Immunological Outcomes of New Tuberculosis Vaccine Trials: WHO Panel Recommendations

Abstract

Willem Hanekom and colleagues make recommendations on assay harmonization for novel tuberculosis vaccine trials.

Individual-level factors associated with variation in mycobacterial-specific immune response: Gender and previous BCG vaccination status

“…Whilst the presence of IFN-g has been shown to be important in protection against M.tb infection [31], it has not proven to be a correlate of protection for TB disease [32,33]. It is, however, one of the most commonly used measures of TB vaccine immunogenicity we have [34]. The use of IFN-g-expressing cells as our sole indicator of immunogenicity has benefits in its simplicity, and was the only outcome for which data was available to us.…”

“…The use of IFN-g-expressing cells as our sole indicator of immunogenicity has benefits in its simplicity, and was the only outcome for which data was available to us. Other studies are being carried out that may give a more in depth view of the immune response to BCG in which a more complex "biosignature" is being investigated [34]. Secondly, our work was limited to the data available from the seven TB vaccine trials, which restricted the covariates available and the size of the participant cohorts.…”

Multifunctional T Cell Response to DosR and Rpf Antigens Is Associated with Protection in Long-Term Mycobacterium tuberculosis-Infected Individuals in Colombia

“…Most studies evaluating T cell responses to M. tuberculosis DosR and Rpf antigens in LTBI and PTB have been based on IFN-␥ detection (31, 32, 34, 35, 40, 52-54). Here, we used a 7-day stimulation assay to optimize sensitivity to detect latent infection, since short-term cultures (25, [55][56][57] are less sensitive in settings of high levels of endemicity, where mixtures of recent and old infections are commonly found (55). Figure 2 and Table 2 show the responses of CD4 ϩ T cells to E6-C10 and DosR and Rpf antigens.…”

“…Although in other studies higher frequencies of mono-and bifunctional CD4 ϩ T cells producing IFN-␥ and/or TNF-␣ in response to RD1 were found in PTB, compared to LTBI (18,19,27,28), the difference in the lengths of the in vitro cultures might explain this difference. Short-term cultures (24 h) have been mainly associated with the detection of a T cell effector memory phenotype, while long-term cultures (5 to 7 days), as used in this study, have been mainly associated with the detection of a T central memory phenotype (25,36,56,57,64). An alternative explanation for the observed reductions in the frequencies of monoand bifunctional CD4 ϩ T cells in peripheral blood samples from PTB patients may involve the previously reported sequestration of CD4 ϩ T cells at the site of infection (65,66).…”

Mycobacterium tuberculosis antigen 85B and ESAT-6 expressed as a recombinant fusion protein in Mycobacterium smegmatis elicits cell-mediated immune response in a murine vaccination model

“…Improved vaccines are urgently needed, particularly to target the global epidemic of adult active TB, which is the most infectious form of the disease (Hanekom et al, 2008). During the last few years, a number of new candidate vaccines against TB have now been trailed, with several vaccines showing improved efficacy (Andersen, 2007).…”