Induction of Antibodies Specific for Gp41 of HIV-1 by Gene Gun DNA Vaccination
Rayk Behrendt, Uwe Fiebig, Mirco Schmolke, Reinhard Kurth and Joachim Denner*
Robert Koch Institute, Berlin, Germany
- *Corresponding Author:
- Dr. Joachim Denner
Robert Koch Institute, Nordufer 20, D-13353 Berlin, Germany
Tel: +49 30 18745 2800
Fax: +49 30 18745 2801
E-mail: [email protected]
Received date: June 18, 2012; Accepted date: August 16, 2012; Published date: August 22, 2012
Citation: Behrendt R, Fiebig U, Schmolke M, Kurth R, Denner J (2012) Induction of Antibodies Specific for Gp41 of HIV-1 by Gene Gun DNA Vaccination. J Vaccines Vaccin 3:145. doi:10.4172/2157-7560.1000145
Copyright: © 2012 Behrendt R, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
All attempts to induce broadly neutralising antibodies such as mAb 2F5 and mAb 4E10 targeting conserved epitopes in the membrane proximal external region (MPER) of the transmembrane envelope (TM) protein gp41 of HIV-1 failed so far. In contrast, in previous studies, immunising with the ectodomain of the TM protein p15E of different gammaretroviruses, we successfully induced neutralising antibodies. These antibodies recognised epitopes located in the fusion peptide proximal region (FPPR) and in the MPER of p15E. The epitope in the MPER of p15E corresponds to that of the mAb 4E10 in gp41 in terms of location within the protein and partial sequence homology. In order to present the MPER of gp41 (containing the 2F5 and 4E10 epitopes) membrane-associated, rats were immunised with DNA constructs corresponding (i) to the entire gp41, (ii) to the C-terminal helix of gp41 and (iii) to hybrid proteins composed of a backbone derived from p15E of a gammaretrovirus with inserted FPPR and MPER from gp41 of HIV-1. After transfection in vitro these proteins were found expressed at the cell surface and the accessibility of the 2F5 epitope was demonstrated by flow cytometry. However, DNA vaccination in rats resulted only in low titres of antibodies specific for the MPER of HIV-1, and none of the sera was neutralising.