Safety, immunogenicity, and efficacy of the candidate tuberculosis vaccine MVA85A in healthy adults infected with HIV-1: a randomised, placebo-controlled, phase 2 trial

Ndiaye, B; Thienemann, Friedrich; Ota, Martin O. C.; Landry, Bernard; Camara, Makhtar; Dièye, Siry; Diéye, Tandakha Ndiaye; Esmail, Hanif; Goliath, René; Huygen, Kris; January, Vanessa; Ndiaye, Ibrahima; Oni, Tolu; Raine, Michael; Romano, Márta; Satti, Iman; Sutton, Sharon E.; Thiam, Alioune Badara; Wilkinson, Katalin A.; Mboup, Souleymane; Wilkinson, Robert J.; McShane, Helen

doi:10.1016/s2213-2600(15)00037-5

Cited by 131 publications

(130 citation statements)

References 26 publications

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“…53,54 However, an underpowered Phase II trial of MVA85A in adults infected with HIV revealed that MVA85A showed no trend in efficacy against M. tuberculosis infection or disease. 55 Similar results were observed in another Phase IIb trial of MVA85A in infants conducted in South Africa. Healthy infants aged 4 to 6 months who had been previously inoculated with BCG shortly after birth received a dose of MVA85A or a placebo between 4 and 6 months of age.…”

Section: Mva85a(aeras-485)supporting

confidence: 78%

Current status of new tuberculosis vaccine in children

Pang

Zhao

Cohen³

et al. 2016

Human Vaccines & Immunotherapeutics

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Pediatric tuberculosis contributes significantly to the burden of TB disease worldwide. In order to achieve the goal of eliminating TB by 2050, an effective TB vaccine is urgently needed to prevent TB transmission in children. BCG vaccination can protect children from the severe types of TB such as TB meningitis and miliary TB, while its efficacy against pediatric pulmonary TB ranged from no protection to very high protection. In recent decades, multiple new vaccine candidates have been developed, and shown encouraging safety and immunogenicity in the preclinical experiments. However, the limited data on protective efficacy in infants evaluated by clinical trials has been disappointing, an example being MVA85A. To date, no vaccine has been shown to be clinically safer and more effective than the presently licensed BCG vaccine. Hence, before a new vaccine is developed with more promising efficacy, we must reconsider how to better use the current BCG vaccine to maximize its effectiveness in children.

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Section: Mva85a(aeras-485)supporting

confidence: 78%

Current status of new tuberculosis vaccine in children

Pang

Zhao

Cohen³

et al. 2016

Human Vaccines & Immunotherapeutics

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“…Immunological responses considered critical for long-term mycobacterial control have focused on conventional T cell responses directed at peptide antigens presented by major histocompatibility complex (MHC) I and II, ultimately leading to secretion of anti-microbial cytokines, including TNF-α and IFN-γ (3,4). A number of subunit vaccines based on immunogenic peptides have been developed, some of which have been evaluated in clinical trials, but results to date have not been encouraging (5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

CD1b-restricted GEM T cell responses are modulated byMycobacterium tuberculosismycolic acid meromycolate chains

Chancellor

Tocheva

Cave-Ayland

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Tuberculosis, caused by Mycobacterium tuberculosis, remains a major human pandemic. Germline-encoded mycolyl lipid-reactive (GEM) T cells are donor-unrestricted and recognize CD1b-presented mycobacterial mycolates. However, the molecular requirements governing mycolate antigenicity for the GEM T cell receptor (TCR) remain poorly understood. Here, we demonstrate CD1b expression in tuberculosis granulomas and reveal a central role for meromycolate chains in influencing GEM-TCR activity. Meromycolate fine structure influences T cell responses in TB-exposed individuals, and meromycolate alterations modulate functional responses by GEM-TCRs. Computational simulations suggest that meromycolate chain dynamics regulate mycolate head group movement, thereby modulating GEM-TCR activity. Our findings have significant implications for the design of future vaccines that target GEM T cells. Mycobaterium tuberculosis | GEM T cells | CD1b | Mycolate lipids |

