The standard intradermal route of delivery for Bacille Calmette–Guérin (BCG) does not necessarily generate a strong enough response from lung T-cells, the researchers say. They hypothesized that administering BCG by IV or aerosol might be more effective.
They gave a group of rhesus macaques the BGC vaccine by intradermal, aerosol, or IV routes, then assessed immune responses in blood and fluid drawn from the lungs over a 24-week follow-up. Six months after vaccination, the researchers injected the vaccinated animals with a virulent strain of Mycobacterium tuberculosis (M tuberculosis) and tracked infection and disease development over 3 months.
The IV vaccination resulted in the highest durable levels of T-cells in blood and lungs. Nine of 10 animals vaccinated via IV were highly protected; 6 showed no detectable infection in any tissue tested and 3 had only very low counts of M tuberculosis in lung tissue. All unvaccinated animals and those immunized via intradermal or aerosol routes showed signs of significantly greater infection.
Upping the dose did not improve protection. The IV BCG group showed 90% protection at a threshold as low as 50 colony-forming units (the standard human ID dose is 5 x 10 5 CFUs).
The researchers say several unique quantitative and qualitative differences in the immune responses may underlie protection. Perhaps most noteworthy, they say, was the large population of T- cells in the tissue across all lung parenchyma lobes.
The study provides a “paradigm shift,” the researchers conclude, adding that the IV route may also improve the protective capacity of other vaccines.