ChAdOx1.85A ChAdOx1.85A is a live-attenuated chimpanzee adenovirus (ChAd) viral vector that expresses Ag85A [10]. The potential advantage of the ChAd vector compared with vectors derived from commonly circulating human adenoviruses such as Ad5 is that humans are less likely to have had prior exposure, which can be associated with vector-specific neutralising antibodies that limit vaccine-induced immune responses [44]. Animal studies have shown that ChAdOx1.85A evokes both humoral and cell-mediated immune responses when administered either systemically or via the mucosa [45, 46]. Phase 1 trials have shown that ChAdOx1.85A is well tolerated and induces a strong humoral and cell-mediated immune response when administered via the nasal or sublingual route to humans [11, 47]. A phase 2a trial of ChAdOx1.85A dose escalation, followed by ChAdOx1.85A–MVA85A boost, with BCG revaccination as a comparator, has completed enrolment (ClinicalTrials.gov identifier NCT03681860). A previous phase 2b trial of MVA85A, a modified vaccinia Ankara expressing Ag85A, in BCG-vaccinated infants showed no efficacy for boost vaccination against TB. TB/FLU-04L TB/FLU-04L vaccine is a live-attenuated influenza virus strain, A/Puerto Rico/8/34 H1N1, that expresses the mycobacterial antigens Ag85A and ESAT-6 (6 kDa early secreted antigenic target), which have been shown to evoke strong cell-mediated immune responses [48]. TB/FLU-04L was shown to be immunogenic when administered via the nasal mucosa in animal studies, with a higher T-cell response when primed with BCG vaccine. A small phase 1 study was completed to assess the safety and immunogenicity of two doses of TB/FLU-04L in BCG-vaccinated, IGRA-negative adults (ClinicalTrials.gov identifier NCT02501421). Protein adjuvant candidate vaccines Five protein-subunit vaccines are in phase 2a–3 trials. H56:IC31 H56:IC31 is a fusion protein consisting of three M. tuberculosis antigens, Ag85B, ESAT-6 and Rv2660c, formulated with a T-helper type 1 cell (Th1)-stimulating adjuvant, IC31 [49]. H56:IC31 was designed as both a preventive and a therapeutic vaccine. Three completed clinical trials investigated the safety and immunogenicity of H56:IC31 in adolescents and adults without M. tuberculosis sensitisation, and in M. tuberculosis-sensitised adults, defined by IGRA status. A total of 246 participants have been enrolled in all studies, of whom 158 were M. tuberculosis unsensitised, 49 were M. tuberculosis sensitised [13–15], and 39 were TB patients enrolled in Norway who were undergoing TB treatment [16]. These studies suggest that H56:IC31 is safe and immunogenic in BCG-primed individuals with or without M. tuberculosis sensitisation, as well as in individuals undergoing TB treatment. H56:IC31 is currently being evaluated in a phase 2b trial for efficacy in preventing TB recurrence (relapse or re-infection) in 831 HIV-negative patients who have been successfully treated for drug-susceptible TB (DS-TB) (ClinicalTrials.gov identifier NCT03512249). Follow-up was completed in March 2023 and the results, which may green-light expansion into larger preventive and/or therapeutic efficacy trials, are awaited. ID93/GLA-SE or QTP101 ID93/GLA-SE vaccine is a recombinant protein comprising four M. tuberculosis antigens, Rv2608, Rv3620, Rv1813 and Rv3619, formulated with GLA-SE adjuvant, a Toll-like receptor 4 agonist in a stable oil-in-water emulsion. ID93/GLA-SE has been shown to be safe and immunogenic in HIV-negative individuals with or without M. tuberculosis sensitisation, defined by IGRA status, and in TB patients who have successfully completed treatment for https://doi.org/10.1183/2312508X.10024922 167 RECENT ADVANCES IN VACCINES |A.K.K. LUABEYA ET AL.