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

• Published in: Clinical and vaccine immunology 2016-11, Vol.23 (11), p.888-900
• Main Authors: Lokhandwala, Shehnaz, Waghela, Suryakant D, Bray, Jocelyn, Martin, Cameron L, Sangewar, Neha, Charendoff, Chloe, Shetti, Rashmi, Ashley, Clay, Chen, Chang-Hsin, Berghman, Luc R, Mwangi, Duncan, Dominowski, Paul J, Foss, Dennis L, Rai, Sharath, Vora, Shaunak, Gabbert, Lindsay, Burrage, Thomas G, Brake, David, Neilan, John, Mwangi, Waithaka
• Format: Article
• Language: English
• Subjects: Adenoviridae - genetics; African Swine Fever Virus - immunology; Animals; Antigens, Viral - chemistry; Antigens, Viral - immunology; Flaviviridae; Genetic Vectors; Immunity, Cellular; Immunogenicity, Vaccine; Interferon-gamma - biosynthesis; Interferon-gamma - immunology; Swine; T-Lymphocytes, Cytotoxic - immunology; Vaccines; Vaccines, Subunit - adverse effects; Vaccines, Subunit - immunology; Viral Vaccines - adverse effects; Viral Vaccines - immunology; Virulence
• ISSN: 1556-6811; 1556-679X
• DOI: 10.1128/CVI.00395-16

The 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 (CTLs) could be the key to complete protection. Hence, generation of an efficacious subunit vaccine depends on identification of CTL targets along with a suitable delivery method that will elicit effector CTLs capable of eliminating ASFV-infected host cells and confer long-term protection. To this end, we evaluated the safety and immunogenicity of an adenovirus-vectored ASFV (Ad-ASFV) multiantigen cocktail formulated in two different adjuvants and at two immunizing doses in swine. Immunization with the cocktail rapidly induced unprecedented ASFV antigen-specific antibody and cellular immune responses against all of the antigens. The robust antibody responses underwent rapid isotype switching within 1 week postpriming, steadily increased over a 2-month period, and underwent rapid recall upon boost. Importantly, the primed antibodies strongly recognized the parental ASFV (Georgia 2007/1) by indirect fluorescence antibody (IFA) assay and Western blotting. Significant antigen-specific gamma interferon-positive (IFN-γ ) responses were detected postpriming and postboosting. Furthermore, this study is the first to demonstrate induction of ASFV antigen-specific CTL responses in commercial swine using Ad-ASFV multiantigens. The relevance of the induced immune responses in regard to protection needs to be evaluated in a challenge study.