In a new paper published yesterday by Nature Medicine, researchers from the Statens Serum Institut (SSI) in Denmark describe encouraging results obtained with a new TB vaccine candidate. The design of the vaccine was informed by data showing that a particular TB protein, Rv2660c, remains strongly expressed during latent infection. This knowledge prompted the development of a “multistage” vaccine including Rv2660c along with two other TB antigens, Ag85B and ESAT-6. The resulting fusion protein vaccine is named H56. The goal is to create a vaccine capable of preventing active TB regardless of whether it is given before or after exposure.
In a mouse model of TB infection, the H56 vaccine was shown to be significantly superior in reducing bacterial load when compared to both the standard BCG vaccine and another candidate, H1, which contains only Ag85B and ESAT-6 antigens. The differences in efficacy took some time to become evident: 12 weeks after challenge in comparison to H1, and 24 weeks in comparison to BCG. Immune responses to the Rv2660c protein were weak early on but grew in magnitude over the period of follow up. In an experiment designed to evaluate the potential for post-exposure protection, H56 was found to provide a significant degree of protection against TB reactivation.
Based on these results, SSI is now initiating clinical development of H56. The current status of new TB vaccine candidates in clinical trials, including SSI’s, is summarized in a recent report from the 2010 Global TB Vaccines Forum on TAG’s website.
Nature Medicine (2011) doi:10.1038/nm.2285
Received 12 October 2010 Accepted 07 December 2010 Published online 23 January 2011
Claus Aagaard, Truc Hoang, Jes Dietrich, Pere-Joan Cardona, Angelo Izzo, Gregory Dolganov, Gary K Schoolnik, Joseph P Cassidy, Rolf Billeskov & Peter Andersen
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.