Medical researchers have discovered a new route of administering the vaccine, Bacille Calmette–Guérin (BCG) that may confer more protection against tuberculosis when injected differently. This vaccine, which has been used for almost a century is typically given as an injection just under the skin.

But Patricia A. Darrah of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA writing in the journal, Nature have stated that the widely used vaccine against tuberculosis provides almost complete protection when injected intravenously, what they say is “a striking improvement over vaccination through the typical intradermal route.”

Tuberculosis regarded as one of the deadliest human infection, was responsible for the death of over 1.5 million people in 2018 alone. The dodgy nature of the pathogen, which easily develops resistance to the immune responses created by vaccination has been a major hurdle to effective control of the diseases globally.

The authors of the latest work in Nature stated that this has raised the question of whether it is possible for a conventional vaccine to confer sterilizing immunity against TB — a gold-standard immune status for vaccines, under which disease is prevented and the pathogen completely eliminated, often before it can even establish a productive infection.

Darrah et al noted that it provides a resounding answer to this question by showing that “near-complete protection from TB infection can be conferred using a century-old vaccine, simply by changing its route of administration.”

The BCG vaccine has been effective against some deadly early-childhood forms of TB. However, its ability to prevent the transmissible pulmonary form, which is the dominant form in adults, has been patchy, as it has been found to confer protection for some groups of people in some countries, but is generally insufficient to reduce the number of active TB cases in countries where the infection is endemic. Despite these limitations, BCG remains the only TB vaccine to confer protection in large-scale trials.

“BCG is typically given as an injection into the dermal tissue that lies just beneath the outer layer of the skin,” the nature article stated.

“This injection site is convenient and contains specialized cells that stimulate immune responses, However, vaccines that activate immune cells at the site of potential infection can be more effective at destroying invading pathogens. Thus, current immunological thinking suggests that vaccines administered directly into the lung or the upper airways would be better at preventing pulmonary infections, including influenza and TB.”

According to the authors, two billion people worldwide are infected with Mycobacterium tuberculosis, with 10 million new cases of active tuberculosis (TB) and 1.7 million deaths each year.

They stated that prevention of pulmonary infection or disease in adolescents and adults would have the largest effect on the epidemic by controlling Mtb transmission.

“The only licensed TB vaccine, BCG (live, attenuated Mycobacterium bovis), is administered intradermally at birth and provides protection against disseminated TB in infants but has variable efficacy against pulmonary disease in adolescents and adults,” Darrah and colleagues wrote.

They have investigated whether a different route of BCG administration could improve protection against pulmonary TB. They performed their analysis using rhesus macaques, because TB infection in these monkeys closely mirrors the human disease. They evaluated five vaccination strategies. Animals were given the BCG vaccine at the standard dose through the conventional intradermal route, at a higher-than-normal dose intradermally, by means of an aerosol to inoculate the lung, through a combination of the high dose and inoculation by aerosol or through an intravenous injection.

The authors exposed the macaques to M. tuberculosis six months after vaccination, and tracked disease progression to determine how the administration route and dose of the vaccine affected protection against the infection.

They found that vaccinations given intradermally or by aerosol conferred, at best, modest protection from pulmonary TB. But in contrast, intravenous vaccination afforded nearly complete protection from the disease. The researchers could not detect any trace of the pathogen in six out of ten animals that received the intravenous vaccination, indicating that the infection had been either prevented or cleared. Three of the other monkeys also showed high levels of protection.

This finding by Darrah and colleagues has raised the optimism level about the possibility of controlling TB by giving people BCG by intravenous injection.

Whether or not intravenous BCG is developed for clinical use, research that builds on Darrah and colleagues’ work could lead to an improved understanding of what protection against TB looks like nature writes.

Read full article in nature


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