African swine fever control and prevention: an update on vaccine development

Abstract

African swine fever (ASF) is a lethal and highly contagious viral disease of domestic and wild pigs, listed as a notifiable disease reported to the World Organization for Animal Health (OIE). Despite its limited host range and absent zoonotic potential, the socio-economic and environmental impact of ASF is very high, representing a serious threat to the global swine industry and the many stakeholders involved. Currently, only control and eradication measures based mainly on early detection and strict stamping-out policies are available, however, the rapid spread of the disease in new countries, and in new regions in countries already affected, show these strategies to be lacking. In this review, we discuss approaches to ASF vaccinology, with emphasis on the advances made over the last decade, including the development of virulence-associated gene deleted strains such as the very promising ASFV-G-ΔI177L/ΔLVR, that replicates efficiently in a stable porcine epithelial cell line, and the cross-protecting BA71ΔCD2 capable of stably growing in the commercial COS-1 cell line, or the naturally attenuated Lv17/WB/Rie1 which shows solid protection in wild boar. We also consider the key constraints involved in the scale-up and commercialization of promising live attenuated and virus-vectored vaccine candidates, namely cross-protection, safety, lack of suitable animal models, compatibility with wildlife immunization, availability of established and licensed cell lines, and differentiating infected from vaccinated animals (DIVA) strategy.

Keywords: African swine fever; control; domestic pigs; immune response; live attenuated; review; vaccine; wild boar.

Graphical abstract

Figure 1.

Immune responses to ASFV infection. Both humoral and cellular immune responses appear to be important for protection against ASFV infection. T cells have been shown to play a particularly important role in survival with key roles identified for natural killer (NK) and CD8+ T cells. CD4+ T helper cells seem to support B cell responses and essential antibody (Ab) maturation, particularly in infection with highly virulent isolates. Studies on nonconventional T cells, such as effector γδ T cells and invariant Natural Killer T (iNKT) cells, indicate these cell subsets also take part in the antiviral response against ASFV. In wild boar, the significant bias towards γδ T cells has been suggested as an explanation for the higher disease severity and lethality in this species. Several studies have also revealed the relevance of antibodies in the protection against ASF. Antibody-mediated neutralization has some uncommon characteristics in ASFV infection, namely loss of susceptibility to neutralization by cell culture passage because of changes in the phospholipid composition of viral membranes and/or the presence of sera blocking antibodies that inhibit complete neutralization. A number of ASFV proteins have been implicated in the induction of neutralizing antibodies during infection, most notably the ASFV hemagglutinin CD2v/EP402R. Other antibody driven protective mechanisms include antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-mediated cytotoxicity (CDC). Created with BioRender.com (accessed on 01 July 2022).

Figure 2.

Different approaches for the development of vaccine candidates against ASFV. Three main strategies have been employed in the development of ASFV vaccine candidates: whole inactivated ASF virus vaccines; live virus-vectored recombinant, subunit, and mammalian expression plasmid vaccines; and live attenuated virus vaccines (LAVs), which we have further subcategorized into naturally attenuated or attenuated by cell passage, and gene deleted vaccines. The figure highlights the main advantages and disadvantages of each approach, as well as existing examples under development. DIVA – Differentiating Infected from Vaccinated Animals. Created with BioRender.com (accessed on 01 July 2022).