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

Emma J. Bowles, Torben Schiffner, Maxim Rosario, Gemma A. Needham, Meghna Ramaswamy, Joanna McGouran, Benedikt Kessler, Celia La Branche, Andrew J. McMichael, David Montefiori, Quentin J. Sattentau, Tomáš Hanke, Guillaume B E Stewart-Jones

Research output: Contribution to journalArticle

Abstract

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 crossneutralizing 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.

Original languageEnglish (US)
Article numbere114709
JournalPLoS One
Volume9
Issue number12
DOIs
StatePublished - Dec 9 2014
Externally publishedYes

Fingerprint

Human immunodeficiency virus 1
Macaca mulatta
Neutralizing Antibodies
neutralizing antibodies
Antibody Formation
Macaca
antigens
Pseudovirus
vaccines
HIV-1
neutralization
adjuvants
Vaccines
binding sites
monoclonal antibodies
AIDS Vaccines
viruses
antibodies
GP 140
gp140 envelope protein, Human immunodeficiency virus 1

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Comparison of neutralizing antibody responses elicited from highly diverse polyvalent heterotrimeric HIV-1 gp140 cocktail immunogens versus a monovalent counterpart in rhesus macaques. / Bowles, Emma J.; Schiffner, Torben; Rosario, Maxim; Needham, Gemma A.; Ramaswamy, Meghna; McGouran, Joanna; Kessler, Benedikt; La Branche, Celia; McMichael, Andrew J.; Montefiori, David; Sattentau, Quentin J.; Hanke, Tomáš; Stewart-Jones, Guillaume B E.

In: PLoS One, Vol. 9, No. 12, e114709, 09.12.2014.

Research output: Contribution to journalArticle

Bowles, EJ, Schiffner, T, Rosario, M, Needham, GA, Ramaswamy, M, McGouran, J, Kessler, B, La Branche, C, McMichael, AJ, Montefiori, D, Sattentau, QJ, Hanke, T & Stewart-Jones, GBE 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, vol. 9, no. 12, e114709. https://doi.org/10.1371/journal.pone.0114709
Bowles, Emma J. ; Schiffner, Torben ; Rosario, Maxim ; Needham, Gemma A. ; Ramaswamy, Meghna ; McGouran, Joanna ; Kessler, Benedikt ; La Branche, Celia ; McMichael, Andrew J. ; Montefiori, David ; Sattentau, Quentin J. ; Hanke, Tomáš ; Stewart-Jones, Guillaume B E. / Comparison of neutralizing antibody responses elicited from highly diverse polyvalent heterotrimeric HIV-1 gp140 cocktail immunogens versus a monovalent counterpart in rhesus macaques. In: PLoS One. 2014 ; Vol. 9, No. 12.
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