The kinetics of antigen availability following immunization impact follicular helper T cell priming, germinal center responses, and ultimate antibody production, but clinically-relevant methods to control the duration of antigen delivery to lymph nodes in subunit vaccines are lacking. We conjugated antigens derived from the gp140 HIV envelope trimer with a phosphoserine (pSer) peptide that binds tightly to the most common clinical adjuvant, aluminum hydroxide (Alhydrogel, or alum). Site specific modification of an engineered outer domain (eOD) gp120 or stabilized SOSIP trimer immunogen with varying numbers of pSer groups allowed the binding strength to alum to be tuned and alum-bound antigens were presented from alum particle surfaces with a defined orientation.  pSer-antigen conjugates in alum could be tuned to steadily release antigen from an injection site over multiple weeks in mice. This persistence led to improved lymph node uptake and colocalization of antigen with B cell follicles. Ultimately, a 20-fold increase in titer relative to the unmodified protein was observed four weeks after primary immunization with both pSer-eOD and pSer-SOSIP conjugates, and long-lived plasma cells in bone marrow were doubled by immunization with pSer-modified immunogens. Additionally, conjugation of pSer linkers to the base of SOSIP trimers minimized the formation of base-specific antibodies, suggesting that antigen arrives in lymph nodes still bound to alum particles. Overall, pSer-antigen conjugates elicited significant increases in antibody titers and altered specificity of the humoral response through controlling the display of antigen on the surface of alum.<br/>

Enhancing humoral immunity to subunit vaccines through engineered immunogen binding to aluminum hydroxide adjuvant

2019 Spring National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.