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HIV-specific humoral responses benefit from stronger prime in phase Ib clinical trial.

Publication ,  Journal Article
Bart, P-A; Huang, Y; Karuna, ST; Chappuis, S; Gaillard, J; Kochar, N; Shen, X; Allen, MA; Ding, S; Hural, J; Liao, H-X; Haynes, BF; Frahm, N ...
Published in: J Clin Invest
November 2014

BACKGROUND. Vector prime-boost immunization strategies induce strong cellular and humoral immune responses. We examined the priming dose and administration order of heterologous vectors in HIV Vaccine Trials Network 078 (HVTN 078), a randomized, double-blind phase Ib clinical trial to evaluate the safety and immunogenicity of heterologous prime-boost regimens, with a New York vaccinia HIV clade B (NYVAC-B) vaccine and a recombinant adenovirus 5-vectored (rAd5-vectored) vaccine. METHODS. NYVAC-B included HIV-1 clade B Gag-Pol-Nef and gp120, while rAd5 included HIV-1 clade B Gag-Pol and clades A, B, and C gp140. Eighty Ad5-seronegative subjects were randomized to receive 2 × NYVAC-B followed by 1 × 1010 PFU rAd5 (NYVAC/Ad5hi); 1 × 108 PFU rAd5 followed by 2 × NYVAC-B (Ad5lo/NYVAC); 1 × 109 PFU rAd5 followed by 2 × NYVAC-B (Ad5med/NYVAC); 1 × 1010 PFU rAd5 followed by 2 × NYVAC-B (Ad5hi/NYVAC); or placebo. Immune responses were assessed 2 weeks after the final vaccination. Intracellular cytokine staining measured T cells producing IFN-γ and/or IL-2; cross-clade and epitope-specific binding antibodies were determined; and neutralizing antibodies (nAbs) were assessed with 6 tier 1 viruses. RESULTS. CD4+ T cell response rates ranged from 42.9% to 93.3%. NYVAC/Ad5hi response rates (P ≤ 0.01) and magnitudes (P ≤ 0.03) were significantly lower than those of other groups. CD8+ T cell response rates ranged from 65.5% to 85.7%. NYVAC/Ad5hi magnitudes were significantly lower than those of other groups (P ≤ 0.04). IgG response rates to the group M consensus gp140 were 89.7% for NYVAC/Ad5hi and 21.4%, 84.6%, and 100% for Ad5lo/NYVAC, Ad5med/NYVAC, and Ad5hi/NYVAC, respectively, and were similar for other vaccine proteins. Overall nAb responses were low, but aggregate responses appeared stronger for Ad5med/NYVAC and Ad5hi/NYVAC than for NYVAC/Ad5hi. CONCLUSIONS. rAd5 prime followed by NYVAC boost is superior to the reverse regimen for both vaccine-induced cellular and humoral immune responses. Higher Ad5 priming doses significantly increased binding and nAbs. These data provide a basis for optimizing the design of future clinical trials testing vector-based heterologous prime-boost strategies. TRIAL REGISTRATION. ClinicalTrials.gov NCT00961883. FUNDING. NIAID, NIH UM1AI068618, AI068635, AI068614, and AI069443.

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Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

November 2014

Volume

124

Issue

11

Start / End Page

4843 / 4856

Location

United States

Related Subject Headings

  • Young Adult
  • Vaccination
  • Protein Binding
  • Male
  • Immunology
  • Immunoglobulin G
  • Immunization, Secondary
  • Immunity, Humoral
  • Immunity, Cellular
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Bart, P.-A., Huang, Y., Karuna, S. T., Chappuis, S., Gaillard, J., Kochar, N., … Frahm, N. (2014). HIV-specific humoral responses benefit from stronger prime in phase Ib clinical trial. J Clin Invest, 124(11), 4843–4856. https://doi.org/10.1172/JCI75894
Bart, Pierre-Alexandre, Yunda Huang, Shelly T. Karuna, Samuel Chappuis, Julien Gaillard, Nidhi Kochar, Xiaoying Shen, et al. “HIV-specific humoral responses benefit from stronger prime in phase Ib clinical trial.J Clin Invest 124, no. 11 (November 2014): 4843–56. https://doi.org/10.1172/JCI75894.
Bart P-A, Huang Y, Karuna ST, Chappuis S, Gaillard J, Kochar N, et al. HIV-specific humoral responses benefit from stronger prime in phase Ib clinical trial. J Clin Invest. 2014 Nov;124(11):4843–56.
Bart, Pierre-Alexandre, et al. “HIV-specific humoral responses benefit from stronger prime in phase Ib clinical trial.J Clin Invest, vol. 124, no. 11, Nov. 2014, pp. 4843–56. Pubmed, doi:10.1172/JCI75894.
Bart P-A, Huang Y, Karuna ST, Chappuis S, Gaillard J, Kochar N, Shen X, Allen MA, Ding S, Hural J, Liao H-X, Haynes BF, Graham BS, Gilbert PB, McElrath MJ, Montefiori DC, Tomaras GD, Pantaleo G, Frahm N. HIV-specific humoral responses benefit from stronger prime in phase Ib clinical trial. J Clin Invest. 2014 Nov;124(11):4843–4856.

Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

November 2014

Volume

124

Issue

11

Start / End Page

4843 / 4856

Location

United States

Related Subject Headings

  • Young Adult
  • Vaccination
  • Protein Binding
  • Male
  • Immunology
  • Immunoglobulin G
  • Immunization, Secondary
  • Immunity, Humoral
  • Immunity, Cellular
  • Humans