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This article is part of the supplement: AIDS Vaccine 2012

Open Access Poster presentation

Rapid development of cross-clade neutralizing antibody responses after clade B gp120/gp140 protein priming and clade c gp140 protein boosting

P Spearman1*, G Tomaras2, D Montefiori2, Y Huang3, H Ahmed3, M Elizaga3, J Hural3, J McElrath3, L Ouedraogo4, M Pensiero4, C Butler4, S Kalams5, ET Overton6, S Barnett7 and N Group1

  • * Corresponding author: P Spearman

Author Affiliations

1 Emory University, Atlanta, GA, USA

2 Department of Surgery, Duke Human Vaccine Institute, Durham, NC, USA

3 Fred Hutchinson Cancer Research Center, Seattle, WA, USA

4 Division of AIDS, NIAID, NIH, Bethesda, MD, USA

5 Vanderbilt University School of Medicine, Nashville, TN, USA

6 University of Alabama at Birmingham, Birmingham, AL, USA

7 Novartis Vaccines and Diagnostics, Cambridge, MA, USA

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Retrovirology 2012, 9(Suppl 2):P137  doi:10.1186/1742-4690-9-S2-P137

The electronic version of this article is the complete one and can be found online at: http://www.retrovirology.com/content/9/S2/P137


Published:13 September 2012

© 2012 Spearman et al; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background

Immunization with heterologous Env protein immunogens following an immunologic rest period has the potential to generate cross-clade neutralizing antibody responses. We identified individuals who had received a clade B Env protein with MF59 4-17 years earlier, most in combination with a DNA or ALVAC prime, and administered a clade C protein boost in an open label phase 1 trial.

Methods

Sixteen previously primed volunteers and 20 naïve volunteers each received 2 doses of a clade C TV1 trimeric Env protein with MF59 given 6 months apart. HIV-1 specific CD4+ and CD8+ T cell responses were measured by an intracellular cytokine staining (ICS) assay. Antibody responses were measured with a Luminex binding antibody assay and a neutralizing antibody assay in TZM-bl Cells.

Results

Despite the long interval, 31% of primed participants demonstrated CD4+ T cell responses to Env at baseline, which increased to 75% after a single protein boost. IgG and IgA responses to TV1 trimeric Env were present in 64% (IgG) and 7% (IgA) of primed participants at baseline, and rose to 93% and 85%, respectively, after one dose of protein. 71% of primed participants demonstrated neutralizing antibodies against Tier 1 clade B isolate MN at baseline. After a single booster dose of protein, 100% of the primed participants neutralized MN and 93% showed neutralizing activity against a clade C isolate, MW965.26. Unprimed participants did not demonstrate CD4+ responses or antibody responses to Env until after the second dose, which elicited IgG and IgA responses to TV1 trimeric Env in 88% and 50%, respectively. Neutralizing antibody developed to MN in 38% and to MW965.26 in 88% of the unprimed participants.

Conclusion

These results demonstrate the durability of vaccine-elicited HIV-1 specific antibody responses and support current efforts to enhance the breadth and magnitude of neutralizing antibodies through heterologous protein prime-boost regimens.