100% prevention of tuberculosis? It can be done only by changing the method of administration!

BCG vaccination is known as "the first injection at birth", which should be given to newborn babies in delivery hospitals and obstetrics departments as soon as they are born However, BCG vaccination does not mean complete prevention of tuberculosis infection Recently, Darrah and other researchers from the vaccine research center of the National Institutes of health allergy and infectious diseases have proved that a widely used tuberculosis vaccine can provide almost complete protection when injected intravenously This is a significant improvement over traditional intradermal vaccination The report was published in nature Tuberculosis is the most deadly human infection, killing 1.5 million people in 2018 alone It is generally believed that an effective anti Mycobacterium tuberculosis vaccine will be the most effective way to control the disease However, pathogens often resist the immune response caused by vaccines The latest research shows that a vaccine with a history of one hundred years can almost completely prevent tuberculosis infection by changing the way of administration The main targets of BCG vaccination are newborns and infants, which can prevent tuberculosis in children However, its ability to prevent adult tuberculosis has not been satisfactory Despite these limitations, BCG vaccine is still the only vaccine to provide protection against tuberculosis in large-scale triple immunization BCG is usually injected into tissues below the skin's epidermis, a convenient injection site that contains special cells that stimulate the immune response However, vaccines that activate immune cells at potential sites of infection can more effectively destroy invading pathogens Therefore, the current immunology view is that vaccines injected directly into the lungs or upper respiratory tract will be better in preventing pulmonary infection (including influenza and tuberculosis) Here, Darrah and his colleagues studied whether different routes of administration of BCG vaccine could improve the protection of tuberculosis Darrah et al Used rhesus monkeys because their TB infection is closely related to human disease They evaluated five vaccination strategies The methods of BCG vaccination in animals are as follows: standard dose by conventional intradermal injection; intradermal injection higher than normal dose; pulmonary injection by aerosol; combination of high-dose intradermal injection and aerosol injection; or intravenous injection After six months of vaccination, the author exposed macaque to Mycobacterium tuberculosis and paid close attention to the development of the disease, so as to determine how the route and dose of vaccination affect the prevention of infection It is found that intradermal or aerosol vaccination can only prevent tuberculosis at best In contrast, intravenous vaccines can almost completely prevent the disease It is worth noting that of the 10 animals that received the IV vaccine, 6 did not find any trace of the pathogen, indicating that the infection has been prevented or eliminated The other three monkeys also showed a high degree of protection Therefore, the route of BCG vaccination obviously affects the immunity, and the intravenous route is the most effective way to prevent tuberculosis so far What makes intravenous BCG vaccination so effective? Intravenous BCG can make a lot of immune T cells flow into the lung Six months later, when animals were exposed to Mycobacterium tuberculosis, the number of T cells was still increasing This dilation is most likely due to the introduction of large doses of BCG into the lungs by intravenous injection The researchers also demonstrated that T cells can recognize protein fragments called antigens produced by BCG Because BCG and Mycobacterium tuberculosis are closely related bacteria, these T cells can also recognize Mycobacterium tuberculosis antigen According to its gene expression profile, surface protein and its function, T cells entering the lung differentiate into "memory" T cells These T cells survive for a long time after vaccination, because they can recognize the antigens produced by Mycobacterium tuberculosis, they can be activated rapidly when they are infected, and produce many "effect" T cells to fight against the invading pathogens Whether intravenous BCG vaccine will be developed for clinical application or not, research based on Darrah's and colleagues' work may help to better understand the prevention effect of tuberculosis In the future, we will continue to study the immune mechanism triggered by intravenous BCG If successful, we may develop a vaccine designed to activate the same protective immune mechanism as that triggered by intravenous BCG However, this vaccine is safe and can adapt to large-scale vaccination programs.