Phase 2 study of an HIV-1 canarypox vaccine (vCP1452) alone and in combination with rgp120: Negative results fail to trigger a phase 3 correlates trial

Nina D. Russell, Barney S. Graham, Michael C. Keefer, M. Juliana McElrath, Steve G. Self, Kent J. Weinhold, David C. Montefiori, Guido Ferrari, Helen Horton, Georgia D. Tomaras, Sanjay Gurunathan, Lynn Baglyos, Sharon E. Frey, Mark J. Mulligan, Clayton D. Harro, Susan P. Buchbinder, Lindsey R. Baden, William A. Blattner, Beryl A. Koblin, Lawrence Corey

Research output: Contribution to journalArticle

Abstract

BACKGROUND: A goal of T-cell HIV vaccines is to define the correlation between a vaccine-induced immune response and protection from HIV infection. We conducted a phase 2 trial to determine if a canarypox vaccine candidate (vCP1452) administered with rgp120 subunit protein would "qualify" for a trial to define a correlate of efficacy. METHODS: A total of 330 healthy volunteers were enrolled into 4 groups: 120 received vCP1452 alone (0, 1, 3, and 6 months), 120 received vCP1452 with 2 different regimens of rgp120 coadministration, and 90 received placebo. HIV-specific antibody responses were measured by enzyme-linked immunoassay (ELISA) and neutralizing activity. T-cell responses were measured by chromium release and interferon-γ (IFNγ) enzyme-linked immunospot (ELISpot) assay. RESULTS: Significant neutralizing antibody responses to the HIV MN strain were detected in all vaccine groups, with net responses ranging from 57% (95% confidence interval [CI]: 40% to 71%) to 94% (95% CI: 85% to 99%). Net cumulative HIV-specific CD8 IFNγ ELISpot assay responses were 13% (95% CI: -1% to 26%) for recipients of vCP1452 alone and 16% (95% CI: 2% to 29%) for recipients of vCP1452 plus rgp120. CONCLUSIONS: Overall, the HIV-specific CD8 cytotoxic T lymphocyte (CTL) response was not sufficient to qualify the regimen for a subsequent trial designed to detect an immune correlate of protection requiring a minimum CD8 CTL frequency of 30%.

Original languageEnglish (US)
Pages (from-to)203-212
Number of pages10
JournalJournal of Acquired Immune Deficiency Syndromes
Volume44
Issue number2
DOIs
StatePublished - Feb 2007

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HIV-1
Vaccines
Confidence Intervals
Enzyme-Linked Immunospot Assay
HIV
Cytotoxic T-Lymphocytes
Interferons
Antibody Formation
T-Lymphocytes
AIDS Vaccines
HIV Antibodies
Protein Subunits
Chromium
Neutralizing Antibodies
Immunoenzyme Techniques
HIV Infections
Healthy Volunteers
Placebos

Keywords

  • Canarypox vector
  • Cytotoxic T lymphocyte
  • Enzyme-linked immunospot assay
  • HIV vaccine
  • rgp120 subunit protein
  • vCP1452

ASJC Scopus subject areas

  • Virology
  • Immunology

Cite this

Phase 2 study of an HIV-1 canarypox vaccine (vCP1452) alone and in combination with rgp120 : Negative results fail to trigger a phase 3 correlates trial. / Russell, Nina D.; Graham, Barney S.; Keefer, Michael C.; McElrath, M. Juliana; Self, Steve G.; Weinhold, Kent J.; Montefiori, David C.; Ferrari, Guido; Horton, Helen; Tomaras, Georgia D.; Gurunathan, Sanjay; Baglyos, Lynn; Frey, Sharon E.; Mulligan, Mark J.; Harro, Clayton D.; Buchbinder, Susan P.; Baden, Lindsey R.; Blattner, William A.; Koblin, Beryl A.; Corey, Lawrence.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 44, No. 2, 02.2007, p. 203-212.

