Ns1 Is a Key Protein in the Vaccine Composition to Protect Ifnar(−/−) Mice against Infection with Multiple Serotypes of African Horse Sickness Virus

Abstract

African horse sickness virus (AHSV) belongs to the genus Orbivirus. We have now engineered naked DNAs and recombinant modified vaccinia virus Ankara (rMVA) expressing VP2 and NS1 proteins from AHSV-4. IFNAR(−/−) mice inoculated with DNA/rMVA-VP2,-NS1 from AHSV-4 in an heterologous prime-boost vaccination strategy generated significant levels of neutralizing antibodies specific of AHSV-4. In addition, vaccination stimulated specific T cell responses against the virus. The vaccine elicited partial protection against an homologous AHSV-4 infection and induced cross-protection against the heterologous AHSV-9. Similarly, IFNAR(−/−) mice vaccinated with an homologous prime-boost strategy with rMVA-VP2-NS1 from AHSV-4 developed neutralizing antibodies and protective immunity against AHSV-4. Furthermore, the levels of immunity were very high since none of vaccinated animals presented viraemia when they were challenged against the homologous AHSV-4 and very low levels when they were challenged against the heterologous virus AHSV-9. These data suggest that the immunization with rMVA/rMVA was more efficient in protection against a virulent challenge with AHSV-4 and both strategies, DNA/rMVA and rMVA/rMVA, protected against the infection with AHSV-9. The inclusion of the protein NS1 in the vaccine formulations targeting AHSV generates promising multiserotype vaccines.

An experimental subunit vaccine based on Bluetongue virus 4 VP2 protein fused to an antigen-presenting cells single chain antibody elicits cellular and humoral immune responses in cattle, guinea pigs and IFNAR(−/−) mice

“…Serum NAs were detected by the virus neutralization assay [27]. Differences in antibody titers among experimental groups were evaluated by ANOVA under a model of repeated measures throughout time, followed by a general contrast post-ANOVA test.…”

Antiserum from mice vaccinated with modified vaccinia Ankara virus expressing African horse sickness virus (AHSV) VP2 provides protection when it is administered 48h before, or 48h after challenge

“…Recently, cell-mediated immune responses have been detected in horses following inoculation with live attenuated AHSV vaccines (Pretorius et al, 2012), or recombinant Canarypox virus expressing AHSV VP2 and VP5 (El Garch et al, 2012). More recently, cell-mediated immune responses have also been observed in interferon alpha receptor gene knock-out mice (IFNAR À/À) after vaccination with single MVA recombinant viruses expressing AHSV VP2 or NS1 (de la Poza et al, 2013). Since cellular immunity has been associated with protection against BTV, it is generally assumed that the same applies to AHSV.…”

Immunoinformatics Prediction of Peptide-Based Vaccine Against African Horse Sickness Virus

“…(AHSV) is a double-stranded RNA (dsRNA) virus with ten genome segments encoding seven structural proteins (VP1-VP7) and four non-structural proteins (NS1, NS2, NS3, NS3A) [1,6]. There are two major outer capsid structural proteins in the African horse sickness virus; (VP2) and (VP5) [10,17]. (VP2) is the major protective antigen of (AHSV) that is responsible for the serotype formation.…”

“…(VP2) is the major protective antigen of (AHSV) that is responsible for the serotype formation. The majority of neutralizing epitopes are located on (VP2) which can be considered as the main target of immune response to the virus [11][12][13]17,18].…”

“…In addition, serotypes 5 and 9 are normally excluded from the (LAV) formulations as serotype 5 is difficult to attenuate and partially crossreacts with serotype 8 and serotype 9 partially cross-reacts with serotype 6 [1,9,11,12,[19][20][21]. A recent Approach applied is the recombinant technology that was used in the development of recombinant modified vaccinia ankara (MVA-VP2) vaccine which is highly protective against (AHSV), but the scale of it is limited to only two serotypes; (AHSV-4) and (AHSV-9) [5,9,10,13,17,18,22]. Therefore, it is important to consider alternative approaches for (AHSV) vaccine development.…”