Abstract

In vitro neutralizing antibodies have been often correlated with protection against Rift Valley fever virus (RVFV) infection. We have reported previously that a single inoculation of sucrose-purified modified vaccinia Ankara (MVA) encoding RVFV glycoproteins (rMVAGnGc) was sufficient to induce a protective immune response in mice after a lethal RVFV challenge. Protection was related to the presence of glycoprotein specific CD8+ cells, with a low-level detection of in vitro neutralizing antibodies. In this work we extended those observations aimed to explore the role of humoral responses after MVA vaccination and to study the contribution of each glycoprotein antigen to the protective efficacy. Thus, we tested the efficacy and immune responses in BALB/c mice of recombinant MVA viruses expressing either glycoprotein Gn (rMVAGn) or Gc (rMVAGc). In the absence of serum neutralizing antibodies, our data strongly suggest that protection of vaccinated mice upon the RVFV challenge can be achieved by the activation of cellular responses mainly directed against Gc epitopes. The involvement of cellular immunity was stressed by the fact that protection of mice was strain dependent. Furthermore, our data suggest that the rMVA based single dose vaccination elicits suboptimal humoral immune responses against Gn antigen since disease in mice was exacerbated upon virus challenge in the presence of rMVAGnGc or rMVAGn immune serum. Thus, Gc-specific cellular immunity could be an important component in the protection after the challenge observed in BALB/c mice, contributing to the elimination of infected cells reducing morbidity and mortality and counteracting the deleterious effect of a subneutralizing antibody immune response.

Highlights

  • Rift Valley fever virus (RVFV), a mosquito-borne bunyavirus, is widely distributed in Sub-Saharan countries, Egypt and the Arabian Peninsula, causing disease in both humans and livestock [1]

  • Our data suggest that the recombinant MVA (rMVA) based single dose vaccination elicits suboptimal humoral immune responses against Gn antigen since disease in mice was exacerbated upon virus challenge in the presence of rMVAGnGc or recombinant MVA viruses expressing either glycoprotein Gn (rMVAGn) immune serum

  • It was observed that the infection of cells with both recombinant MVAGn and rMVAGc rendered detectable expression levels for both glycoproteins

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Summary

Introduction

Rift Valley fever virus (RVFV), a mosquito-borne bunyavirus, is widely distributed in Sub-Saharan countries, Egypt and the Arabian Peninsula, causing disease in both humans and livestock [1]. The ample range of RVFV competent mosquito vectors present in many areas of the Mediterranean basin suggests that RVF outbreaks in non-endemic areas could potentially end-up in the establishment of enzootic infection cycles [4]. The MVA vector is a highly attenuated version of a vaccinia virus strain that has lost around 30 kb of sequence upon passage in primary avian cells (CEF) so that many host range and immune-modulatory genes are absent or nonfunctional [6]. It has been used in human preclinical and clinical trials [7] and more recently it has been evaluated for different animal diseases, including zoonotic diseases [8]

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