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Effective, low-titer antibody protection against low-dose repeated mucosal SHIV challenge in macaques


Neutralizing antibodies are thought to be crucial for HIV vaccine protection, but studies in animal models suggest that high antibody concentrations are required1. This is a major potential hurdle for vaccine design. However, these studies typically apply a large virus inoculum to ensure infection in control animals in single-challenge experiments. In contrast, most human infection via sexual encounter probably involves repeated exposures to much lower doses of virus2,3,4. Therefore, animal studies may have provided an overestimate of the levels of antibodies required for protection in humans. We investigated whether plasma concentrations of antibody corresponding to relatively modest neutralization titers in vitro could protect macaques from repeated intravaginal exposure to low doses of a simian immunodeficiency virus–HIV chimera (SHIV) that uses the CC chemokine receptor 5 (CCR5) co-receptor. An effector function–deficient variant of the neutralizing antibody was also included. The results show that a substantially larger number of challenges is required to infect macaques treated with neutralizing antibody than control antibody–treated macaques, and support the notion that effector function may contribute to antibody protection. Overall, the results imply that lower amounts of antibody than previously considered protective may provide benefit in the context of typical human exposure to HIV-1.

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Figure 1: Viral loads in antibody-treated macaques during vaginal low-dose repeated challenge with SHIVSF162P3.
Figure 2: Kaplan-Meier analysis and magnitude of protection by b12 and LALA treatment in low-dose (10TCID50) repeated challenge.


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ELISA for recombinant monomeric HIV-1 gp120JR-FL was provided by Progenics. We thank K. Saye-Francisco for antibody production and quality control assistance at The Scripps Research Institute and S. Hoffenberg at the IAVI AIDS Vaccine Design Laboratory. We thank A. Haahr Andreasen for statistical advice and analysis. We are grateful for the assistance provided by E. Rakasz, G. Borchardt, and C. McNair with genotyping and viral load assessments at the Wisconsin National Primate Research Center. We also thank M. Huber and R. Astronomo for reviewing the manuscript. Support for this work was provided by US National Institutes of Health (NIH) grant AI55332 to D.R.B., by the Neutralizing Antibody Consortium of the International AIDS Vaccine Initiative and by the Swiss National Foundation, Fellowship PA00A-109033.

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Project planning was performed by A.J.H., L.H., P.A.M. and D.R.B.; experimental work was done by A.J.H., L.H., M.H. and D.M.T.; data analysis was done by A.J.H., L.H., P.P., W.K.B., P.W.H.I.P. and D.R.B.; and A.J.H., P.P., P.W.H.I.P. and D.R.B. composed the manuscript.

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Competing interests

D.R.B. is listed as an inventor on patents describing the human neutralizing antibody b12. These patents include Australia Patent No. 681360, Patent Co-operation Treaty (PCT) Patent No. WO 94/07922, US Patent No. 5,652,138, Australia Patent No. 706601, US Patent No. 5,804,440 and PCT Patent No. WO 96/02273. Patents with the patent offices of Canada, the EU, Finland, Japan and Norway are pending. D.R.B. is also listed on patents describing the synthetic human neutralizing antibody, including the continuation-in-part PCT Patent No. 95/11317 and patents pending in the patent offices of Canada, the EU and Japan.

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Hessell, A., Poignard, P., Hunter, M. et al. Effective, low-titer antibody protection against low-dose repeated mucosal SHIV challenge in macaques. Nat Med 15, 951–954 (2009).

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