Oct. 13, 2023
By Jordana Lenon
Five years after they reported a new macaque model for studying the pathology of tuberculosis (TB) in people living with HIV, researchers at the University of Pittsburgh and University of Wisconsin–Madison report how an alternative route of vaccination with Bacille Calmette-Guérin (BCG) can protect macaques with simian immunodeficiency virus (SIV) infection from TB. The National Institutes of Health Vaccine Research Center, National Institute of Allergy and Infectious Diseases also contributed to the research, published Oct. 9, 2023 in Nature Microbiology.
“This is a big step towards devising a vaccine strategy to protect people living with HIV from tuberculosis,” said Charles Scanga, senior author on the study, research associate professor of microbiology and molecular genetics at the University of Pittsburgh, and a member of its Center for Vaccine Research. Scanga and his department colleague Erica Larson, research assistant professor, collaborated with Shelby O’Connor, professor of pathology and laboratory medicine at the University of Wisconsin–Madison School of Medicine and Public Health, and the Wisconsin National Primate Research Center’s Virology and Genomics Services Units.
TB is caused by Mycobacterium tuberculosis (Mtb) and is the most common cause of death in people living with human immunodeficiency virus (HIV). While intradermal delivery of BCG is the only licensed vaccine against TB in humans, it offers little protection from pulmonary TB in adults. In addition, it is not recommended for people living with HIV because this live vaccine may cause disease in immunosuppressed individuals. 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.
A report in 2020 showed that intravenous administration of BCG conferred remarkable protection from TB in rhesus macaques. The current study demonstrates that vaccination with intravenous BCG can protect SIV-infected cynomolgus macaques from TB. “This is the first report of complete protection against TB in SIV-positive monkeys,” Scanga said.
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 completely protected, without any Mtb bacteria detected in tissues. Blood tests also indicated that the vaccine worked by promoting early clearance of Mtb in vaccinated animals, whether they were infected with SIV or not. The authors noted that the three SIV-positive vaccinated animals that did develop TB had higher SIV levels in their blood, further highlighting the importance of identifying and treating people with HIV infection.
All intravenously vaccinated animals were treated with anti-mycobacterial drugs beginning within four weeks of vaccination to reduce the risk of disseminated BCG disease. Disseminated BCG following intradermal vaccination in humans is rare, with a frequency of approximately one case per million vaccinations, according to the National Institutes of Health, but is a larger risk in immunocompromised recipients. Despite killing all BCG live vaccine within four weeks of intravenous vaccination, the strong immune response elicited complete, lasting protection in all SIV-naive macaques and in most SIV-positive macaques.