Research output: Contribution to journalArticle

Russell, ND, Graham, BS, Keefer, MC, McElrath, MJ, Self, SG, Weinhold, KJ, Montefiori, DC, Ferrari, G, Horton, H, Tomaras, GD, Gurunathan, S, Baglyos, L, Frey, SE, Mulligan, MJ, Harro, CD, Buchbinder, SP, Baden, LR, Blattner, WA, Koblin, BA & Corey, L 2007, 'Phase 2 study of an HIV-1 canarypox vaccine (vCP1452) alone and in combination with rgp120: Negative results fail to trigger a phase 3 correlates trial', Journal of Acquired Immune Deficiency Syndromes, vol. 44, no. 2, pp. 203-212. https://doi.org/10.1097/01.qai.0000248356.48501.ff
Russell, Nina D. ; Graham, Barney S. ; Keefer, Michael C. ; McElrath, M. Juliana ; Self, Steve G. ; Weinhold, Kent J. ; Montefiori, David C. ; Ferrari, Guido ; Horton, Helen ; Tomaras, Georgia D. ; Gurunathan, Sanjay ; Baglyos, Lynn ; Frey, Sharon E. ; Mulligan, Mark J. ; Harro, Clayton D. ; Buchbinder, Susan P. ; Baden, Lindsey R. ; Blattner, William A. ; Koblin, Beryl A. ; Corey, Lawrence. / Phase 2 study of an HIV-1 canarypox vaccine (vCP1452) alone and in combination with rgp120 : Negative results fail to trigger a phase 3 correlates trial. In: Journal of Acquired Immune Deficiency Syndromes. 2007 ; Vol. 44, No. 2. pp. 203-212.
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abstract = "BACKGROUND: A goal of T-cell HIV vaccines is to define the correlation between a vaccine-induced immune response and protection from HIV infection. We conducted a phase 2 trial to determine if a canarypox vaccine candidate (vCP1452) administered with rgp120 subunit protein would {"}qualify{"} for a trial to define a correlate of efficacy. METHODS: A total of 330 healthy volunteers were enrolled into 4 groups: 120 received vCP1452 alone (0, 1, 3, and 6 months), 120 received vCP1452 with 2 different regimens of rgp120 coadministration, and 90 received placebo. HIV-specific antibody responses were measured by enzyme-linked immunoassay (ELISA) and neutralizing activity. T-cell responses were measured by chromium release and interferon-γ (IFNγ) enzyme-linked immunospot (ELISpot) assay. RESULTS: Significant neutralizing antibody responses to the HIV MN strain were detected in all vaccine groups, with net responses ranging from 57{\%} (95{\%} confidence interval [CI]: 40{\%} to 71{\%}) to 94{\%} (95{\%} CI: 85{\%} to 99{\%}). Net cumulative HIV-specific CD8 IFNγ ELISpot assay responses were 13{\%} (95{\%} CI: -1{\%} to 26{\%}) for recipients of vCP1452 alone and 16{\%} (95{\%} CI: 2{\%} to 29{\%}) for recipients of vCP1452 plus rgp120. CONCLUSIONS: Overall, the HIV-specific CD8 cytotoxic T lymphocyte (CTL) response was not sufficient to qualify the regimen for a subsequent trial designed to detect an immune correlate of protection requiring a minimum CD8 CTL frequency of 30{\%}.",
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T1 - Phase 2 study of an HIV-1 canarypox vaccine (vCP1452) alone and in combination with rgp120

T2 - Negative results fail to trigger a phase 3 correlates trial

AU - Russell, Nina D.

AU - Graham, Barney S.

AU - Keefer, Michael C.

AU - McElrath, M. Juliana

AU - Self, Steve G.

AU - Weinhold, Kent J.

AU - Montefiori, David C.

AU - Ferrari, Guido

AU - Horton, Helen

AU - Tomaras, Georgia D.

AU - Gurunathan, Sanjay

AU - Baglyos, Lynn

AU - Frey, Sharon E.

AU - Mulligan, Mark J.

AU - Harro, Clayton D.

AU - Buchbinder, Susan P.

AU - Baden, Lindsey R.

AU - Blattner, William A.

AU - Koblin, Beryl A.

AU - Corey, Lawrence

PY - 2007/2

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N2 - BACKGROUND: A goal of T-cell HIV vaccines is to define the correlation between a vaccine-induced immune response and protection from HIV infection. We conducted a phase 2 trial to determine if a canarypox vaccine candidate (vCP1452) administered with rgp120 subunit protein would "qualify" for a trial to define a correlate of efficacy. METHODS: A total of 330 healthy volunteers were enrolled into 4 groups: 120 received vCP1452 alone (0, 1, 3, and 6 months), 120 received vCP1452 with 2 different regimens of rgp120 coadministration, and 90 received placebo. HIV-specific antibody responses were measured by enzyme-linked immunoassay (ELISA) and neutralizing activity. T-cell responses were measured by chromium release and interferon-γ (IFNγ) enzyme-linked immunospot (ELISpot) assay. RESULTS: Significant neutralizing antibody responses to the HIV MN strain were detected in all vaccine groups, with net responses ranging from 57% (95% confidence interval [CI]: 40% to 71%) to 94% (95% CI: 85% to 99%). Net cumulative HIV-specific CD8 IFNγ ELISpot assay responses were 13% (95% CI: -1% to 26%) for recipients of vCP1452 alone and 16% (95% CI: 2% to 29%) for recipients of vCP1452 plus rgp120. CONCLUSIONS: Overall, the HIV-specific CD8 cytotoxic T lymphocyte (CTL) response was not sufficient to qualify the regimen for a subsequent trial designed to detect an immune correlate of protection requiring a minimum CD8 CTL frequency of 30%.

AB - BACKGROUND: A goal of T-cell HIV vaccines is to define the correlation between a vaccine-induced immune response and protection from HIV infection. We conducted a phase 2 trial to determine if a canarypox vaccine candidate (vCP1452) administered with rgp120 subunit protein would "qualify" for a trial to define a correlate of efficacy. METHODS: A total of 330 healthy volunteers were enrolled into 4 groups: 120 received vCP1452 alone (0, 1, 3, and 6 months), 120 received vCP1452 with 2 different regimens of rgp120 coadministration, and 90 received placebo. HIV-specific antibody responses were measured by enzyme-linked immunoassay (ELISA) and neutralizing activity. T-cell responses were measured by chromium release and interferon-γ (IFNγ) enzyme-linked immunospot (ELISpot) assay. RESULTS: Significant neutralizing antibody responses to the HIV MN strain were detected in all vaccine groups, with net responses ranging from 57% (95% confidence interval [CI]: 40% to 71%) to 94% (95% CI: 85% to 99%). Net cumulative HIV-specific CD8 IFNγ ELISpot assay responses were 13% (95% CI: -1% to 26%) for recipients of vCP1452 alone and 16% (95% CI: 2% to 29%) for recipients of vCP1452 plus rgp120. CONCLUSIONS: Overall, the HIV-specific CD8 cytotoxic T lymphocyte (CTL) response was not sufficient to qualify the regimen for a subsequent trial designed to detect an immune correlate of protection requiring a minimum CD8 CTL frequency of 30%.

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KW - vCP1452

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