New Vaccine May Be More Effective against Tuberculosis

Microscope image of
red-stained TB bacteria.
Image by Dr. George P. Kubica, Centers for Disease Control and Prevention.

Scientists have developed a new tuberculosis vaccine that targets proteins from both early and later stages of the disease. The new vaccine, called H56, prevents TB in infected mice more effectively than the current vaccine. These findings offer hope for a better defense against the disease, which kills nearly 2 million people every year.

TB is a bacterial infection of the lungs caused by Mycobacterium tuberculosis. It is a leading cause of death among young adults worldwide. A vaccine called Bacille Calmette Guerin, or BCG, is currently used against TB. However, BCG is not completely effective, and can't prevent reactivation of latent TB in people who carry the bacterium but don't have disease symptoms.

Dr. Claus Aagaard and Dr. Peter Andersen at the Staten Serum Institut in Denmark, supported by an international team of collaborators, hypothesized that a vaccine targeting both the active and latent stages of TB might give better protection. They created a triple fusion protein called H56. It combines 2 proteins that the bacteria produces in the early stages of infection with another produced during later-stage infection. The study was funded by NIH's National Institute of Allergy and Infectious Diseases (NIAID) and the Bill and Melinda Gates Foundation.

To test H56, the team vaccinated mice with H56, BCG or each of the single proteins. They then infected the mice and looked at how many TB bacteria remained in the lungs after 6 weeks. The results appeared online on January 23, 2011, in Nature Medicine.

H56 and BCG both out-performed the single-protein vaccines in keeping bacteria levels low. After 24 weeks, though, H56-treated mice had fewer bacteria than those treated with BCG, suggesting that H56 could be more protective in the later stages of infection.

To see if this stronger protection was due to the addition of the late-stage protein, the researchers compared H56 with H1, a fusion vaccine that contains the 2 early-stage proteins but lacks the late-stage protein. While H56 and H1 both produced strong immune responses, H56 kept bacteria levels lower 24 weeks after infection. Furthermore, when H56 and H1 were used as boosters for mice vaccinated with BCG, H56-treated mice had much lower levels of bacteria in their lungs than either the H1-boosted mice or the mice that had been vaccinated with just BCG.

Finally, the researchers looked at whether H56 could protect against reactivation of latent infection. To do this, they infected mice and treated them with antibiotics. Then, 10 weeks after infection, they treated the mice with H56. Several months later, the vaccinated mice showed much stronger immune responses than the non-vaccinated mice. They also had lower levels of bacteria in their lungs.

"Nobody has been able so far to really come up with a combination that, when tested in animal models that already harbor the bacteria in a way that humans might, can prevent progression to active disease," says Dr. Christine Sizemore, chief of NIAID's Tuberculosis, Leprosy and Other Mycobacterial Diseases section.

The new vaccine is now entering clinical trials, where researchers will learn whether it offers similar protection against TB in humans.

Investigator affiliations: Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark; Unitat de Tuberculosi Experimental, Institut per a la Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Catalonia, Spain; Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO; Department of Microbiology and Immunology, Stanford University School of Medicine, CA; Veterinary Sciences Centre, School of Agriculture, Food Science and Veterinary Medicine, University College Dublin, Belfield, Dublin, Ireland.