Abstract
ABSTRACTAfrican swine fever virus (ASFV) causes an acute hemorrhagic fever in domestic pigs, with high socioeconomic impact. No vaccine is available, limiting options for control. Although live attenuated ASFV can induce up to 100% protection against lethal challenge, little is known of the antigens which induce this protective response. To identify additional ASFV immunogenic and potentially protective antigens, we cloned 47 viral genes in individual plasmids for gene vaccination and in recombinant vaccinia viruses. These antigens were selected to include proteins with different functions and timing of expression. Pools of up to 22 antigens were delivered by DNA prime and recombinant vaccinia virus boost to groups of pigs. Responses of immune lymphocytes from pigs to individual recombinant proteins and to ASFV were measured by interferon gamma enzyme-linked immunosorbent spot (ELISpot) assays to identify a subset of the antigens that consistently induced the highest responses. All 47 antigens were then delivered to pigs by DNA prime and recombinant vaccinia virus boost, and pigs were challenged with a lethal dose of ASFV isolate Georgia 2007/1. Although pigs developed clinical and pathological signs consistent with acute ASFV, viral genome levels were significantly reduced in blood and several lymph tissues in those pigs immunized with vectors expressing ASFV antigens compared with the levels in control pigs.IMPORTANCE The lack of a vaccine limits the options to control African swine fever. Advances have been made in the development of genetically modified live attenuated ASFV that can induce protection against challenge. However, there may be safety issues relating to the use of these in the field. There is little information about ASFV antigens that can induce a protective immune response against challenge. We carried out a large screen of 30% of ASFV antigens by delivering individual genes in different pools to pigs by DNA immunization prime and recombinant vaccinia virus boost. The responses in immunized pigs to these individual antigens were compared to identify the most immunogenic. Lethal challenge of pigs immunized with a pool of antigens resulted in reduced levels of virus in blood and lymph tissues compared to those in pigs immunized with control vectors. Novel immunogenic ASFV proteins have been identified for further testing as vaccine candidates.
Highlights
IMPORTANCE The lack of a vaccine limits the options to control African swine fever
The depletion studies did not provide information on which CD8ϩ cell subset was important for protection, additional studies have shown a correlation between induction of the CD4ϩ CD8ϩ, perforinϩ cytotoxic T lymphocytes (CTL) with protection induced by the attenuated OURT88/3 strain [6]
The larger proteins were cloned in several fragments to facilitate their expression. This approach was taken to represent the diversity of antigens expressed during an African swine fever virus (ASFV) infection. These 47 genes or gene fragments were cloned in vectors for gene immunization, for expression in recombinant vaccinia virus vectors, and for recombinant protein expression by in vitro transcription and translation
Summary
IMPORTANCE The lack of a vaccine limits the options to control African swine fever. Advances have been made in the development of genetically modified live attenuated ASFV that can induce protection against challenge. There is little information about ASFV antigens that can induce a protective immune response against challenge. Immunization of pigs with attenuated strain OURT88/3 induces protection against lethal challenge that is dependent on CD8ϩ cells, since protection was abrogated by depletion of this cell subset [5]. The depletion studies did not provide information on which CD8ϩ cell subset was important for protection, additional studies have shown a correlation between induction of the CD4ϩ CD8ϩ, perforinϩ cytotoxic T lymphocytes (CTL) with protection induced by the attenuated OURT88/3 strain [6]. Live attenuated ASFV strains can induce protection of up to 100%, they can cause adverse reactions and may have other safety issues. Attempts to induce protection against lethal ASFV challenge by immunization of pigs with recombinant proteins or by DNA vaccination have had partial success. Other ASFV proteins are likely to have the potential to be protective but have not been systematically investigated
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