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

Francisco De La Poza,Alejandro Marín-López,Eva Calvo-Pinilla,Javier Castillo-Olivares,Javier Ortego,Elena López-Gil,Gema Lorenzo,Francisco Mateos,Stephen J Turner

doi:10.1371/journal.pone.0070197

Francisco De La Poza, Alejandro Marín-López + Show 7 more

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https://doi.org/10.1371/journal.pone.0070197

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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.

Highlights

African horse sickness virus (AHSV) is an Orbivirus of the family Reoviridae that causes a severe disease in equids
Labeling was observed on BHK-21 cells transfected with pcDNA3-VP2 and pcDNA3-NS1 by using a serum of mice infected with serotype 4 of AHSV, but not on cells transfected with the control plasmid pcDNA3 (Fig. 1)
These data confirmed the efficient expression of the proteins from AHSV-4 cloned in the DNA and Modified vaccinia virus Ankara (MVA) vaccine vectors used for immunization of IFNAR(2/2) mice

Summary

Introduction

African horse sickness virus (AHSV) is an Orbivirus of the family Reoviridae that causes a severe disease in equids. African horse sickness (AHS) is mostly confined to sub-Saharan Africa, there are sporadic outbreaks in North Africa, Pakistan, India, Portugal and Spain [1]. The genus Orbivirus includes bluetongue virus (BTV) and epizootic haemorrhagic disease virus (EHDV), which have similar morphological and biochemical properties but affect different hosts. AHSV is transmitted by Culicoides midges [1,4], the same insect vectors as those that transmit BTV. Since 2008 there has been a dramatic northward spread of BTV in Europe related with the extension of the insect’s habitat due to climate change. The presence of insect vectors in Europe increases the probability that outbreaks of AHS may follow [5]

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