Expression Library Immunization Can Confer Protection against Lethal Challenge with African Swine Fever Virus

Abstract

African swine fever is one of the most devastating pig diseases, against which there is no vaccine available. Recent work from our laboratory has demonstrated the protective potential of DNA vaccines encoding three African swine fever viral antigens (p54, p30, and the hemagglutinin extracellular domain) fused to ubiquitin. Partial protection was afforded in the absence of detectable antibodies prior to virus challenge, and survival correlated with the presence of a large number of hemagglutinin-specific CD8 IMPORTANCEAfrican swine fever is a highly contagious disease of domestic and wild pigs that is endemic in many sub-Saharan countries, where it causes important economic losses and is currently in continuous expansion across Europe. Unfortunately, there is no treatment nor an available vaccine. Early attempts using attenuated vaccines demonstrated their potential to protect pigs against experimental infection. However, their use in the field remains controversial due to safety issues. Although inactive and subunit vaccines did not confer solid protection against experimental ASFV infection, our DNA vaccination results have generated new expectations, confirming the key role of T-cell responses in protection and the existence of multiple ASFV antigens with protective potential, more of which are currently being identified. Thus, the future might bring complex and safe formulations containing more than a single viral determinant to obtain broadly protective vaccines. We believe that obtaining the optimal vaccine formulation it is just a matter of time, investment, and willingness.

Induction of Robust Immune Responses in Swine by Using a Cocktail of Adenovirus-Vectored African Swine Fever Virus Antigens

“…Experimental subunit vaccines based on a few of these antigens have generated different protective outcomes, demonstrating that these antigens do play some role in host protection. Immunization of animals with an expression library of restriction enzyme-digested ASFV genome fragments protected 60% of the animals (42). This outcome suggests that protection through subunit vaccines is feasible but is unlikely to be highly efficacious using a single or only a few antigens.…”

Different routes and doses influence protection in pigs immunised with the naturally attenuated African swine fever virus isolate OURT88/3

“…Other studies where pigs were immunised with OURT88/3 (Oura et al., 2005) suggested that although anti-ASFV antibodies were not enough to protect pigs, their role should not be completely ruled out. As for cellular immune responses, subsets of NK cells and CD8 + T-cells have been indicated to be relevant for protection induced by some live attenuated vaccine candidates (Scholl et al., 1989, Leitão et al., 2001, Oura et al., 2005, Lacasta et al., 2015) and DNA vaccines (Argilaguet et al., 2012, Lacasta et al., 2014). More specifically, in protected pigs immunised by oronasal route with ASFV NH/P68 isolate, cytotoxic activity was mediated by CD8 + cells which lysed macrophages infected with homologous isolates under restriction of class I swine leukocyte antigen (SLA) (Martins et al., 1993).…”

Safety and immunogenicity of mammalian cell derived and Modified Vaccinia Ankara vectored African swine fever subunit antigens in swine

“…Interestingly, immune responses elicited by DNA vaccines were variable and dependent on the fusion tag (i.e., soluble HA or ubiquitin) selected for ASFV recombinant antigen expression (Argilaguet et al, 2012). A recent study using an ASFV E75 expression library containing approximately 4000 individual plasmid clones (excluding p30, p54, and CD2v) demonstrated a correlation between protection and CD8+ T-cell response (Lacasta et al, 2014). Results from this study showed that the ASFV genome (∼170-190 kb) contains additional antigens with protective potential, and implied that identification of such determinants would enable advances in the development of protective subunit vaccine candidates.…”