DNA-Protein Vaccination Strategy Does Not Protect from Challenge with African Swine Fever Virus Armenia 2007 Strain.

Sun-Young Sunwoo,Yolanda Revilla,In Kim,Marisa Nogal,Jessie Trujillo,Elena Sánchez,Wenjun Ma,Daniel Pérez-Núñez,Natasha Gaudreault,Lina Mur,Kinga Urbaniak,Juergen Richt,Igor Morozov,Daniel Madden

doi:10.3390/vaccines7010012

Abstract

African swine fever virus (ASFV) causes high morbidity and mortality in swine (Sus scrofa), for which there is no commercially available vaccine. Recent outbreaks of the virus in Trans-Caucasus countries, Eastern Europe, Belgium and China highlight the urgent need to develop effective vaccines against ASFV. Previously, we evaluated the immunogenicity of a vaccination strategy designed to test various combinations of ASFV antigens encoded by DNA plasmids and recombinant proteins with the aim to activate both humoral and cellular immunity. Based on our previous results, the objective of this study was to test the combined DNA-protein vaccine strategy using a cocktail of the most immunogenic antigens against virulent ASFV challenge. Pigs were vaccinated three times with a cocktail that included ASFV plasmid DNA (CD2v, p72, p32, +/−p17) and recombinant proteins (p15, p35, p54, +/−p17). Three weeks after the third immunization, all pigs were challenged with the virulent ASFV Armenia 2007 strain. The results showed that vaccinated pigs were not protected from ASFV infection or disease. Compared to the non-vaccinated controls, earlier onset of clinical signs, viremia, and death were observed for the vaccinated animals following virulent ASFV challenge. ASFV induced pathology was also enhanced in the vaccinated pigs. Furthermore, while the vaccinated pigs developed antigen-specific antibodies, immunized pig sera at the time of challenge lacked the capacity to neutralize virus, and instead was observed to enhance ASFV infection in vitro. The results of this work points to a putative immune enhancement mechanism involved in ASFV pathogenesis that warrants further investigation. This pilot study provides insight for the selection of appropriate combinations of ASFV antigens for the development of a rationally-designed, safe, and efficacious vaccine for ASF.

Highlights

African swine fever (ASF), is caused by a large enveloped DNA virus (ASFV) of the familyAsfarviridae [1,2]
Sera from pigs immunized three times and non-vaccinated controls were tested by Enzyme-linked immunosorbent assays (ELISAs) against individual p15, p35, p54, and p17 recombinant proteins
The results showed similar antibody responses in both groups of immunized pigs against African swine fever virus (ASFV) proteins p15, p35, and p54 at 49 days post initial vaccination (Figure 1)

Summary

Introduction

African swine fever (ASF), is caused by a large enveloped DNA virus (ASFV) of the familyAsfarviridae [1,2]. African swine fever (ASF), is caused by a large enveloped DNA virus (ASFV) of the family. Virulent ASFV strains cause acute hemorrhagic fever in domestic pigs and wild boar (Sus scrofa) with up to 100% mortality within 12 days after infection, while other ASFV strains cause subacute or mild disease [3]. ASF is considered one of the most significant and devastating viral diseases of domestic pigs primarily due to the lack of effective vaccines [4]. The development of an effective, safe ASFV vaccine has been largely unsuccessful due to the complexity of the virus. ASFV encodes for more than 150 viral proteins, making the identification of individual, or combinations of, viral antigens that may elicit a protective response against ASF challenging [7].

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