Cross-subtype antibody and cellular immune responses induced by a polyvalent DNA prime–protein boost HIV-1 vaccine in healthy human volunteers

• Published in: Vaccine 2008-07, Vol.26 (31), p.3947-3957
• Main Authors: Wang, Shixia, Kennedy, Jeffrey S, West, Kim, Montefiori, David C, Coley, Scott, Lawrence, John, Shen, Siyuan, Green, Sharone, Rothman, Alan L, Ennis, Francis A, Arthos, James, Pal, Ranajit, Markham, Phillip, Lu, Shan
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; Adolescent; Adult; AIDS; AIDS Vaccines - immunology; Allergy and Immunology; Antigens; Clinical trials; Cross Reactions; Deoxyribonucleic acid; DNA; DNA vaccine; Female; HIV; HIV Antibodies - blood; HIV-1; HIV-1 - immunology; Human Experimentation; Human immunodeficiency virus; Humans; Immunization; Immunization, Secondary; Interferon-gamma - metabolism; Male; Middle Aged; Neutralization Tests; Phase I clinical trial; Plasmids; Prime–boost; Proteins; Recombinant protein vaccine; Studies; T-Lymphocytes - immunology; Vaccines; Vaccines, DNA - immunology; Vaccines, Subunit - immunology
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2007.12.060

Abstract An optimally effective AIDS vaccine would likely require the induction of both neutralizing antibody and cell-mediated immune responses, which has proven difficult to obtain in previous clinical trials. Here we report on the induction of human immunodeficiency virus type-1 (HIV-1)-specific immune responses in healthy adult volunteers that received the multi-gene, polyvalent, DNA prime–protein boost HIV-1 vaccine formulation, DP6-001, in a Phase I clinical trial. Robust cross-subtype HIV-1-specific T cell responses were detected in IFN-γ ELISPOT assays. Furthermore, we detected high titer serum antibody responses that recognized a wide range of primary HIV-1 Env antigens and also neutralized pseudotyped viruses that express the primary Env antigens from multiple HIV-1 subtypes. These findings demonstrate that the DNA prime–protein boost approach is an effective immunization method to elicit both humoral and cell-mediated immune responses in humans, and that a polyvalent Env formulation could generate broad immune responses against HIV-1 viruses with diverse genetic backgrounds.