A multistage tuberculosis vaccine that confers efficient protection before and after exposure

Abstract

All tuberculosis vaccines currently in clinical trials are designed as prophylactic vaccines based on early expressed antigens. We have developed a multistage vaccination strategy in which the early antigens Ag85B and 6-kDa early secretory antigenic target (ESAT-6) are combined with the latency-associated protein Rv2660c (H56 vaccine). In CB6F1 mice we show that Rv2660c is stably expressed in late stages of infection despite an overall reduced transcription. The H56 vaccine promotes a T cell response against all protein components that is characterized by a high proportion of polyfunctional CD4(+) T cells. In three different pre-exposure mouse models, H56 confers protective immunity characterized by a more efficient containment of late-stage infection than the Ag85B-ESAT6 vaccine (H1) and BCG. In two mouse models of latent tuberculosis, we show that H56 vaccination after exposure is able to control reactivation and significantly lower the bacterial load compared to adjuvant control mice.

Vaccine against tuberculosis: what’s new?

“…In mouse models, H56 elicited a strong multifunctional CD4 + T-cells response and limited reactivation of latent TB [63]. …”

Multivalent TB vaccines targeting the esx gene family generate potent and broad cell-mediated immune responses superior to BCG

“…Vaccination with multiple immunodominant antigens from Mtb may be important to drive broad repertoire coverage to improve the protective effect of any new vaccination. 8,9 The most prominent antigens described for induction of cellmediated immunity have been members of the esx family. [10][11][12][13] The esx family consists of 23 members that are approximately 100 amino acids in length, with 13 members that can be further divided into 3 distinct subfamilies based on high sequence homology between the members.…”

Mtb32 is a promising tuberculosis antigen for DNA vaccination in pre- and post-exposure mouse models

“…Rv2660c, a latency-associated protein, has recently been identified as an effective post-exposure vaccine. 31 Nevertheless, the high abundance of antigen is not always correlated with the level protective efficacy. For example, while the expression of ESAT-6 is ten times higher than that of Ag85 complexes in the lungs of mouse, studies have shown that the bacterial burdens in the lungs are similarly reduced between mice immunized with ESAT-6 and Ag85B.…”