Infection with Mycobacterium tuberculosis continues to be a major public
health burden in most developing parts of the world and efforts to
develop effective strategies for containing the disease remain a
priority. It has long been evident that effective mass vaccination
programmes are a cost effective and efficient approach to controlling
communicable diseases in a public health setting and tuberculosis (TB)
continues to be a major target. One approach with increasing acceptance
is based upon on live mycobacterial vaccines, either as recombinant BCG
or rationally attenuated M. tuberculosis, thus generating a new live TB
vaccine. The Geneva Consensus published in March 2005 set out the
opinion on priorities and requirements for developing live mycobacterial
vaccines for Phase I trials. In the intervening period much progress has
been made in both preclinical and clinical development of new TB
vaccines and has provided the impetus for organising the second Geneva
Consensus (held at WHO headquarters, April 2009) to discuss issues,
i. Explore the regulatory requirements for live TB vaccines to enter
Phase I trials, in particular those based on attenuated M. tuberculosis.
Particular attention was paid to the characterisation and safety package
likely to be required, including issues of attenuation, the presence of
antibiotic resistance markers in live vaccines and the nature of any
attenuated vaccine phenotype.
ii. To identify the general criteria for further clinical development
from Phase I through to Phase III.
iii. Obtain a perspective of the regulatory landscape of developing
countries where Phase II and III trials are to be held.
iv. Review manufacturing considerations for live TB vaccines and
relevance of the WHO and European Pharmacopeia guidelines and
requirements for BCG vaccine.
v. Consider requirements and associated issues related to the use of
these new vaccines within an existing BCG vaccination programme.
Walker, K.B.; Brennan, M.J.; Ho, M.M.; Eskola, J.; Thiry, G.; Sadoff, J.; Dobbelaer, R.; Grode, L.; Liu, M.A.; Fruth, U.; Lambert, P.H. The second Geneva Consensus: Recommendations for novel live TB vaccines. Vaccine (2010) 28 (11) 2259-2270. [DOI: 10.1016/j.vaccine.2009.12.083]
The second Geneva Consensus: Recommendations for novel live TB vaccines