Scientific Publications by FDA Staff

Clin Vaccine Immunol 2015 Oct;22(10):1096-108

Correlates of vaccine-induced protection against TB immune revealed in comparative analyses of lymphocyte populations.

Kurtz SL, Elkins KL

A critical hindrance to the development of a novel vaccine against Mycobacterium tuberculosis (MTB) is a lack of understanding of protective correlates of immunity and of host factors involved in a successful adaptive immune response. Several published studies have used a murine-based in vitro model system to assess correlates of protection, though much is still to be learned from this approach. Here, using this co-culture system and a panel of whole cell vaccines of varying efficacy, we attempted a more comprehensive approach to understanding correlates of protection. We compared the gene and protein expression profiles of vaccine-generated immune peripheral blood lymphocytes (PBL) to the profiles found in immune splenocytes. PBL not only represent a clinically relevant cell population, but comparing expression in these populations gave insight into compartmentally specific mechanisms of protection. Additionally, we performed a direct comparison of the host response induced when immune cells were co-cultured with either the vaccine strain M. bovis BCG or virulent MTB. This comparison revealed host specific factors involved in protection against virulent MTB. Though we found scientific value in examining the differences between the various sample combinations, PBL or splenocytes and BCG or MTB, the most significant finding is a set of 13 core molecules induced in the most protective vaccines in all of the conditions tested. Further validation of this panel of mediators as a predictor of vaccine efficacy may promote vaccine development, and an understanding of how each promotes adaptive immunity will further our understanding of anti-mycobacterial responses.