CSU 56/2010: THE SEARCH FOR NEW TB VACCINES

Tuesday, 11th of May 2010

Discussion on new TB vaccines is a hardy perennial. Will it finally bear fruit? That is the view of Svenson and colleagues, from the Karolinska Institute, writing on ‘Towards new tuberculosis vaccines.' Here they write about the size of the growing TB problem and the inadequacy of BCG:

'Currently there are globally 9.15 million recorded cases of overt tuberculosis (TB) annually and due to lack of adequate diagnostics presumably a large but unknown number of non-recorded cases. TB is estimated to cause 1.65 million deaths per annum which accounts for one-fifth of all deaths by infectious diseases of adults in low-income countries. During recent years a rapid spread of multi-drug resistant bacteria causing about 0.5 million TB cases per year has worsened the problem. The live attenuated Bacillus Calmette-Guérin (BCG) vaccine which is the only currently available TB vaccine does not confer any significant protection against the most common and contagious form of TB-adult pulmonary TB.'

Here, their list of desired properties of a new TB vaccine:

Preferentially non-live i.e., killed or subunit type (increased stability, no cold chain needed, risk of reversion and liability problems are limited/avoided)

If subunit, it should contain several targets from mycobacteria including essential proteins as well as carbohydrate antigens

Should be delivered in such a manner that it evokes relevant cellular (and humoral) immune responses systemically as well as mucosally, in particular in respiratory tract

Should elicit a strong TH-1 response and, if needed, a non-toxic adjuvant should be used that supports such responses

Should be efficient not only as a primary vaccine but preferentially as a booster vaccine in the young adolescent after primary BCG vaccination.

The authors' Table 3 lists 22 ongoing or completed trials of candidate TB vaccines. The list of the countries conducting the trials gives an idea of the breadth of interest: in addition to developing countries in Africa and Asia, trials are either completed or underway in the US, the UK, and four countries of continental Europe.

Finally, their comments on the vaccine developers:

'Most of this research and development has been performed by academia and non-profit organizations such as Wellcome trust, Aeras global TB Vaccine Foundation (http://www.aeras.org) rather than by the big pharmaceutical companies with the exception of GlaxoSmithKline.'

Should the next generation of TB vaccines be administered by injection? The authors make a good case for ‘no,’ especially in terms of protection from pulmonary TB.

Full text at http://www.landesbioscience.com/journals/vaccines/article/SvensonHV6-4.pdf

Good reading.
BD