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Comparison of neutralizing antibody responses elicited from highly diverse polyvalent heterotrimeric HIV-1 gp140 cocktail immunogens versus a monovalent counterpart in rhesus macaques.

Publication ,  Journal Article
Bowles, EJ; Schiffner, T; Rosario, M; Needham, GA; Ramaswamy, M; McGouran, J; Kessler, B; LaBranche, C; McMichael, AJ; Montefiori, D; Hanke, T ...
Published in: PLoS One
2014

Eliciting neutralizing antibodies capable of inactivating a broad spectrum of HIV-1 strains is a major goal of HIV-1 vaccine design. The challenge is that envelopes (Envs) of circulating viruses are almost certainly different from any Env used in a vaccine. A novel immunogen composed of a highly diverse set of gp140 Envs including subtypes A, B, C, D and F was developed to stimulate a more cross-neutralizing antibody response. Env heterotrimers composed of up to 54 different gp140s were produced with the aim of focusing the response to the conserved regions of Env while reducing the dominance of any individual hypervariable region. Heterotrimeric gp140 Envs of inter- and intra-subtype combinations were shown to bind CD4 and a panel of neutralizing monoclonal antibodies with similar affinity to monovalent UG37 gp140. Macaques immunized with six groups of heterotrimer mixtures showed slightly more potent neutralizing antibody responses in TZM-BL tier 1 and A3R5 tier 2 pseudovirus assays than macaques immunized with monovalent Env gp140, and exhibited a marginally greater focus on the CD4-binding site. Carbopol enhanced neutralization when used as an adjuvant instead of RIBI in combination with UG37 gp140. These data indicate that cross-subtype heterotrimeric gp140 Envs may elicit some improvement of the neutralizing antibody response in macaques compared to monovalent gp140 Env.

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2014

Volume

9

Issue

12

Start / End Page

e114709

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Neutralization Tests
  • Macaca mulatta
  • HIV-1
  • General Science & Technology
  • Antibody Formation
  • Antibodies, Neutralizing
  • Animals
  • AIDS Vaccines
 

Citation

APA
Chicago
ICMJE
MLA
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Bowles, E. J., Schiffner, T., Rosario, M., Needham, G. A., Ramaswamy, M., McGouran, J., … Stewart-Jones, G. B. E. (2014). Comparison of neutralizing antibody responses elicited from highly diverse polyvalent heterotrimeric HIV-1 gp140 cocktail immunogens versus a monovalent counterpart in rhesus macaques. PLoS One, 9(12), e114709. https://doi.org/10.1371/journal.pone.0114709
Bowles, Emma J., Torben Schiffner, Maximillian Rosario, Gemma A. Needham, Meghna Ramaswamy, Joanna McGouran, Benedikt Kessler, et al. “Comparison of neutralizing antibody responses elicited from highly diverse polyvalent heterotrimeric HIV-1 gp140 cocktail immunogens versus a monovalent counterpart in rhesus macaques.PLoS One 9, no. 12 (2014): e114709. https://doi.org/10.1371/journal.pone.0114709.
Bowles EJ, Schiffner T, Rosario M, Needham GA, Ramaswamy M, McGouran J, Kessler B, LaBranche C, McMichael AJ, Montefiori D, Sattentau QJ, Hanke T, Stewart-Jones GBE. Comparison of neutralizing antibody responses elicited from highly diverse polyvalent heterotrimeric HIV-1 gp140 cocktail immunogens versus a monovalent counterpart in rhesus macaques. PLoS One. 2014;9(12):e114709.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2014

Volume

9

Issue

12

Start / End Page

e114709

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Neutralization Tests
  • Macaca mulatta
  • HIV-1
  • General Science & Technology
  • Antibody Formation
  • Antibodies, Neutralizing
  • Animals
  • AIDS Vaccines