Robert Wilkinson, Friedrich Thienemann, the CIDRI team & international collaborators publish landmark candidate TB vaccine study

The results of a randomised, placebo-controlled phase 2 trial assessing the safety, immunogenicity, and efficacy of the candidate TB vaccine, MVA85A, in healthy adults infected with HIV-1, were recently published in The Lancet Respiratory Medicine. This landmark study was led by Professor Robert Wilkinson, Dr Friedrich Thienemann and the Clinical Infectious Diseases Research Initiative (CIDRI) team, as well as their international collaborators, led by Professor Helen McShane from the University of Oxford.

HIV-1 infection is associated with increased risk of tuberculosis and a safe and effective vaccine would assist control measures. They assessed the safety, immunogenicity, and efficacy of a candidate tuberculosis vaccine, modified vaccinia virus Ankara expressing antigen 85A (MVA85A), in adults infected with HIV-1.

This is the first time that a candidate tuberculosis vaccine has been assessed for efficacy against Mycobacterium tuberculosis infection in people infected with HIV-1. The results show that vaccinating adults infected with HIV-1 with MVA85A is safe, but does not confer protection against infection with M. tuberculosis.

Implications of all the available evidence:

Safety of MVA85A in this large study population of adults with HIV infection is an important finding for tuberculosis vaccine development. The vector is safe to give to people without HIV testing; with the safety data providing some generic reassurance that new candidate tuberculosis vaccines are safe in this higher risk population. Additionally, this study has shown that high-quality, multicentre tuberculosis vaccine trials in vulnerable populations are possible.

The absence of efficacy despite immunogenicity in this and previous clinical trials of MVA85A suggests that the current parameters for selection of tuberculosis vaccine candidates are inadequate. Standardised preclinical animal models that better represent human infection and of candidate vaccines direct to the respiratory mucosa, merit assessment. Other lessons learnt from this trial include the characterisation of the epidemiology of M tuberculosis infection and disease associated with HIV-1 infection in a setting of antiretroviral therapy and isoniazid chemoprophylaxis.