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A trimeric, V2-deleted HIV-1 envelope glycoprotein vaccine elicits potent neutralizing antibodies but limited breadth of neutralization in human volunteers.

Publication ,  Journal Article
Spearman, P; Lally, MA; Elizaga, M; Montefiori, D; Tomaras, GD; McElrath, MJ; Hural, J; De Rosa, SC; Sato, A; Huang, Y; Frey, SE; Sato, P ...
Published in: J Infect Dis
April 15, 2011

BACKGROUND: A key missing element in the development of a successful human immunodeficiency virus (HIV) vaccine is an immunogen that can generate broadly cross-neutralizing antibodies against primary isolates of the virus. METHODS: This phase 1 clinical trial employed a DNA prime and subunit envelope protein boost in an attempt to generate cellular and humoral immune responses that might be desirable in a protective HIV vaccine. Priming was performed via intramuscular injection with gag and env DNA adsorbed to polylactide coglycolide microspheres, followed by boosting with a recombinant trimeric envelope (Env) glycoprotein delivered in MF59 adjuvant. RESULTS: The DNA prime and protein boost were generally safe and well-tolerated. Env-specific CD4(+) cellular responses were generated that were predominantly detected after Env protein boosting. Neutralizing antibody responses against the homologous SF162 viral isolate were remarkably strong and were present in the majority of vaccine recipients, including a strong response against CD4-induced epitopes on gp120. Despite the promising potency of this vaccine approach, neutralization breadth against heterologous tier 2 strains of HIV-1 was minimal. CONCLUSIONS: Potent neutralization against neutralization-sensitive strains of HIV is achievable in humans through a DNA prime, recombinant oligomeric Env protein boost regimen. Eliciting substantial breadth of neutralization remains an elusive goal. CLINICAL TRIALS REGISTRATION: NCT00073216.

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Published In

J Infect Dis

DOI

EISSN

1537-6613

Publication Date

April 15, 2011

Volume

203

Issue

8

Start / End Page

1165 / 1173

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Vaccines, Synthetic
  • Microbiology
  • Immunization, Secondary
  • Immunity, Cellular
  • Humans
  • HIV-1
  • HIV Infections
  • Epitope Mapping
  • DNA, Viral
 

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Spearman, P., Lally, M. A., Elizaga, M., Montefiori, D., Tomaras, G. D., McElrath, M. J., … HIV Vaccine Trials Network of NIAID. (2011). A trimeric, V2-deleted HIV-1 envelope glycoprotein vaccine elicits potent neutralizing antibodies but limited breadth of neutralization in human volunteers. J Infect Dis, 203(8), 1165–1173. https://doi.org/10.1093/infdis/jiq175
Spearman, Paul, Michelle A. Lally, Marnie Elizaga, David Montefiori, Georgia D. Tomaras, M Juliana McElrath, John Hural, et al. “A trimeric, V2-deleted HIV-1 envelope glycoprotein vaccine elicits potent neutralizing antibodies but limited breadth of neutralization in human volunteers.J Infect Dis 203, no. 8 (April 15, 2011): 1165–73. https://doi.org/10.1093/infdis/jiq175.
Spearman P, Lally MA, Elizaga M, Montefiori D, Tomaras GD, McElrath MJ, et al. A trimeric, V2-deleted HIV-1 envelope glycoprotein vaccine elicits potent neutralizing antibodies but limited breadth of neutralization in human volunteers. J Infect Dis. 2011 Apr 15;203(8):1165–73.
Spearman, Paul, et al. “A trimeric, V2-deleted HIV-1 envelope glycoprotein vaccine elicits potent neutralizing antibodies but limited breadth of neutralization in human volunteers.J Infect Dis, vol. 203, no. 8, Apr. 2011, pp. 1165–73. Pubmed, doi:10.1093/infdis/jiq175.
Spearman P, Lally MA, Elizaga M, Montefiori D, Tomaras GD, McElrath MJ, Hural J, De Rosa SC, Sato A, Huang Y, Frey SE, Sato P, Donnelly J, Barnett S, Corey LJ, HIV Vaccine Trials Network of NIAID. A trimeric, V2-deleted HIV-1 envelope glycoprotein vaccine elicits potent neutralizing antibodies but limited breadth of neutralization in human volunteers. J Infect Dis. 2011 Apr 15;203(8):1165–1173.
Journal cover image

Published In

J Infect Dis

DOI

EISSN

1537-6613

Publication Date

April 15, 2011

Volume

203

Issue

8

Start / End Page

1165 / 1173

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Vaccines, Synthetic
  • Microbiology
  • Immunization, Secondary
  • Immunity, Cellular
  • Humans
  • HIV-1
  • HIV Infections
  • Epitope Mapping
  • DNA, Viral