T cell correlates of solid protective immunity following immunization of macaques with a live-attenuated trachoma vaccine (P4403)

Abstract

Abstract Trachoma, caused by Chlamydia trachomatis, is the world’s leading cause of preventable blindness for which a vaccine is needed. We previously described a live-attenuated trachoma vaccine (LATV) in non-human primates (Kari L. 2011 JEM 208: 2217-23). Vaccinated macaques were either solidly or partially protected following challenge with virulent trachoma organisms. Our current goal was to characterize immune responses that correlated with solid protective immunity. Here, we preformed intramuscular boosting of LATV vaccinated macaques and studied the T cell recall response in PBMC by flow cytometry. Both solidly and partially protected macaques exhibited a strong PBMC CD8+ T recall response following intramuscular immunization. Notably, however; only CD8+ T cells from solidly protected macaques strongly proliferated in response to chlamydial soluble antigen (SA) prepared from chlamydial infected cells. The SA contained proteins known to be secreted by chlamydiae into the host cytosol making them logical antigenic targets of cytotoxic CD8+ T cells. The SA expanded CD8+ T cells expressed IFN-γ, granzyme B, and α4β7 integrin implicating them as effectors important to the development of solid protective immunity at the ocular mucosae. Identifying the effector function and antigens recognized by these CD8+ T cells will be the focus of future studies as this information will provide insights into the design of more conventional immunotherapeutic approaches for trachoma control.