- Genetically engineered for attenuated virulence
- Better than naturally-occurring bacteria at inducing host immune responses
- Ideal for vaccine formulation
Together with colleagues at another institution, researchers at The University of North Carolina at Chapel Hill (UNC) have generated genetically engineered mycobacteria that can be used to develop mycobacteria vaccines. Making an effective vaccine against Mycobacterium tuberculosis (M. tuberculosis), the bacteria that cause tuberculosis, is difficult because the naturally-occurring bacteria have strategies to evade or attenuate host defenses. The UNC researchers discovered that one of these strategies involves secreting the protein SecA2, which prevents host cell apoptosis. Apoptosis is part of the innate immune response that hosts use to destroy their own infected cells thereby preventing further infection. Hosts then use antigens from bacteria in the destroyed cells to induce adaptive immune responses such as activation of cytotoxic CD8+ T-cells.
UNC researchers genetically engineered M. tuberculosis to be less virulent than naturally-occurring strains by eliminating SecA2 activity (ΔsecA2). Infection with ΔsecA2 allowed mouse hosts to develop better and longer-lasting immunity: the engineered bacteria-induced apoptosis and activated CD8+ T-cells. Vaccination with ΔsecA2 increased mouse survival vs. vaccination with bacilli Calmette-Guerin (BCG) control, and fewer virulent M. tuberculosis H37Rv grew in lungs and lymph nodes of ΔsecA2-vaccinated guinea pigs than in BCG-vaccinated guinea pigs. These data suggest that ΔsecA2 M. tuberculosis facilitates the development of immune responses and could be a critical component of a next-generation mycobacteria vaccine.
Name: Ruthie Arieti