1. Vaccination of Mice with Replication-Defective Human Immunodeficiency Virus Induces Cellular and Humoral Immunity and Protects against Vaccinia Virus-gag Challenge
- Author
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Richard E. Sutton, Christopher S. Baliga, Michael Chastain, and Marc van Maanen
- Subjects
viruses ,Genetic Vectors ,Cytomegalovirus ,Gene Products, gag ,Vaccinia virus ,Antibodies, Viral ,Virus Replication ,Virus ,Adenoviridae ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Viral Envelope Proteins ,Interferon ,Cyclins ,Drug Discovery ,Genetics ,medicine ,Animals ,Humans ,Molecular Biology ,030304 developmental biology ,AIDS Vaccines ,Pharmacology ,Immunity, Cellular ,0303 health sciences ,Membrane Glycoproteins ,biology ,Cyclin T ,ELISPOT ,Vaccination ,030302 biochemistry & molecular biology ,Antibody titer ,HIV ,biology.organism_classification ,Virology ,3. Good health ,chemistry ,Vesicular stomatitis virus ,Antibody Formation ,Humoral immunity ,biology.protein ,Molecular Medicine ,Vaccinia ,Antibody ,medicine.drug - Abstract
Here we describe as a potential vaccine candidate a replication-defective HIV that encodes multiple viral genes in addition to a cassette that includes both truncated cyclin T1 and an autofluorescent protein. After confirming functionality of the cyclin T1, we immunized mice intramuscularly once or twice with the replication-defective HIV vector pseudotyped with vesicular stomatitis virus (VSV) G protein (RD HIV), a plasmid encoding CMV-driven gag (gag DNA), or adenovirus gag (Ad5-gag). Capsid-specific antibody titers following RD HIV immunization were10(6)/ml and approximately equivalent to those induced by gag DNA and Ad5-gag. Antibodies against the autofluorescent protein and VSV G were also detected. After RD HIV immunization ELISpot assays demonstrated Gag-specific interferon-gamma (IFN-gamma) SFU equivalent to that of Ad5-gag and fourfold greater than that of gag DNA. HIV polymerase-specific IFN-gamma SFU values were similar, and boosting increased both antibody titers and the IFN-gamma response. Challenge using vaccinia virus (VV)-gag demonstrated significantly lower recoverable VV for RD HIV-immunized mice compared to controls. No significant differences were observed in vaccinated mice challenged with wild-type VV. This study demonstrates the efficacy of RD HIV in conferring HIV-specific immunity and protection in mice and suggests its potential use in humans as either a prophylactic or a therapeutic vaccine.
- Published
- 2006
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