An Attenuated Mycobacterium Tuberculosis Vaccine Candidate Provides Strong Protection Against Tuberculosis
New research shows promise for tuberculosis (TB) prevention using a new vaccine candidate, ΔsigH, which has demonstrated superior effectiveness over the current BCG vaccine.
Despite substantial global efforts to combat HIV, tuberculosis remains one of the deadliest infectious diseases, claiming over 1.3 million lives annually. The BCG vaccine, the only licensed vaccine for TB, has shown inconsistent efficacy, particularly against adult forms of the disease. Consequently, researchers have turned to developing new vaccination strategies aimed at overcoming these limitations.
This recently published study highlights the significant success of the ΔsigH mutant strain of Mycobacterium tuberculosis when administered as a mucosal vaccine to cynomolgus macaques. Initial trials indicate this vaccine candidate could be pivotal for TB prevention.
The ΔsigH strain is strategically engineered to be attenuated and unable to mitigate oxidative stress, which compromises its survival ability during infection. The absence of this regulatory gene significantly enhances the immune response elicited by the vaccine. The research team vaccinated twenty-five cynomolgus macaques with ΔsigH via aerosol and then challenged them with 100 CFU of Mtb CDC1551 eight weeks later.
Researchers observed remarkable outcomes from the ΔsigH vaccination. None of the vaccinated animals developed active TB symptoms, such as weight loss or respiratory issues, highlighting the vaccine's safety profile. Significant protective immune mechanisms were noted, characterized by increased recruitment of antibodies and T cells to the lungs, which are integral for fighting TB. The vaccination led to the generation of inducible bronchus-associated lymphoid tissue, indicating the formation of enhanced immune niches within the lungs.
The induced immune response was marked by high levels of interferon-gamma (IFNG) production from antigen-specific CD4+ and CD8+ T cells, reflecting active protection mechanisms at play. The study determined ΔsigH-vaccinated macaques demonstrated significantly lower levels of Mycobacterium tuberculosis, with lung bacteria burdens four logs lower than those observed among unvaccinated controls. This finding emphasizes its potential power as a protective vaccine strategy against TB.
By exploring immune cell responses post-vaccination, researchers identified the vaccine enhanced the activity of T cells derived from the lungs. This nuanced interplay suggests ΔsigH may facilitate not only immediate responses but possibly longer-lasting immunity against TB, addressing one of the most pressing challenges with the BCG vaccine.
"Vaccination with ΔsigH resulted in significantly greater frequency (>75%) of lung lobes to be sterile, indicating less disease burden compared to the control groups," reported the authors of the study. This prevention is noteworthy, especially since the BCG vaccine traditionally yields limited results against pulmonary TB.
Long-term, the results of this study could inform vaccine development frameworks for human populations, particularly targeting areas where TB prevalence remains high. The promising findings lay the groundwork for moving toward human clinical trials, as researchers aim to fine-tune and bolster the safety profile of ΔsigH before human application.
Overall, the research showcases the potential of ΔsigH as a next-generation TB vaccine candidate. It stands as part of the continuing efforts to develop effective immunizations against diseases with significant public health challenges, representing hope for improved TB control strategies.