A DNA Vaccine Encoding the Gn Ectodomain of Rift Valley Fever Virus Protects Mice via a Humoral Response Decreased by DEC205 Targeting.

Tiphany Chrun,Matthias Tenbusch,Charles-Adrien Richard,Nicolas Aubrey,Sandra Lacôte,Coralie Pulido,Céline Urien,Isabelle Schwartz-Cornil,Philippe Marianneau,Latifa Lakhdar

doi:10.3389/fimmu.2019.00860

Abstract

The Rift Valley fever virus (RVFV) is responsible for a serious mosquito-borne viral disease in humans and ruminants. The development of a new and safer vaccine is urgently needed due to the risk of introduction of this arbovirus into RVFV-free continents. We recently showed that a DNA vaccine encoding eGn, the ectodomain of the RVFV Gn glycoprotein, conferred a substantial protection in the sheep natural host and that the anti-eGn IgG levels correlated to protection. Addressing eGn to DEC205 reduced the protective efficacy while decreasing the antibody and increasing the IFNγ T cell responses in sheep. In order to get further insight into the involved mechanisms, we evaluated our eGn-encoding DNA vaccine strategy in the reference mouse species. A DNA vaccine encoding eGn induced full clinical protection in mice and the passive transfer of immune serum was protective. This further supports that antibodies, although non-neutralizing in vitro, are instrumental in the protection against RVFV. Addressing eGn to DEC205 was also detrimental to protection in mice, and in this species, both the antibody and the IFNγ T cell responses were strongly decreased. Conversely when using a plasmid encoding a different antigen, i.e., mCherry, DEC205 targeting promoted the antibody response. Altogether our results show that the outcome of targeting antigens to DEC205 depends on the species and on the fused antigen and is not favorable in the case of eGn. In addition, we bring evidences that eGn in itself is a pertinent antigen to be included in a DNA vaccine and that next developments should aim at promoting the anti-eGn antibody response.

Highlights

Rift Valley Fever (RVF) is a mosquito-borne zoonotic viral disease that primarily affects ruminants
We have previously shown that a DNA vaccine encoding eGn administered with a plasmid encoding ovine GM-CSF was efficient at protecting lambs against Rift Valley Fever virus (RVFV), and that the antieGn IgG levels correlated with protection [16]
We showed that a DNA vaccine encoding eGn alone conferred a full protection against a RVFV in mice

Summary

Introduction

Rift Valley Fever (RVF) is a mosquito-borne zoonotic viral disease that primarily affects ruminants. The etiologic agent Rift Valley Fever virus (RVFV) belongs to the Phenuiviridae family and is responsible for a high abortion rate in gravid females, a high mortality rate in newborns, and fetal deformities in domestic ruminants resulting in economic burden [1]. RVFV has spread outside its endemic areas of mainland Africa to Madagascar, the Comoros and the Arabian Peninsula, raising awareness of the risk of introduction and further dissemination of this pathogen into non-endemic continents where a large array of competent mosquitoes can transmit the virus. Commercial attenuated and inactivated veterinary vaccines are available in endemic countries. No safe and efficient vaccine for veterinary and human use is yet available in non-endemic countries [2]

Methods

Results

Conclusion