doi: 10.15389/agrobiology.2017.6.1069eng

UDC 636.4:619:616.636:578:[577.2.08+51-76

 

MECHANISMS OF IMMUNE RESPONSE AND PROSPECTS FOR
DNA VACCINES AGAINST AFRICAN SWINE FEVER (review)

A.D. Sereda, A.R. Imatdinov, O.A. Dubrovskaya, D.V. Kolbasov

Federal Research Center for Virology and Microbiology, Federal Agency of Scientific Organizations, 1, ul. Akademika Bakuleva, pos. Vol’ginskii, Petushinskii Region, Vladimir Province, 601125 Russia, e-mail sereda-56@mail.ru

ORCID:
Sereda A.D. orcid.org/0000-0001-8300-5234
Imatdinov A.R. orcid.org/0000-0003-2889-6112
Kolbasov D.V. orcid.org/0000-0002-4935-0891
Dubrovskaya O.A. orcid.org/0000-0002-3168-7947

Received May 4, 2017

 

The agent of African swine fever (ASF) is a large envelope virus (ASFV) belonging to family Asfarviridae and containing a double-stranded linear DNA of 170 to 190 kb in size coding for more than 150 proteins, most of which are involved in host-virus interactions (L.K. Dixon et al., 2004). Its virulent isolates cause a contagious hemorrhagic disease with 100 % mortality both among domestic pigs (Sus scrofa domesticus) and wild boars (Sus scrofa). The disease control is complicated by the lack of any specific preventive methods (R.J. Rowlands et al., 2008; D.A. Chapman et al., 2011; P. Rahimi et al., 2010). The attempts to protect pigs against ASF with experimental live and inactivated subunit vaccines developed by standard methods failed (S. Blome et al., 2014). This paper discusses immunological mechanisms to provide the specific defense base on potentially protective virus-specific proteins, and immunogenic and some protective properties of ASFV gene-based DNA constructs. Immune protection at ASF is due to cytotoxic T-lymphocytes (CTL) and antibody-dependent cell-mediated cytotoxicity (ADCC) effectors against viral proteins located on infected monocyte/mac-rophage. There is a synergism of these effectors (A.D. Sereda, 2013). Based on i) the location, structure and functional properties of viral proteins, ii) the polypeptide specificity of blood antibodies after injecting pigs with ASFV attenuated or virulent strains, iii) the effects of pig immunization using purified proteins from infected cells or the recombinant proteins, and DNN constructs, p30, p54 and CD2v proteins are considered as potentially protective (S.D. Kollnberger et al., 2002; M.G. Barderas et al., 2001; J.G. Neilan et al., 2004). A significant disadvantage of the candidate DNA vaccine is a relatively low immune response, especially in large mammals. There were attempts of overcoming the problem using various strategies (J. Rajcani et al., 2005, M.A. Liu et al., 2006; L.H. van Drunen et al., 2004; J.A. Leifert et al., 2004). To target the lymphocytes expressing receptors CD48 and CD58 to the protein CD2 of the antigen presenting cells (APC), the secretory part (s) of ASFV protein HA (or CD2v) has been used (A. Brossay et al., 2003; K. Crosby et al., 2004). The addition of sHA gene to the DNA construct enhanced both humoral and cellular responses in pigs against fused recombinant proteins p30 and p54 (F. Ruiz-Gonzalvo et al., 1996). An increase in the humoral response due to targeting p30 and p54 fused to one chain of the antibody recognizing the invariant epitope of pig class II main histocompatibility complex (MHC) was demonstrated. However, the enhancement of the humoral immune response to p30 and p54 rather often resulted in earlier death of pigs infected with virulent strains. To stimulate the specific CD8+-T-cell responses, a pCMV-UbsHAPQ construct coding for antigenic determinants p30, p54 and sHA fused with cellular ubiquitin (Ub) was developed. The immunization using pCMV-UbsHAPQ did not induce an instrumentally determined antibody response though provided partially pig protection against ASFV challenge (J.M. Argilaguet et al., 2011). The potential of the DNA constructs was confirmed by pig immunization using ASFV DNA libraries (ASFVUblib) coding for viral genome short fragments combined with the cellular ubiquitin gene (A. Lacasta et al., 2014). In the 4029 clones, about 76 % of the viral genome (130 kb) were covered. As many as 60 % of ASFVUblib-immunized pigs survived after infection with an ASFV virulent strain. According to ELISA, none of the ASFVUblib-immunized pig had detectable specific antibodies to ASFV proteins prior to the challenge. The CD8+-T-cells comprised the only cell sub-population among the studied ones that showed a statistically significant growth in the survived pigs starting from day 5 post immunization. The opportunities for a vaccination strategy based on the use of BacMam viruses that are baculovirus vectors encoding viral antigens under the control of cell-active promoters of vertebrates have been analyzed (J.M. Argilaguet et al., 2013). Immunization with recombinant baculovirus (BacMam-sHAPQ) encoding two ASFV full-length immunodominant proteins p30 and p54 fused to a carboxyl terminus of the extracellular domain of a viral hemagglutinin sHA resulted in no viraemia or clinical signs of the disease in 66 % of the pigs. Moreover, BacMam-sHAPQ-immunized animal had no ELISA-detectable virus-specific antibody prior to challenge. Thus, the prospect for development of DNA vaccine against ASFV seems to be encouraging.

Keywords: DNA vaccines, African swine fever, protective proteins, antibody, cytotoxic T-lymphocytes.

 

Full article (Rus)

Full article (Eng)

 

 

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