In June 2010 we ran a blog post about the International Tuberculosis Campaign, a post-WWII effort that TB tested and vaccinated tens of millions of people in 23 countries. The tenor of the campaign was optimistic and heroic, evident in this 1948 radio announcement from the president of the Danish Red Cross: “The spirit of the Nordic Vikings has been part of this campaign as in the old days. Earlier we went out sword in hand to conquer and fight each other. Today we go out together with the needles as our only weapon to fight the scourge of the Second World War: tuberculosis” (Brimnes 2007).
Despite the wide reach of that promising campaign, tuberculosis today is an enormous global problem, with 1.4 million deaths from the disease and 9 million new cases a year. The disease orphans millions of children and robs individuals and communities of vital earning capacity. Worryingly, each year more than 500,000 cases of multidrug-resistant TB occur, and in December 2011 several cases of completely drug resistant TB were reported in India. Emergence of resistant strains of TB highlights the need for effective TB vaccines to try to prevent infection entirely.
The TB current vaccine (bacille Calmette-Guerin, or BCG), which has been in use since the 1920s, protects children only from severe, progressive TB, and it is not safe for infants who are infected with HIV. BCG does not prevent pulmonary TB in teenagers and adults and therefore does not inhibit transmission among people. A new vaccine, or a collection of new vaccines, is needed.
As the TB non-profit Aeras says, “ideal vaccine regimens must protect babies at birth from childhood TB, and prevent infection with the organism in older children and adult.” Another goal of a new vaccine is to halt the progression of disease in the huge number of people who are already infected with tuberculosis.
In “Tuberculosis Vaccines: A Strategic Blueprint for the Next Decade,” Michael J. Brennan (Aeras) and Jelle Thole (Tuberculosis Vaccine Initiative) outline the challenges to developing new TB vaccines. Many of them are similar to the challenges to developing HIV vaccines: for example, the authors state “we still have a profound lack of understanding of what constitutes protective immunity in different age groups and populations against TB. In addition, there is no correlate or surrogate endpoint of protective immunity, so the success of new TB vaccines cannot be predicted or identified in experimental animal models or early clinical trials, thus necessitating evaluation of efficacy against clinical endpoints in long, protracted and costly clinical trials.”
Brennan and Thole delineate what they see as critical elements of developing safe, effective TB vaccines, including a need for creativity in research that extends to novel vaccine approaches, developing better animal models for understanding disease progression and protection, and understanding mechanisms of protective immunity in TB. The authors note that although most thinking on protective immunity for TB has focused on T cell response, antibody responses to TB should be explored, particularly in relation to development of possible transmission-blocking vaccines.
The authors suggest that progress is also needed in clinical trial design and conduct; for example, they urge the use of adaptive trial design so that ineffective or problematic vaccines can be quickly dropped and effective ones can be advanced productively. Additionally, they note that because of the unique demands of clinical trials of TB vaccines (that is, the vaccines need to be tested where TB infection incidence is high but where HIV infection incidence is low), it seems likely that only two candidate vaccines could be tested at one time.
Aeras announced on March 15, 2012, that it received a grant of $220 million over five years from the Bill & Melinda Gates Foundation. The funding will help Aeras move several of candidate vaccines further along the development pipeline. Though TB is at an all-time low in the United States, the global picture is clear: the TB vaccine problem is deserving of the same kind of international effort that animated the International Tuberculosis Campaign after World War II.
Aeras. Award to Aeras boosts historic hunt for new vaccines against TB, as drug-resistant strains proliferate. http://www.aeras.org/newscenter/news-detail.php?id=1188
Brennan MJ, Tholle J. Tuberculosis vaccines: A strategic blueprint for the next decade. Tuberculosis 9251 (2012) S6-S13.
Brimnes N. Vikings against tuberculosis: The International Tuberculosis Campaign in India, 1948-1951. Bull Hist Med. 2007; 81:407-430.
Final Report of the International Tuberculosis Campaign, July 1, 1948–June 30, 1951. Copenhagen: The International Tuberculosis Campaign, October, 1951.