not Protect Against a Challenge

Abstract

African swine fever (ASF) is among the most devastating viral diseases of pigs and wild boar worldwide. In recent years, the disease has spread alarmingly. Despite intensive research activities, a commercialized vaccine is still not available, and efficacious live attenuated vaccine candidates raise safety concerns. From a safety perspective, inactivated preparations would be most favourable. However, both historical and more recent trials with chemical inactivation did not show an appreciable protective effect. Under the assumption that the integrity of viral particles could enhance presentation of antigens, we used gamma irradiation for inactivation. To this means, gamma irradiated ASFV “Estonia 2014” was adjuvanted with either Polygen™ or Montanide™ ISA 201 VG, respectively. Subsequently, five weaner pigs per preparation were immunized twice with a three-week interval. Six weeks after the first immunization, all animals were challenged with the highly virulent ASFV strain “Armenia 2008”. Although ASFV p72-specific IgG antibodies were detectable in all vaccinated animals prior challenge, no protection could be observed. All animals developed an acute lethal course of ASF and had to be euthanized at a moderate humane endpoint within six days. Indeed, the vaccinated pigs showed even higher clinical scores and a higher inner body temperature than the control group. However, significantly lower viral loads were detectable in spleen and liver of immunized animals at the time point of euthanasia. This phenomenon suggests an immune mediated disease enhancement that needs further investigation.

Vaccines for African swine fever: an update

“…The gamma-irradiated ASFV “Estonia 2014” has been shown to be ineffective when adjuvanted with Polygen™ or Montanide™ ISA 201 VG, respectively. Pikalo et al demonstrated that the highly virulent “Armenia 2008” ASFV strain was not protective by inoculating weaned piglets separately with the inoculated vaccine and subjecting them to the highly virulent “Armenia 2008” strain after 42 days, showing that vaccinated animals contained specific IgG but no protection ( Pikalo et al, 2022 ). Notably, animals inoculated with the ASFV-989 strain showed full clinical protection after 2 weeks of receiving the parental strain Georgia 2007/1.…”

Bridging the Gap: Can COVID-19 Research Help Combat African Swine Fever?

“…Inactivation prevents the vaccine from reverting to virulence and transmission, which can occur with some live attenuated viruses. However, despite numerous efforts, inactivated viruses have failed to elicit satisfactory protection against ASF, even with the use of advanced inactivation technologies, improved adjuvants, and high doses of inactivated viruses [ 179 , 180 , 181 ]. In many cases, the inactivated viruses were capable of inducing antibody responses in vaccinated animals.…”

Recent progress on gene-deleted live-attenuated African swine fever virus vaccines

“…A positive correlation between the antibody titers and protection outcomes has been demonstrated in pigs vaccinated with a LAV vaccine candidate and challenged with a virulent parental ASFV strain 19 . Conversely, pigs vaccinated with experimental inactivated ASF vaccines generally fail to develop protective immunity, even though they produce anti-ASFV antibodies 20 – 22 . This observation suggests that pigs infected with a live attenuated vaccine develop a different antibody profile than those vaccinated with an inactivated ASF vaccine.…”