First Human Trial of a DNA-Based Vaccine for Treatment of Human Immunodeficiency Virus Type 1 Infection: Safety and Host Response

• Published in: The Journal of infectious diseases 1998-07, Vol.178 (1), p.92-100
• Main Authors: MacGregor, Rob Roy, Boyer, Jean D., Ugen, Kenneth E., Lacy, Kim E., Gluckman, Stephen J., Bagarazzi, Mark L., Chattergoon, Michael A., Baine, Yaela, Higgins, Terry J., Ciccarelli, Richard B., Coney, Leslie R., Ginsberg, Richard S., Weiner, David B.
• Format: Article
• Language: English
• Subjects: Adult; AIDS; AIDS Vaccines - administration & dosage; AIDS Vaccines - adverse effects; AIDS Vaccines - therapeutic use; AIDS/HIV; Antibodies; Biological and medical sciences; CD4 Lymphocyte Count; Dosage; Female; Fundamental and applied biological sciences. Psychology; Genes, env; Genes, rev; HIV; HIV 1; HIV Antibodies - blood; HIV Antibodies - immunology; HIV Envelope Protein gp120 - immunology; HIV Infections - immunology; HIV Infections - therapy; HIV Infections - virology; HIV-1 - genetics; HIV-1 - immunology; HIV-1 - physiology; Humans; Immunization Schedule; Infections; Lymphocyte Activation; Lymphocyte Count; Lymphocytes; Major Articles; Male; Microbiology; Middle Aged; RNA; RNA, Viral - blood; Semen - virology; T-Lymphocytes, Cytotoxic - immunology; Vaccination; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Vaccines, DNA - administration & dosage; Vaccines, DNA - adverse effects; Vaccines, DNA - therapeutic use; Virology; Viruses
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/515613

A DNA-based vaccine containing human immunodeficiency virus type 1 (HIV-1) env and rev genes was tested for safety and host immune response in 15 asymptomatic HIV-infected patients who were not using antiviral drugs and who had CD4+ lymphocyte counts of ⩾500 per microliter of blood. Successive groups received three doses of vaccine (30, 100, or 300 µg) at 10-week intervals in a dose-escalation trial. Vaccine administration induced no local or systemic reactions, and no laboratory abnormalities were detected. Specifically, no patient developed anti-DNA antibody or muscle enzyme elevations. No consistent change occurred in CD4 or CD8 lymphocyte counts or in plasma HIV concentration. Antibody against gp120 increased in individual patients in the 100- and 300-µg groups. Some increases were noted in cytotoxic T lymphocyte activity against gp160-bearing targets and in lymphocyte proliferative activity. The safety and potential immunogenicity of an HIV-directed DNA-based vaccine was demonstrated, a finding that should encourage further studies.