Latest Tuberculosis Vaccine Results Unveiled at FAPESP Week China

The Butantan Institute, in collaboration with a number of other researchers, has made significant strides towards creating a more potent version of the BCG vaccine used to combat tuberculosis. While traditional vaccines have been shown to reduce infection by 90% in lab mice, this new recombinant BCG alternative increases that protection rate up to an impressive 99%. Additionally, it also offers longer-lasting protection. 
 
Researchers are particularly interested in strengthening the efficacy and longevity of this vaccination due to current issues surrounding antibiotic resistance. The existing immunity provided by conventional immunizers tends to diminish over time, especially into adulthood. As Luciana Cezar de Cerqueira Leite from Butantan Institute's Vaccine Development Laboratory explains, "BCG is the first vaccine we receive at birth, and it's indeed effective in protecting children... But immunity against the disease tends to wane in adulthood." 
 
To comprehend why recombinant BCG provides such enhanced results compared with its conventional counterpart, these researchers adopted a systems biology approach. This involved observing gene behavior across different tissues throughout immune response assembly within animal models. 
 
In her presentation at FAPESP Week China on June 29th, dedicated largely to health and biomedicine discussions, Cerqueira Leite outlined their process: "We sequenced all the RNA that was expressed and present in samples taken at different times." These sample groups consisted of non-immunized mice, those given conventional BCG, and those vaccinated with recombinant BCG. 
 
An early revelation was seen seven days post-immunization, where approximately 200 genes were activated among recipients of recombinant vaccines while virtually no change occurred within the conventionally-vaccinated group. 
 
This research has revealed two key points about these vaccines: they function via markedly different metabolic pathways, which have now been mapped out; moreover, after just three months post-vaccination, the immune response begins declining for those who received regular vaccinations, whereas it remains stable for those given the recombinant version. 
 
The BCG vaccine was developed over a century ago by attenuating Mycobacterium bovis, the bacterium responsible for bovine tuberculosis. The genetically engineered recombinant variation has been endowed with the capability to produce a fragment of a toxin originally secreted by Escherichia coli, another common species found in human intestines. 
 
According to Leite, "Some E. coli bacteria produce heat-labile toxins, which are highly immunogenic. In the recombinant vaccine, we use a detoxified fragment of the LT toxin [called LTAK63]. It isn't capable of causing disease, but it maintains immunogenicity." 
 
Successes achieved through studies utilizing this new vaccination strategy have led researchers to apply this same platform to developing improved vaccines against numerous conditions, including whooping cough, pneumonia (caused by Streptococcus pneumoniae or pneumococcus), and schistosomiasis, as well as potentially treating bladder cancer. 
 
Leite explains that during animal model trials, using recombinant BCG resulted in reduced bacterial presence within the lungs and less inflammation overall—benefits she attributes to their detailed understanding of how these two different vaccines function.