VACCINES Early and Late Protection from TB

RESEARCH HIGHLIGHTS

VACCINES Early and late protection from TB

The BCG vaccine (which is the only In the early stage of TB infection approved vaccine against tuberculosis (<4 weeks after exposure), the (TB)) and other TB vaccines that bacterial load in the lungs of are currently in clinical trials are H56‑vaccinated mice was similar designed to protect against infection to that of mice vaccinated with the by incorporating antigens that are BCG vaccine. However, in the later expressed early in the disease process. stage of infection (24 weeks after However, they do not prevent the exposure), H56‑vaccinated mice establishment of latent persistent had significantly lower numbers infection or reactivation of clinical of bacilli compared to BCG- disease, which is a major unmet need vaccinated mice. Moreover, H56 for infected patients and for reducing was an effective booster to BCG, further transmission. with H56‑vaccinated mice having Reporting in Nature Medicine, significantly lower bacterial loads Aagaard and colleagues show that a 24 weeks after infection compared to vaccine comprising antigens that are mice vaccinated with BCG alone. expressed in the early and late stages Importantly, in two mouse models of TB combated late-stage infection of latent TB, H56 provided significant in both pre- and post-exposure protection against reactivation of mouse models. the disease. Detailed examination The vaccine (termed H56) showed that H56 promoted the comprises a fusion protein generation in the lungs of antigen- (Ag85B–ESAT6 (a 6 kDa early specific, polyfunctional CD4+ T cells secretory antigenic target)–Rv2660c) expressing interferon-γ, interleukin‑2 and a cationic adjuvant (CAF01). and tumour necrosis factor, which Ag85B and ESAT6 are well-known are thought to be important in the inclusion of an Mycobacterium tuberculosis antigens quality and endurance of the immune antigen that is that are secreted early in infection; response. also expressed they have previously been shown to Together, these data show that in the late provide protective immunity, and the inclusion of an antigen that is an Ag58B–ESAT6 fusion protein is also expressed in the late stages of stages of TB currently in clinical trials. TB can enhance containment and can enhance Rv2660c, which is known to prevent reactivation of the disease. containment be involved in the stress response, The Statens Serum Institut in and prevent was identified in this study as one Copenhagen, Denmark, has reported reactivation of of the factors that is expressed at that H56 will enter clinical trials in the disease constant levels throughout the stages South Africa in March 2011. of infection. The authors proposed Man Tsuey Tse that simultaneous vaccination with these three antigens could produce ORIGINAL RESEARCH PAPER Aagaard, C. et al. multistage effects, by enabling the A multistage tuberculosis vaccine that confers efficient protection before and after exposure. immune system to mount a response Nature Med. 17, 189–194 (2011) to both the early and late phases of TB.