Single Dose Trivalent Vesiculovax Vaccine Protects Macaques from Lethal Ebolavirus and Marburgvirus Challenge.

Single Dose Trivalent Vesiculovax Vaccine Protects Macaques from Lethal Ebolavirus and Marburgvirus Challenge.

J Virol. 2017 Nov 15;:

Authors: Matassov D, Mire CE, Latham T, Geisbert JB, Xu R, Ota-Setlik A, Agans KN, Kobs DJ, Wendling MQS, Burnaugh A, Rudge TL, Sabourin CL, Egan MA, Clarke DK, Geisbert TW, Eldridge JH

Abstract
Previous studies demonstrated that a single intramuscular (IM) dose of an attenuated vesicular stomatitis virus vector (Vesiculovax™, rVSV-N4CT1) expressing the glycoprotein (GP) from the Mayinga strain of Zaire ebolavirus (EBOV) protected nonhuman primates (NHP) from lethal challenge with EBOV Kikwit and Makona strains. Here we studied the immunogenicity of an expanded range of attenuated rVSV vectors expressing filovirus GP in mice. Based on data from those studies an optimal attenuated tri-valent rVSV vector formulation was identified which included rVSV vectors expressing EBOV, Sudan ebolavirus (SUDV) or Angola strain of Marburg marburgvirus (MARV) GPs. NHPs were then vaccinated with a single dose of the tri-valent formulation, followed by lethal challenge 28 days later with each of the three corresponding filoviruses. At day 14 post vaccination, a serum IgG response specific for all three GPs was detected in all vaccinated macaques. A modest and balanced cell-mediated immune response specific for each GP protein was also detected in a majority of vaccinated macaques. No matter the level of total GP-specific immune response detected post vaccination, all vaccinated macaques were protected from disease and death following lethal challenge with each of the three filoviruses. These findings indicate that vaccination with a single dose of attenuated rVSV-N4CT1 vectors each expressing a single filovirus GP may provide protection against those filoviruses most commonly responsible for outbreaks of hemorrhagic fever in sub-Saharan Africa.IMPORTANCE The West African Ebola Zaire outbreak in 2013 showed that this disease was not only a regional concern, but a worldwide problem and highlighted the need for a safe and efficacious vaccine to be administered to the populace. However, other endemic pathogens like Ebola Sudan and Marburg also pose an important health risk to the public and therefore require development of a vaccine prior to the occurrence of an outbreak. The significance of our research was the development of a blended tri-valent filovirus vaccine that would elicit a balanced immune response when administered as a single dose and provide complete protection against a lethal challenge of all three filovirus pathogens.

PMID: 29142131 [PubMed - as supplied by publisher]

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