Tuberculosis (TB) remains the bacterial disease with the greatest impact worldwide, with nearly 10 million new cases each year, as well as the unfortunate death of 1.5 million people annually. On previous occasions I have mentioned that there are various efforts to replace or reinforce the only vaccine available today against TB: the attenuated bacterium (does not cause disease in immunocompetent people) Mycobacterium bovis Bacillus Calmètte-Guèrin, known as BCG.
Among the main limitations of BCG are:
It has variable efficacy of protection against pulmonary TB, which occurs in 80% of cases. The duration of immunity conferred by intradermal BCG vaccination is estimated to be around 20 years or less. In practical terms, BCG is considered a single vaccine, when in fact there are at least 15 variants of it. In addition, around 5 different versions of BCG are applied worldwide, which have already been shown to differ in their ability to induce an immune response in blood cells obtained from vaccinated donors (ex vivo), suggesting that this could impact on different capacities to protect against TB.
Today, the BCG vaccine is applied by means of an intradermal injection. As the natural route of infection by Mycobacterium tuberculosis is airborne, various studies have evaluated the hypothesis that using immunization by this route and imitating the regular route of access of the pathogen to humans would result in better protection against the disease. Due to time as well as space, in addition to being the research model closest to us, I will only mention that various works carried out in non-human primates have shown, in general, that there would be better protection against TB when administering BCG by air compared to current vaccination by intradermal route. However, in some cases the improvement was marginal, which leads to the obvious need to add ethical considerations (will possible adverse effects in people be increased if BCG is immunized via the air, compared to intradermal?) to practical issues (¿ how to achieve a successful administration of the dose without causing major discomfort to those who receive BCG by air?) to define if this route of administration could reduce the damage caused by TB. There are already studies in smaller models (mice and guinea pigs) where attempts have been made to reduce the residual virulence of BCG via the removal of surface lipids or genetic modifications that further attenuate this vaccine, such as our candidate, BCGΔBCG1419c, of course, without lose their protective efficacy, but on the contrary, better protect against TB.
With this state of affairs in the field of research on how to improve the protection conferred by BCG, and taking up studies dating back half a century, another group recently compared, in non-human primates, the protection against TB conferred by BCG applied by various routes: intradermal (in 2 different doses), aerosol, and intravenous. Quite strikingly, intravenous BCG vaccination resulted in the best protection against the disease, both pulmonary and disseminated. Subsequent studies have contributed to suggest various factors of the immune response as possible determinants of protection. The feeling of renewed optimism about vaccinating with intravenous BCG was such that, in the opinion of various experts, a pause is warranted in order to consider, among other factors necessary before arriving at new clinical studies, at least the following questions:
Will possible adverse effects in people be increased if BCG is immunized intravenously, compared to intradermally? In non-human primates, various generally minor and tolerable reactions occurred. However, one must bear in mind the fact that the reports to date include results derived from controlled conditions (a single BCG strain tested out of several in use in humans, a single strain of Mycobacterium tuberculosis that does not necessarily reflect the variety of these circulating globally, a single type of non-human primates -rhesus monkeys- that do not reflect the heterogeneity seen in humans). What will happen to protection against TB if people from different countries are vaccinated intravenously and are infected with strains of Mycobacterium tuberculosis of variable virulence? What will happen to the guidelines set by the regulatory authorities of each country? Which countries would agree to clinical studies being conducted in them?
Without a doubt, the discussion of these issues between researchers, pharmaceutical companies and regulatory entities deserves to be carried out in order to be clear about the best course of action in order to promote better health and care for this disease.
2023-07-13 00:33:00
#intravenous #BCG #vaccination #combat #tuberculosis #future
