Vaccination of mice with replication-defective human immunodeficiency virus induces cellular and humoral immunity and protects against vaccinia virus-gag challenge.
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 were >10(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.
Baliga
Christopher S
CS
Department of Pediatrics, Section of Allergy and Immunology, Baylor College of Medicine, Houston, TX 77030, USA.
van Maanen
Marc
M
Chastain
Michael
M
Sutton
Richard E
RE
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000256:Adenoviridae / Q000235:genetics / Q000276:immunology; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000917:Antibody Formation; D056906:Cyclin T; D016213:Cyclins / Q000235:genetics; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology; D015683:Gene Products, gag / Q000276:immunology*; D005822:Genetic Vectors / Q000276:immunology; D006678:HIV / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D014611:Vaccination; D014616:Vaccinia virus / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology; D014779:Virus Replication
D016915:AIDS Vaccines; D000914:Antibodies, Viral; C503684:CCNT1 protein, human; D056906:Cyclin T; D016213:Cyclins; C028391:G protein, vesicular stomatitis virus; D015683:Gene Products, gag; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins