Recent Developments in Tuberculosis Vaccines

Dessislava Marinova; Jesus Gonzalo-Asensio; Nacho Aguilo; Carlos Martin


Expert Rev Vaccines. 2013;12(12):1431-1448. 

In This Article

Biomarkers in Preclinical & Clinical Setting

Development of an improved vaccine against TB is hindered by the lack of a surrogate of protection. Efficacy of new TB vaccines in humans can only be evaluated by expensive and time-consuming efficacy trials within TB endemic areas.[123] In experimental animal models of TB vaccination, IFN-γ-producing CD4+ Th1 cells have been a popular demonstration of vaccine immunogenicity as measured. In humans these observations are being made on the circulating pool of lymphocytes present in the blood.[6,23] Nevertheless, it is becoming more evident that IFN-γ production by CD4+ T cells may be important for controlling onset of TB disease, but it is not a clear correlate of vaccine-induced protection.[128] In the search for better correlates of vaccine-induced production, light is being shone on the stronger correlation between polyfunctional Th1 cells and protection given to the host. However, whether multifunctional T cells are the best clinical readout to predict TB vaccine efficacy is now however under scrutiny, following a trial in South African infants showing no correlation of multifunctional T cells with TB protection when analyzed 10 weeks post-BCG vaccination.[6,129]

It is critical that vaccines with the greatest potential to protect are selected for efficacy trials. Mycobacterial growth inhibition assays (MGIAs) have been developed with the hope to correlate data with protection in animals, which could aid in the selection of the best vaccine candidates.[130] More recently, a human challenge model using intradermal BCG administration in previously vaccinated individuals with BCG has been clinically tested with the idea to identify correlates of antimycobacterial immunity.[131] With a recently reported transcriptomic footprint specific for active disease in TB patients,[132] transcriptional profiling is becoming more and more frequent as an additional immunological approach in clinical trials of new TB vaccines, where gene expression signatures are compared in samples from various time points.[124] More recently, as presented at the Third Global Forum for Tuberculosis Vaccines in Cape Town, a study in South African adolescents conducted at SATVI identified a gene signature of risk of disease differentially expressed between TB cases and controls.[226] It is postulated that correlates of risk in adolescents could allow target enrolment in vaccine trials and guide studies of vaccination-induced correlates of protection against TB disease.[133] With the current state of the art, only efficacy data from Phase III clinical trials of new vaccines will help correlate clinical immunological data with vaccine-induced protection.