Abstract
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.
Highlights
Vaccines based on a live, attenuated vesicular stomatitis virus (VSV) platform are being developed for a wide range of infectious diseases and cancer [1,2]
We have reported that activation of murine and human dendritic cells by M51R VSV can be further enhanced by engineering the virus to express the Salmonella enterica fliC gene (M51R-F) [19,27]
This study presents data using nonhuman primates to evaluate dosage and adjuvant function of flagellin when produced by M51R VSV, which has been previously evaluated in mice as a live virus vaccine vector [19]
Summary
Vaccines based on a live, attenuated vesicular stomatitis virus (VSV) platform are being developed for a wide range of infectious diseases and cancer [1,2]. An alternative attenuation strategy is to genetically inactivate the ability of VSV to suppress host antiviral responses. Vaccines 2018, 6, 16 viral matrix (M) protein render the virus unable to suppress host antiviral responses but do not compromise its ability to express viral gene products [12]. M51R VSV induces robust immune responses in mice [18,19]. These properties could be exploited and refined to develop the M51R VSV strain as a live vaccine vector for delivery of heterologous antigens
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