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“…Therefore, any vaccines or vaccination strategies that are able to elicit the mucosal immune response may enhance the efficacy of protection against Mtb infection. Great efforts have been made to improve the protective efficacy of TB vaccines and various types of vaccine candidates or vectors have been developed, including the recombinant BCG (rBCG), DNA vaccines, nanoparticle vaccines, recombinant modified vaccinia virus Ankara and recombinant adenoviral-based vaccines (12,15,32,59,60). Among them, the adenoviral-based TB vaccines have gained increased attention, as they were first evaluated as mucosal TB vaccine candidates (15).…”

Section: Discussionmentioning

confidence: 99%

Prime-boost vaccination with Bacillus Calmette Guerin and a recombinant adenovirus co-expressing CFP10, ESAT6, Ag85A and Ag85B of Mycobacterium tuberculosis induces robust antigen-specific immune responses in mice

Deng

et al. 2015

Molecular Medicine Reports

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Abstract. Tuberculosis (TB) remains to be a prevalent health issue worldwide. At present, Mycobacterium bovis Bacillus Calmette Guerin (BCG) is the singular anti-TB vaccine available for the prevention of disease in humans; however, this vaccine only provides limited protection against Mycobacterium tuberculosis (Mtb) infection. Therefore, the development of alternative vaccines and strategies for increasing the efficacy of vaccination against TB are urgently required. The present study aimed to evaluate the ability of a recombinant adenoviral vector (Ad5-CEAB) co-expressing 10-kDa culture filtrate protein, 6-kDa early-secreted antigenic target, antigen 85 (Ag85) A and Ag85B of Mtb to boost immune responses following primary vaccination with BCG in mice. The mice were first subcutaneously primed with BCG and boosted with two doses of Ad5-CEAB via an intranasal route. The immunological effects of Ad5-CEAB boosted mice primed with BCG were then evaluated using a series of immunological indexes. The results demonstrated that the prime-boost strategy induced a potent antigen-specific immune response, which was primarily characterized by an enhanced T cell response and increased production of cytokines, including interferon-γ, tumor necrosis factor-α and interleukin-2, in mice. In addition, this vaccination strategy was demonstrated to have an elevated humoral response with increased concentrations of antigen-specific bronchoalveolar lavage secretory immunoglobulin (Ig)A and serum IgG in mice compared with those primed with BCG alone. These data suggested that the regimen of subcutaneous BCG prime and mucosal Ad5-CEAB boost was a novel strategy for inducing a broad range of antigen-specific immune responses to Mtb antigens in vivo, which may provide a promising strategy for further development of adenoviral-based vaccine against Mtb infection. IntroductionTuberculosis (TB) is one of the most prevalent infectious diseases worldwide, accounting for ~1.4 million mortalities and 8.7 million novel cases annually, which occurs as a results of Mycobacterium tuberculosis (Mtb) infection (1). Due to Mtb reactivation at a latent state in immunocompromised individuals, slow progress in dealing with drug-resistant Mtb infection and the co-infection of Mtb with human immunodeficiency virus, the global burden of TB remains high, particularly in developing countries (2,3).Effective vaccines are of key importance in ending the global TB epidemic (1). However, a consistently effective vaccine is not currently available. The only available TB vaccine, attenuated Mycobacterium bovis Bacillus Calmette Guerin (BCG) has made a marked contribution to Mtb infection control, especially in juvenile population and newborns (4). However, BCG does not provide effective protection for all age groups, particularly in adults; its protective efficacy is highly varied from different trials, with certain studies observing negative effects associated with BCG revaccination (0-80%) (5,6). Therefore, the development of more effective vaccines or feasible...

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Safety, immunogenicity, and efficacy of the candidate tuberculosis vaccine MVA85A in healthy adults infected with HIV-1: a randomised, placebo-controlled, phase 2 trial

Cited by 131 publications

References 26 publications

Current status of new tuberculosis vaccine in children

Current status of new tuberculosis vaccine in children

CD1b-restricted GEM T cell responses are modulated byMycobacterium tuberculosismycolic acid meromycolate chains

Prime-boost vaccination with Bacillus Calmette Guerin and a recombinant adenovirus co-expressing CFP10, ESAT6, Ag85A and Ag85B of Mycobacterium tuberculosis induces robust antigen-specific immune responses in mice

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