Efficient protection against Mycobacterium tuberculosis by vaccination with a single subdominant epitope from the ESAT-6 antigen

Abstract

We have investigated the vaccine potential of two peptides derived from the 6‐kDa early secretory antigenic target (ESAT)‐6 antigen in the mouse model of tuberculosis. The peptides were both strongly immunogenic in B6CBAF1 (H‐2b,k) mice and primed recall responses of the same intensity after immunization. However, both tuberculosis infection and immunization with ESAT‐6 resulted in responses focused towards ESAT‐61 – 20. Multiple antigen peptide constructs as well as free peptides were emulsified with dimethyl dioctadecylammonium bromide / monophosphoryl lipid A / IL‐2 and tested as experimental vaccines in an i. v. and aerosol model of tuberculosis in mice. The peptide were highly immunogenic and induced cellular responses of the same magnitude. However, only vaccines based on the subdominant ESAT‐651 – 70 epitope promoted significant levels of protective immunity and the level of protection was equivalent to that achieved with ESAT‐6 and BCG. These findings demonstrate the potential of peptide‐based vaccines against tuberculosis and indicate that there is not direct correlation between the hierarchy of response to naturally processed peptides and their ability to induce protective immunity against Mycobacterium tuberculosis.

Adenovirally-Induced Polyfunctional T Cells Do Not Necessarily Recognize the Infected Target: Lessons from a Phase I Trial of the AERAS-402 Vaccine

“…Additionally, a limitation of this study is that sub dominant or “cryptic” epitopes might nonetheless be augmented and hence protective following natural infection with Mtb, as shown in the murine model404142. In the approach taken in this report, we have likely failed to map those sub dominant epitopes.…”

A Small Protein but with Diverse Roles: A Review of EsxA in Mycobacterium–Host Interaction

“…Combined with proper adjuvants, EsxA induces both strong Th1 and humoral responses and provides comparable protection as the BCG vaccine in animal models [37]. The epitope EsxA 51-70 induces effective protection against Mtb challenge [179]. When combined with Ag85b, another Mtb immunodominant antigen [180], EsxA vaccination induces even a longer protection effect in mouse lung than BCG (30).…”

Mycobacterium tuberculosis Rv0679c protein sequences involved in host-cell infection: Potential TB vaccine candidate antigen

“…Synthetic peptides have been also used with success for screening pathogen-specific genome regions of putative protective importance in order to identify T-cell reactivity [12]. In TB, synthetic peptides have shown good results for diagnosing TB in cattle [13] and in a protective vaccine tested in mice [14]. …”