Post-translational modification for HIV-1 vaccine design
International Joint Usage/Research Center Seminar
"Post-translational modification for HIV-1 vaccine design"
Seminar Date and Time: 02/05/2020 (Wed) 14:00 ~ 15:00
Venue: 1st Central Building 2F, 2-1 Seminar Room
Speaker (Name): Quentin Sattentau
Affiliation, Title: Sir William Dunn School of Pathology, University of Oxford, UK. /Professor
Subject: Post-translational modification for HIV-1 vaccine design
Abstract: An effective vaccine to reduce or prevent the spread of HIV-1 is an urgent global health priority. Neutralizing antibodies block transmission of retroviruses between hosts, but we have yet to elicit them by active vaccination. The target of neutralizing antibodies is the viral envelope glycoproteins (Env), and broadly neutralizing antibodies (bnAbs) have been isolated from infected individuals and their highly conserved epitopes mapped. However, Env has evolved immune evasion mechanisms that pose substantial challenges to vaccine design, including high rates of antigenic variation, extensive glycosylation, and conformational instability. We have addressed Env conformational instability by use of chemical cross-linking approaches followed by selection of specific conformational forms. Cross-linking enhanced Env stability whilst conserving overall Env structure and preserving bnAb epitopes. Immunization of small animals with cross-linked Env resulted in enhanced neutralizing antibody titers and breadth, and this approach is currently being tested in an experimental medicine clinical vaccine trial. A second challenge is the glycan shield that protects the Env protein surface from B cell recognition. We are exploring approaches to induce neutralizing antibodies to Env glycans by chemical adduction of semi-synthetic glycans in a manner that enhances glycan immunogenicity. These general approaches may assist in the design of vaccines against other microbial pathogens and cancer.
Organizer (Host Researcher): Professor Ken Ishii