The long-term objective is the development of fully synthetic immunogens, suitable for elicitation of long-term protective immunity in humans against human T-lymphotrophic virus type III (HTLV-III) [=lymphadenopathy-associated virus (LAV) or AIDS-associated retrovirus (ARV); abbreviated in the following text as HTLV-3], and resulting in prevention of the acquired immune deficiency syndrome (AIDS), and probably of other diseases associated with HTLV-3 infections, for example Kaposi sarcoma, lymphomas, etc. Peptides corresponding to segments of the amino acid sequence deduced from the nucleotide sequence of the HTLV-3 (clone BH10) envelope (env) protein will be synthesized and used to immunize experimental animals. The resulting antisera will be tested for antibodies (a) reacting with the homologous peptides, (b) reacting with HTLV-3 env proteins and (c) neutralizing the infectivity of the HTLV-3-BH10. The reactivity of antibodies from human sera (positive for anti-HTLV-3 and containing antibodies neutralizing the infectivity of HTLV-3 [VN-Ab] with the synthetic peptides will be tested. The ability of synthetic peptides to react with VN-Ab will be assessed in immunochromatography experiments. Peptides reacting with human VN-Ab and eliciting VN-Ab in experimental animals will be selected for more detailed studies. The sequence variability between HTLV-3 env protein regions, corresponding to distinct HTLV-3 isolates, demarcated by the selected peptide(s) will be assessed from available sequencing data. If warranted by sequence variability, additional peptides [differing in sequence but not in position along the env protein] will be synthesized. The immunological cross-reactivity between the peptides and their ability to induce VN-Ab against distinct HTLV-3 isolates will be determined. The possibility of shifts in the localization of VN epitopes along the env sequences of distinct viral isolates will also be considered. The proposed experiments are expected to result in identification of a few related synthetic analogs, which can be synthesized simultaneously and form the basis of a """"""""multivalent"""""""" vaccine eliciting broad protection against HTLV-3 """"""""subtypes"""""""".
Showing the most recent 10 out of 20 publications
