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Improvement of antibody responses by HIV envelope DNA and protein co-immunization

Pissani, F and Malherbe, DC and Schuman, JT and Robins, H and Park, BS and Krebs, SJ and Barnett, SW and Haigwood, NL (2014) Improvement of antibody responses by HIV envelope DNA and protein co-immunization. VACCINE. pp. 507-513.

Abstract

Background: Developing HIV envelope (Env) vaccine components that elicit durable and protective antibody responses is an urgent priority, given the results from the RV144 trial. Optimization of both the immunogens and vaccination strategies will be needed to generate potent, durable antibodies. Due to the diversity of HIV, an effective Env-based vaccine will most likely require an extensive coverage of antigenic variants. A vaccine co-delivering Env immunogens as DNA and protein components could provide such coverage. Here, we examine a DNA and protein co-immunization strategy by characterizing the antibody responses and evaluating the relative contribution of each vaccine component.Method: We co-immunized rabbits with representative subtype A or B HIV gp160 plasmid DNA plus Env gp140 trimeric glycoprotein and compared the responses to those obtained with either glycoprotein alone or glycoprotein in combination with empty vector.Results: DNA and glycoprotein co-immunization was superior to immunization with glycoprotein alone by enhancing antibody kinetics, magnitude, avidity, and neutralizing potency. Importantly, the empty DNA vector did not contribute to these responses. Humoral responses elicited by mismatched DNA and protein components were comparable or higher than the responses produced by the matched vaccines.Conclusion: Our data show that co-delivering DNA and protein can augment antibodies to Env. The rate and magnitude of immune responses suggest that this approach has the potential to streamline vaccine regimens by inducing higher antibody responses using fewer vaccinations, an advantage for a successful HIV vaccine design. (C) 2013 Elsevier Ltd. All rights reserved

Item Type: Article
Additional Information: NIBR author: Barnett, S institute: NIBR contributor address: Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97217 USA, Vaccine & Gene Therapy Inst, Beaverton, OR 97006 USA, Oregon Natl Primate Res Ctr, Beaverton, OR 97006 USA haigwoon@ohsu.edu; Oregon Natl Primate Res Ctr, Beaverton, OR 97006 USA ; GE Healthcare, Piscataway, NJ 08854 USA ; Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA ; Oregon Natl Primate Res Ctr, Beaverton, OR 97006 USA, Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA ; Vaccine & Gene Therapy Inst, Beaverton, OR 97006 USA, Oregon Natl Primate Res Ctr, Beaverton, OR 97006 USA ; Novartis Inst Biomed Res, Cambridge, MA 02139 USA ; Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97217 USA; Vaccine & Gene Therapy Inst, Beaverton, OR 97006 USA; Oregon Natl Primate Res Ctr, Beaverton, OR 97006 USA; Haigwood, N L; Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, 505 NW 185th Ave, Beaverton, OR 97006 USA
Date Deposited: 13 Oct 2015 13:12
Last Modified: 13 Oct 2015 13:12
URI: https://oak.novartis.com/id/eprint/22634

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