4.5 Article

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

Journal

VACCINE
Volume 26, Issue 8, Pages 1098-1110

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2007.12.024

Keywords

HIV-1; DNA vaccine; recombinant protein vaccine; phase I clinical trial; prime-boost

Funding

  1. Intramural NIH HHS [Z01 AI000883-07] Funding Source: Medline
  2. NIAID NIH HHS [R01AI65250, AI30034, R01 AI065250, R21 AI046294, R21 AI046294-02, R29 AI040337-05, R29AI40337, AI46705, N01AI05394, R01 AI065250-02] Funding Source: Medline
  3. NIAID NIH HHS [R21 AI046294, N01AI30034, AI46705, R29AI40337, R29 AI040337, N01AI05394, R01 AI065250, R21 AI046294, R01AI65250] Funding Source: Medline
  4. NIDDK NIH HHS [5P30DK32520, P30 DK032520] Funding Source: Medline
  5. NIDDK NIH HHS [P30 DK032520, 5P30DK32520] Funding Source: Medline

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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 conducted in healthy adult volunteers of both genders. Robust cross-subtype HIV-1-specific T cell responses were detected in IFN gamma 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 potyvatent Env formulation could generate broad immune responses against HIV-1 viruses with diverse genetic backgrounds. (c) 2008 Elsevier Ltd. All rights reserved.

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