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Modification of the Association Between T-Cell Immune Responses and Human Immunodeficiency Virus Type 1 Infection Risk by Vaccine-Induced Antibody Responses in the HVTN 505 Trial.

Publication ,  Journal Article
Fong, Y; Shen, X; Ashley, VC; Deal, A; Seaton, KE; Yu, C; Grant, SP; Ferrari, G; deCamp, AC; Bailer, RT; Koup, RA; Montefiori, D; Haynes, BF ...
Published in: J Infect Dis
March 28, 2018

BACKGROUND: HVTN 505 was a human immunodeficiency virus type 1 (HIV-1) preventive vaccine efficacy trial of a DNA/recombinant adenovirus serotype 5 (rAd5) vaccine regimen. We assessed antibody responses measured 1 month after final vaccination (month 7) as correlates of HIV-1 acquisition risk. METHODS: Binding antibody responses were quantified in serum samples from 25 primary endpoint vaccine cases (diagnosed with HIV-1 infection between month 7 and month 24) and 125 randomly sampled frequency-matched vaccine controls (HIV-1 negative at month 24). We prespecified for a primary analysis tier 6 antibody response biomarkers that measure immunoglobulin G (IgG) and immunoglobulin A (IgA) binding to Env proteins and 2 previously assessed T-cell response biomarkers. RESULTS: Envelope-specific IgG responses were significantly correlated with decreased HIV-1 risk. Moreover, the interaction of IgG responses and Env-specific CD8+ T-cell polyfunctionality score had a highly significant association with HIV-1 risk after adjustment for multiple comparisons. CONCLUSIONS: Vaccinees with higher levels of Env IgG have significantly decreased HIV-1 risk when CD8+ T-cell responses are low. Moreover, vaccinees with high CD8+ T-cell responses generally have low risk, and those with low CD8+ T-cell and low Env antibody responses have high risk. These findings suggest the critical importance of inducing a robust IgG Env response when the CD8+ T-cell response is low.

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Published In

J Infect Dis

DOI

EISSN

1537-6613

Publication Date

March 28, 2018

Volume

217

Issue

8

Start / End Page

1280 / 1288

Location

United States

Related Subject Headings

  • Microbiology
  • Male
  • Immunoglobulin G
  • Humans
  • HIV-1
  • HIV Infections
  • HIV Antibodies
  • CD8-Positive T-Lymphocytes
  • Antibody Formation
  • AIDS Vaccines
 

Citation

APA
Chicago
ICMJE
MLA
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Fong, Y., Shen, X., Ashley, V. C., Deal, A., Seaton, K. E., Yu, C., … Tomaras, G. D. (2018). Modification of the Association Between T-Cell Immune Responses and Human Immunodeficiency Virus Type 1 Infection Risk by Vaccine-Induced Antibody Responses in the HVTN 505 Trial. J Infect Dis, 217(8), 1280–1288. https://doi.org/10.1093/infdis/jiy008
Fong, Youyi, Xiaoying Shen, Vicki C. Ashley, Aaron Deal, Kelly E. Seaton, Chenchen Yu, Shannon P. Grant, et al. “Modification of the Association Between T-Cell Immune Responses and Human Immunodeficiency Virus Type 1 Infection Risk by Vaccine-Induced Antibody Responses in the HVTN 505 Trial.J Infect Dis 217, no. 8 (March 28, 2018): 1280–88. https://doi.org/10.1093/infdis/jiy008.
Fong Y, Shen X, Ashley VC, Deal A, Seaton KE, Yu C, Grant SP, Ferrari G, deCamp AC, Bailer RT, Koup RA, Montefiori D, Haynes BF, Sarzotti-Kelsoe M, Graham BS, Carpp LN, Hammer SM, Sobieszczyk M, Karuna S, Swann E, DeJesus E, Mulligan M, Frank I, Buchbinder S, Novak RM, McElrath MJ, Kalams S, Keefer M, Frahm NA, Janes HE, Gilbert PB, Tomaras GD. Modification of the Association Between T-Cell Immune Responses and Human Immunodeficiency Virus Type 1 Infection Risk by Vaccine-Induced Antibody Responses in the HVTN 505 Trial. J Infect Dis. 2018 Mar 28;217(8):1280–1288.
Journal cover image

Published In

J Infect Dis

DOI

EISSN

1537-6613

Publication Date

March 28, 2018

Volume

217

Issue

8

Start / End Page

1280 / 1288

Location

United States

Related Subject Headings

  • Microbiology
  • Male
  • Immunoglobulin G
  • Humans
  • HIV-1
  • HIV Infections
  • HIV Antibodies
  • CD8-Positive T-Lymphocytes
  • Antibody Formation
  • AIDS Vaccines