Vaccines: Early and Late Protection from TB

ReseaRch highlights

In the early stage of infection vACCINES (<4 weeks after exposure), the mycobacterial loads in the lungs of H56-vaccinated mice were similar Early and late protection to those of mice vaccinated with the BCG vaccine. However, in the later stage of infection (24 weeks after from TB exposure), H56-vaccinated mice had significantly lower numbers of bacilli than BCG-vaccinated mice. Moreover, H56 was an effective booster to BCG, as mice that received the booster had significantly lower bacterial loads 24 weeks after infection than mice vaccinated with BCG alone. Importantly, in two mouse models of latent tuberculosis, H56 provided significant protection against reactivation of the disease. Detailed examination showed that H56 promoted the generation of antigen- specific, polyfunctional CD4+ T cells in the lungs. These T cells, which were shown to express interferon-γ, interleukin-2 and tumour necrosis factor, are thought to be important The one approved vaccine late-stage infection in both pre- and for the quality and endurance of the against tuberculosis (known as post-exposure mouse models. immune response. the Mycobacterium bovis bacillus The vaccine (termed H56) Together, these data show that Calmette–Guérin (BCG) vaccine) comprises a fusion protein immunization with an antigen that and those currently in clinical tri- (Ag85B–ESAT6–Rv2660c) and is expressed during the late stages als are designed to protect against a cationic adjuvant (CAF01). of tuberculosis (together with early- initial infection, as they incorporate Ag58B and ESAT6 are well known stage antigens) enhances contain- Mycobacterium tuberculosis antigens M. tuberculosis antigens that are ment and prevents reactivation of the that are expressed early in the dis- secreted early in infection and have disease. The Statens Serum Institut, ease process. However, they do not previously been shown to provide Denmark, have reported that H56 prevent the establishment of latent protective immunity. Rv2660c was will enter clinical trials in South persistent infection or the reactiva- identified in this study as one of the Africa in March 2011. tion of clinical disease — a major factors expressed at constant levels Man Tsuey Tse need both for infected patients and throughout infection. The authors Locum Assistant Editor, for reducing further transmission. proposed that simultaneous vaccina- Nature Reviews Drug Discovery Reporting in Nature Medicine, tion with these three antigens could

Aagaard and colleagues show that a produce multistage effects, enabling ORIGINAL RESEARCH PAPER Aagaard, C. et al. vaccine containing antigens that are the immune system to mount a A multistage tuberculosis vaccine that confers expressed in the early and late stages response to both the early and late efficient protection before and after exposure. Nature Med. 17, 189–194 (2011) of tuberculosis protects against phases of tuberculosis.