Induction of HIV Neutralizing Antibodies against the MPER of the HIV Envelope Protein by HA/gp41 Chimeric Protein-Based DNA and VLP Vaccines

• DOI: 10.1371/journal.pone.0014813
• Publication Date: 2011-05-19T20:57:54Z
• Authors: Ling Ye; Zhiyuan Wen; Ke Dong; Xi Wang; Zhigao Bu; Huizhong Zhang; Richard W. Compans; Chinglai Yang
• Keywords: Enfuvirtide

Several conserved neutralizing epitopes have been identified in the HIV Env protein and among these, MPER of gp41 has received great attention is widely recognized as a promising target. However, little success achieved eliciting MPER-specific antibodies by number different vaccine strategies. We investigated ability HA/gp41 chimeric protein-based vaccines, which were designed to enhance exposure its native conformation, induce antibodies. In characterization protein, we found that mutating an unpaired Cys residue (Cys-14) HA1 subunit Ser residue, modified HA-C14S/gp41 showed increased reactivity conformation-sensitive monoclonal antibody against HA formed more stable trimers VLPs. On other hand, proteins expressed on cell surfaces exhibited similar 2F5 4E10. Immunization guinea pigs using DNA or VLP vaccines induced well peptide corresponding segment at higher levels than immunization standard Further, sera from vaccinated exhibit activities. Moreover, but not VLPs, neutralize pseudovirions containing SIV-4E10 protein. The virus neutralization could be blocked peptide, thus demonstrating induction this novel strategy. These results show can through rationally