Tuberculosis is one of the leading infectious causes of morbidity and mortality across the world. In 2020 it killed 1.5 million people and caused 10 million new infections. It also has a disproportionate case burden of two-thirds in 8 countries. Although there is a vaccine, the Bacillus Calmette-Guérin (BCG), it has limited efficacy in adults. NIH reports that BCG is “only partly effective”.
Thus, there is a great medical need for an update to our tuberculosis strategy, and although adjuvanted subunit vaccines have “shown promise” in testing, they require refrigeration. This is “costly” and “difficult in low-resource areas”. Therefore, research into a more thermostable vaccine is required, and a team from the US took on the challenge with results published in Nature Communications in March 2023.
The TB burden
Tuberculosis (TB) is caused by infection with Mycobacterium tuberculosis bacteria. Although it primarily affects the lungs, it is also known to affect other areas such as the kidney, spine, or brain. When untreated or inadequately treated it is deadly. However, it is both curable and preventable, according to WHO.
WHO reports that, although TB occurs in “every part of the world”, greatest number of new cases was observed in the WHO South-East Asian Region in 2021. The second most affected region was the WHO African Region, followed by the WHO Western Pacific.
Context of the study
The authors of the study identify “progress” in the “rational selection of antigens made more immunogenic by the combination with vaccine adjuvants”. However, they state that there are “no thermostable adjuvanted subunit TB vaccine candidates” in development.
“Considering the enormous worldwide burden of TB, particularly in Southeast Asia and Sub-Saharan Africa, a thermostable vaccine could provide substantial advantages for global vaccine distribution.”
Establishing a need is one thing, and although “various technologies” can be used to increase a vaccine’s thermostability, there is “substantial complexity” to adapting these technologies for vaccines containing adjuvants.
A major step forward
The Phase I study was a randomised, double-blind clinical trial, designed to “evaluate the safety, tolerability, and immunogenicity” of a single-vial lyophilised ID93 + GLA-SE vaccine candidate in comparison with a previously developed two-vial presentation in healthy adult subjects. The results demonstrate a “similar safety profile” alongside a “comparable or improved immunogenicity profile”.
“The present report represents a major step forward for the field of thermostable lyophilised adjuvant-containing vaccine candidates.”
The authors recognise that some formulations with “thermostable properties” have progressed through testing and licensure, with “significant beneficial impact”. However, the stability of these vaccines outside refrigerated temperatures is “limited to days or a few weeks”. By contrast, the thermostable single-vial presentation of ID93 + GLA-SE is “stable for 3 months at 37°C.
As is always the case in vaccine development, cost is an “important consideration”. The researchers estimate that the excipient cost of the thermostable presentation would be “approximately $0.15 more per dose than the non-thermostable composition at commercial scale”. Additional costs are associated with the “multi-day lyophilisation processing time”.
However, the authors suggest that these costs will be mitigated by “anticipated cost savings and reduced wastage” from the “less stringent storage requirements of the thermostable formulation”.
Study author Dr Corey Casper, President and CEO of the Access to Advanced Health Institute, says that “equitable access to vaccines has been significantly impeded” by refrigeration requirements.
“As observed with COVID-19, no one is safe until everyone is safe.”
We will hear more from speakers such as Dr Mark Feinberg and Dr Jerome Kim in a World Vaccine Congress panel on “silent, forgotten, and underfunded” diseases that persistently cause tragic deaths before, during, and after the COVID-19 pandemic. To join us, get your tickets here.