A single immunization with MVA expressing GnGc glycoproteins promotes epitope-specific CD8+-T cell activation and protects immune-competent mice against a lethal RVFV infection.

Abstract

BACKGROUND:

Rift Valley fever virus (RVFV) is a mosquito-borne pathogen causing an important disease in ruminants often transmitted to humans after epizootic outbreaks in African and Arabian countries. To help combat the spread of the disease, prophylactic measures need to be developed and/or improved.

METHODOLOGY/PRINCIPAL FINDINGS:

In this work, we evaluated the immunogenicity and protective efficacy of recombinant plasmid DNA and modified vaccinia virus Ankara (rMVA) vectored vaccines against Rift Valley fever in mice. These recombinant vaccines encoded either of two components of the Rift Valley fever virus: the viral glycoproteins (Gn/Gc) or the nucleoprotein (N). Following lethal challenge with live RVFV, mice immunized with a single dose of the rMVA-Gn/Gc vaccine showed no viraemia or clinical manifestation of disease, but mounted RVFV neutralizing antibodies and glycoprotein specific CD8+ T-cell responses. Neither DNA-Gn/Gc alone nor a heterologous prime-boost immunization schedule (DNA-Gn/Gc followed by rMVAGn/Gc) was better than the single rMVA-Gn/Gc immunization schedule with regards to protective efficacy. However, the rMVA-Gn/Gc vaccine failed to protect IFNAR(-/-) mice upon lethal RVFV challenge suggesting a role for innate responses in protection against RVFV. Despite induction of high titer antibodies against the RVFV nucleoprotein, the rMVA-N vaccine, whether in homologous or heterologous prime-boost schedules with the corresponding recombinant DNA vaccine, only conferred partial protection to RVFV challenge.

CONCLUSIONS/SIGNIFICANCE:

Given the excellent safety profile of rMVA based vaccines in humans and animals, our data supports further development of rMVA-Gn/Gc as a vaccine strategy that can be used for the prevention of Rift Valley fever in both humans and livestock.

• Authors: Elena López-Gil, Gema Lorenzo, Esther Hevia, Belén Borrego, Martin Eiden, Martin Groschup, Sarah C Gilbert, Alejandro Brun
• Journal: PLoS neglected tropical diseases (PLoS Negl Trop Dis) Vol. 7 Issue 7 Pg. e2309 ( 2013) ISSN: 1935-2735 [Electronic] United States
• PMID: 23875044 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Neutralizing
• Antibodies, Viral
• Drug Carriers
• Epitopes
• Glycoproteins
• Vaccines, DNA
• Vaccines, Synthetic
• Viral Proteins
• Viral Vaccines
• Receptor, Interferon alpha-beta

Topics

• Animals
• Antibodies, Neutralizing (blood)
• Antibodies, Viral (blood)
• CD8-Positive T-Lymphocytes (immunology)
• Disease Models, Animal
• Drug Carriers
• Epitopes (immunology)
• Female
• Glycoproteins (immunology)
• Mice
• Mice, Inbred BALB C
• Mice, Knockout
• Receptor, Interferon alpha-beta (deficiency)
• Rift Valley Fever (immunology, mortality, pathology, prevention & control)
• Rift Valley fever virus (immunology)
• Survival Analysis
• Vaccines, DNA (administration & dosage, immunology)
• Vaccines, Synthetic (administration & dosage, immunology)
• Vaccinia virus (genetics)
• Viral Proteins (immunology)
• Viral Vaccines (administration & dosage, immunology)
• Viremia (prevention & control)