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Immunogenicity in African Green Monkeys of M Protein Mutant Vesicular Stomatitis Virus Vectors and Contribution of Vector-Encoded Flagellin

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Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston Salem, NC 27101, USA
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Department of Biochemistry, Wake Forest School of Medicine, Winston Salem, NC 27101, USA
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Department of Pathology, Section of Comparative Medicine, Wake Forest School of Medicine, Winston Salem, NC 27101, USA
*
Author to whom correspondence should be addressed.
Vaccines 2018, 6(1), 16; https://doi.org/10.3390/vaccines6010016
Received: 26 February 2018 / Revised: 16 March 2018 / Accepted: 18 March 2018 / Published: 19 March 2018
Recombinant vesicular stomatitis virus (VSV) is a promising platform for vaccine development. M51R VSV, an attenuated, M protein mutant strain, is an effective inducer of Type I interferon and dendritic cell (DC) maturation, which are desirable properties to exploit for vaccine design. We have previously evaluated M51R VSV (M51R) and M51R VSV that produces flagellin (M51R-F) as vaccine vectors using murine models, and found that flagellin enhanced DC activation and VSV-specific antibody production after low-dose vaccination. In this report, the immunogenicity of M51R vectors and the adjuvant effect of virus-produced flagellin were evaluated in nonhuman primates following high-dose (108 pfu) and low-dose (105 pfu) vaccination. A single intramuscular vaccination of African green monkeys with M51R or M51R-F induced VSV-specific, dose-dependent humoral immune responses. Flagellin induced a significant increase in antibody production (IgM, IgG and neutralizing antibody) at the low vaccination dose. A VSV-specific cellular response was detected at 6 weeks post-vaccination, but was neither dose-dependent nor enhanced by flagellin; similar numbers of VSV-specific, IFNγ-producing cells were detected in lymph node and spleen of all animals. These results indicate that virus-directed, intracellular flagellin production may improve VSV-based vaccines encoding heterologous antigens by lowering the dose required to achieve humoral immunity. View Full-Text
Keywords: vesicular stomatitis virus; vaccine; vector; flagellin; nonhuman primate; African green monkey vesicular stomatitis virus; vaccine; vector; flagellin; nonhuman primate; African green monkey
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Westcott, M.M.; Smedberg, J.; Jorgensen, M.J.; Puckett, S.; Lyles, D.S. Immunogenicity in African Green Monkeys of M Protein Mutant Vesicular Stomatitis Virus Vectors and Contribution of Vector-Encoded Flagellin. Vaccines 2018, 6, 16.

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