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- Title
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.
- Authors
López-Gil, Elena; Lorenzo, Gema; Hevia, Esther; Borrego, Belén; Eiden, Martin; Groschup, Martin; Gilbert, Sarah C.; Brun, Alejandro
- 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. Author Summary: Rift Valley fever (RVF) is an important disease of ruminants that affects most African and Arabian Peninsula countries where domestic livestock is the basis for subsistence in rural areas. The disease is caused by a bunyavirus that can be transmitted by close contact with infected animals or through the bite of infected mosquitoes thus facilitating the spread of the virus. Safer and practical methods to control virus spread are demanded in order to prevent both human and animal disease after disease outbreaks. The efficacy of a recombinant modified poxvirus vector (the vaccinia modified Ankara virus (rMVA)) and/or DNA-based vaccines in a mouse infection model has been investigated. A single immunization with a rMVA encoding the virus envelope glycoproteins provided sufficient immunity to protect mice against a lethal dose of RVFV. The immune mechanisms underlying the protection were also investigated. A number of specific immune CD8+-T cells could be activated in the presence of at least three different glycoprotein epitopes. On the other hand, the protective effect of the vaccine was found only in immune competent mice since in mice lacking IFN-type-I responses the vaccine was not efficient.
- Subjects
ANKARA (Turkey); ARABIAN Peninsula; RIFT Valley fever; DNA vaccines; FOOT &; mouth disease; GLYCOPROTEINS; PESTE des petits ruminants; VACCINIA; IMMUNIZATION
- Publication
PLoS Neglected Tropical Diseases, 2013, Vol 7, Issue 7, p1
- ISSN
1935-2727
- Publication type
Article
- DOI
10.1371/journal.pntd.0002309