Recombinant vesicular stomatitis virus as an HIV-1 vaccine vector.
Recombinant vesicular stomatitis virus (rVSV) is currently under evaluation as a human immunodeficiency virus (HIV)-1 vaccine vector. The most compelling reasons to develop rVSV as a vaccine vector include a very low seroprevalence in humans, the ability to infect and robustly express foreign antigens in a broad range of cells, and vigorous growth in continuous cell lines used for vaccine manufacture. Numerous preclinical studies with rVSV vectors expressing antigens from a variety of human pathogens have demonstrated the versatility, flexibility, and potential efficacy of the rVSV vaccine platform. When administered to nonhuman primates (NHPs), rVSV vectors expressing HIV-1 Gag and Env elicited robust HIV-1-specific cellular and humoral immune responses, and animals immunized with rVSV vectors expressing simian immunodeficiency virus (SIV) Gag and HIV Env were protected from AIDS after challenge with a pathogenic SIV/HIV recombinant. However, results from an exploratory neurovirulence study in NHPs indicated that these prototypic rVSV vectors might not be adequately attenuated for widespread use in human populations. To address this safety concern, a variety of different attenuation strategies, designed to produce a range of further attenuated rVSV vectors, are currently under investigation. Additional modifications of further attenuated rVSV vectors to upregulate expression of HIV-1 antigens and coexpress molecular adjuvants are also being developed in an effort to balance immunogenicity and attenuation.
Clarke
David K
DK
Department of Vaccines Discovery Research, Wyeth Research, Wyeth, Pearl River, NY 10965, USA.
Cooper
David
D
Egan
Michael A
MA
Hendry
R Michael
RM
Parks
Christopher L
CL
Udem
Stephen A
SA
D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D000276:Adjuvants, Immunologic; D000818:Animals; D023241:Antiretroviral Therapy, Highly Active; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology; D005822:Genetic Vectors; D015488:HIV Antigens / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control; D014614:Vaccines, Synthetic; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D015686:Gene Products, env; D015683:Gene Products, gag; D015488:HIV Antigens; D007155:Immunologic Factors; D014614:Vaccines, Synthetic