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

Abstract

eThe African swine fever virus (ASFV) causes a fatal hemorrhagic disease in domestic swine, and at present no treatment or vaccine is available. Natural and gene-deleted, live attenuated strains protect against closely related virulent strains; however, they are yet to be deployed and evaluated in the field to rule out chronic persistence and a potential for reversion to virulence. Previous studies suggest that antibodies play a role in protection, but induction of cytotoxic T lymphocytes (

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

“…The identified adhesion probability scores for EP402R (CD2v) (score 0.457) and EP153R (score 0.372) correlate with previous reports that have shown that these proteins are involved in ASFV hemadsorption (HA) in vitro (Borca et al, 1998(Borca et al, , 1994bGalindo et al, 2000;Neilan et al, 1999;Rodríguez et al, 1993;Ruiz-Gonzalvo et al, 1996). Adhesion probability scores were identified for B646L/p72 (score 0.25), CP204L/p30 (score 0.363), and E183L/p54 (score 0.566), all previously reported to be potential protective antigens (Argilaguet et al, 2012;Gómez-Puertas et al, 1998;Lokhandwala et al, 2016;Neilan et al, 2004). A 20% weight for each MHC class epitopes was chosen to select both classes of epitopes equally to maximize immunogenicity potential.…”

“…In contrast, pigs that were administered MVA-ASFV construct cocktails failed to generate detectable ASFV antibody responses. This outcome was somewhat unexpected since this expression system elicited antibodies when used with other antigens (Brewoo et al, 2010) and another viral-vector system (human adenovirus 5) elicited antibodies when used with some of the same (E183L, B646L) antigens (Lokhandwala et al, 2016). The lack of antibody response may be related to a defect in antigen presentation, e.g., the retention of the MVA expressed ASFV antigens inside infected cells may have limited their presentation to B-cells (Borrego et al, 2006;Ganges et al, 2005).…”

“…These results are in congruence with previous reports that emphasize the importance of heterologous prime/boost regimes (Boyd et al, 2013;Draper et al, 2013;Pattacini et al, 2012;Ratto-Kim et al, 2012) and correlate with recent relevant reports. Interestingly, antigen-specific IFN-␥ + T-cell responses to B646L were also observed following an adenoviral-vector homologous prime/boost immunization strategy (Lokhandwala et al, 2016). However it should be noted that the correlation between IFN-␥ + T-cell responses and host protection against ASFV remains unclear, at least in the context of using live, attenuated ASFV models (Carlson et al, 2016).…”

“…Recently, an adenovirus-vectored ASFV multiantigen cocktail expressing p32 (CP204L), p54 (E183L), pp62 (polyprotein) and p72 (B646L) antigens was demonstrated to induce antigen-specific antibodies and T-cell responses in the absence of ASFV challenge (Lokhandwala et al, 2016). The antibody and T-cell activity reported with this adenovirus-vectored ASFV multiantigen cocktail appears to be more robust and broader compared to the MVA-ASFV prime/HEK-ASF antigen boost strategy used in the present study.…”

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

“…A large number of studies have demonstrated that virus vectored vaccine can induce strong specific antibody-mediated humoral responses and IFN-γ secreting cellular responses in pigs, which can provide partial effective protection against ASFV challenge [ 96 , 97 , 98 ]. In 2019, as shown in Table 4 , Lokhandwala’s group evaluated the immune response and protective effect induced by two recombinant adenovirus combinations, Ad-ASFV-I (A151R, B119L, B602L, EP402R∆PRR, B438L, K205R, A104R, pp62, and p72) and Ad-ASFV-II (p30, p54, pp62, p72, and pp220), by intranasal challenge of ASFV-Georgia 2007/1 on the basis of previous studies.…”