Oct. 11, 2023
By Jordana Lenon
Five years after they reported a new macaque model for studying the pathology of tuberculosis in AIDS patients, a team of researchers at the University of Pittsburg, with support from the Wisconsin National Primate Research Center’s Virology and Genetics Services Units, reports a new vaccine that prevents macaques with simian immunodeficiency virus (SIV) infection from acquiring tuberculosis. The National Institutes of Health Vaccine Research Center, National Institute of Allergy and Infectious Diseases, also contributed to the research, which was published Oct. 9, 2023 in Nature Microbiology.
Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), is the most common cause of death in people living with human immunodeficiency virus (HIV). While intra-dermal delivery of BCG is the only licensed vaccine against tuberculosis in humans, it offers little protection from pulmonary tuberculosis in adults and is not recommended for people living with HIV. The vaccine is not widely used in the United States; however, it is often given to infants and small children in other countries where TB is common, according to the Centers for Disease Control.
With this new discovery, the researchers report that intravenous administration of Bacille Calmette-Guérin (BCG) vaccination safely protects SIV-infected macaques from tuberculosis. The species is a long-established model for studying HIV infection and this is the first report of protection against TB in SIV-positive macaques.
Specifically, intravenous BCG elicited robust airway T-cell influx and elevated plasma and airway antibody titers in both SIV-infected and SIV-naive rhesus macaques. Following Mtb challenge, all 7 vaccinated SIV-naive animals and 9 out of 12 vaccinated SIV-infected animals were protected, without any culturable TB bacteria detected in tissues. Blood tests also showed early clearance of tuberculosis in vaccinated animals, whether they were infected with SIV or not. The authors noted that the three SIV-positive vaccinated animals that were unprotected from tuberculosis tended to have a higher viral load, suggesting more progressive SIV infections in those animals.
All vaccinated animals were treated with anti-mycobacterial drugs beginning within four weeks of vaccination as an added precaution against disseminated BCG infection. Disseminated BCG infection following vaccination in humans is rare, with a frequency of approximately one case per million vaccinations, according to the National Institutes of Health. In the monkeys, intravenous BCG-induced immune responses and protection were maintained in all SIV-naive macaques and in most SIV+ macaques. The researchers’ data indicate that any circulating BCG was killed naturally by the immune system soon after vaccination without loss of protection.