- Poster presentation
- Open Access
Assessing the protective efficacy of antibodies to the HIV gp41 region by active vaccination
© Sharma et al; licensee BioMed Central Ltd. 2012
- Published: 13 September 2012
- Protective Efficacy
- Envelope Glycoprotein
- Bacteriophage Particle
- Passive Immunization
- Protective Capacity
The gp41 cluster I is a conserved immunodominant loop connecting the heptad repeat 1 (HR 1) and heptad repeat 2 (HR2) of the HIV-1 the envelope glycoproteins (Env). Following HIV-1 infection or vaccination with gp41-containing Env immunogens, this region elicits relatively high titers of antibodies generally considered to be non-neutralizing in nature. However, in a recent passive immunization study using a cluster 1 antibody, partial protection against SHIV SF162 P4 challenge was observed. In the present study, we sought to determine if vaccine-elicited cluster 1 antibodies might afford some protective capacity by active vaccination, presumably by binding to non-functional spikes on the virus and slowing the viral entry process in vivo.
To generate cluster 1-specific antibodies, we added residues flanking the cluster I cysteine-loop region to allow it to assume its preferred structural conformation. The resultant 20 residues peptides were expressed on the genetically modified Q-beta bacteriophage particles and also chemically coupled to KLH. Sera from rabbits immunized with these antigens were analyzed by ELISA for the binding to cluster 1 peptides and by cross-competition with the known cluster I antibodies.
The cluster I region was found to be immunogenic and, interestingly, a version of the epitope in which alanines were substituted in place of the small cysteine-linked loop was found to be more immunogenic than the wild-type cysteine-cysteine motif. The sera from rabbits inoculated with either carrier cross-competed with the known cluster I antibodies such as F240. Though the sera did not neutralize JR-FL viruses, they serum antibodies were able to capture many different viruses in vitro.
We conclude that we have specifically elicited antibodies directed to the cluster 1 region of gp41 possessing properties similar to the known monoclonal antibodies. Active immunization of non-human primates by both the intranasal and intramuscular routes, followed by SHIV.
This article is published under license to 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.