A different delivery route may improve tuberculosis vaccine effectiveness

2020

Challenge

Tuberculosis (TB) is the world’s leading cause of death from infection. The only licensed TB vaccine, known as the Bacille Calmette-Guerin (BCG) vaccine, was developed a century ago. This vaccine works well when given to infants through an injection just under the skin. However, in adults, this type of delivery is far less effective at preventing TB from infecting the lungs, which is the main cause of TB-related illness and death in teens and adults. To control TB infection and prevent symptomatic disease, a vaccine must elicit strong, sustained responses from the immune system’s infection-fighting T cells, but the traditional approach of delivering the BCG vaccine into the skin may not generate enough of these critical cells in the lungs to immediately control TB infection in that part of the body.

Advance

To determine if a different dose or route of administration of the BCG vaccine could be more effective at preventing TB infection in the lungs, IRP researchers led by senior investigators Robert A. Seder, M.D., and Mario Roederer, Ph.D., carried out a study in rhesus monkeys. They found that intravenous administration of the BCG vaccine — injection into a vein rather than beneath the skin — significantly increased immune responses in the blood and lungs and prevented infection and disease in the majority of animals compared to vaccination with the same dose given via skin injection or aerosol nasal spray.

Impact

Despite widespread vaccination, TB was responsible for 1.5 million deaths and 10 million illnesses worldwide in 2018. This study provides a new framework to understand how TB vaccine delivery can provide protection against TB and should guide the field of TB vaccine research.

Publications

Darrah PA, Zeppa JJ, Maiello P, Hackney JA, Wadsworth MH 2nd, Hughes TK, Pokkali S, Swanson PA 2nd, Grant NL, Rodgers MA, Kamath M, Causgrove CM, Laddy DJ, Bonavia A, Casimiro D, Lin PL, Klein E, White AG, Scanga CA, Shalek AK, Roederer M, Flynn JL, Seder RA. (2020). Prevention of tuberculosis in macaques after intravenous BCG immunization. Nature. Jan;577(7788):95-102. doi: 10.1038/s41586-019-1817-8.