Immunogenicity in African Green Monkeys of M Protein Mutant Vesicular Stomatitis Virus Vectors and Contribution of Vector-Encoded Flagellin
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 previ...
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| Format: | Article |
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MDPI AG
2018-03-01
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| Series: | Vaccines |
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| Online Access: | http://www.mdpi.com/2076-393X/6/1/16 |
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| author | Marlena M. Westcott Jason Smedberg Matthew J. Jorgensen Shelby Puckett Douglas S. Lyles |
| author_facet | Marlena M. Westcott Jason Smedberg Matthew J. Jorgensen Shelby Puckett Douglas S. Lyles |
| author_sort | Marlena M. Westcott |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T13:24:36Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-04-11T13:24:36Z |
| publishDate | 2018-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-537fe82536104415877ff3f27c33f6862022-12-22T04:22:07ZengMDPI AGVaccines2076-393X2018-03-01611610.3390/vaccines6010016vaccines6010016Immunogenicity in African Green Monkeys of M Protein Mutant Vesicular Stomatitis Virus Vectors and Contribution of Vector-Encoded FlagellinMarlena M. Westcott0Jason Smedberg1Matthew J. Jorgensen2Shelby Puckett3Douglas S. Lyles4Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston Salem, NC 27101, USADepartment of Biochemistry, Wake Forest School of Medicine, Winston Salem, NC 27101, USADepartment of Pathology, Section of Comparative Medicine, Wake Forest School of Medicine, Winston Salem, NC 27101, USADepartment of Biochemistry, Wake Forest School of Medicine, Winston Salem, NC 27101, USADepartment of Biochemistry, Wake Forest School of Medicine, Winston Salem, NC 27101, USARecombinant 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.http://www.mdpi.com/2076-393X/6/1/16vesicular stomatitis virusvaccinevectorflagellinnonhuman primateAfrican green monkey |
| spellingShingle | Marlena M. Westcott Jason Smedberg Matthew J. Jorgensen Shelby Puckett Douglas S. Lyles Immunogenicity in African Green Monkeys of M Protein Mutant Vesicular Stomatitis Virus Vectors and Contribution of Vector-Encoded Flagellin Vaccines vesicular stomatitis virus vaccine vector flagellin nonhuman primate African green monkey |
| title | Immunogenicity in African Green Monkeys of M Protein Mutant Vesicular Stomatitis Virus Vectors and Contribution of Vector-Encoded Flagellin |
| title_full | Immunogenicity in African Green Monkeys of M Protein Mutant Vesicular Stomatitis Virus Vectors and Contribution of Vector-Encoded Flagellin |
| title_fullStr | Immunogenicity in African Green Monkeys of M Protein Mutant Vesicular Stomatitis Virus Vectors and Contribution of Vector-Encoded Flagellin |
| title_full_unstemmed | Immunogenicity in African Green Monkeys of M Protein Mutant Vesicular Stomatitis Virus Vectors and Contribution of Vector-Encoded Flagellin |
| title_short | Immunogenicity in African Green Monkeys of M Protein Mutant Vesicular Stomatitis Virus Vectors and Contribution of Vector-Encoded Flagellin |
| title_sort | immunogenicity in african green monkeys of m protein mutant vesicular stomatitis virus vectors and contribution of vector encoded flagellin |
| topic | vesicular stomatitis virus vaccine vector flagellin nonhuman primate African green monkey |
| url | http://www.mdpi.com/2076-393X/6/1/16 |
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