Aagaard C, Hoang T, Dietrich J, Cardona PJ, Izzo A, Dolganov G, Schoolnik GK, Cassidy JP, Billeskov R, Andersen P. A multistage tuberculosis vaccine that confers efficient protection before and after exposure. Nat Med. 2011 Jan 23. [Epub ahead of print]
Claus Aagaard, et al., presented a series of experiments in mice to determine if protection from a vaccine could be conferred after exposure by combining antigens currently used in TB vaccine candidates and an antigen that has been shown to be persistent in later stages of infection. The vaccine tested was called H56 and contained three antigens: Ag85B and ESAT-6 (preventative antigens), and Rv2660c (late stage expression/persistance). The results showed that H56 performed especially well during the persistent phase of of the infection in mice which is 12 weeks onward. It was comparable to BCG and H1 (Ag85B and ESAT-6 fusion protein) vaccines during early infection, and significantly superior to BCG and H1 during late infection, 24 weeks and 12 weeks respectively. Some key points from the article include:
- R2660c was selected because it was expressed from early to late stage infection at similar levels and it is associated with major transcriptional response.
- R2660c is not protective on its own; but, it had a 5- to 10-fold amplification of immune response as part of the H56 vaccine.
- The H56 vaccine promoted high-quality T cell responses with CD4+ T cells that were almost exclusively polyfunctional.
- The late stage activity of the H56 vaccine was also evident during BCG boosting experiments.
- The researchers are pursuing the clinical development of H56
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