Novel prophylactic and therapeutic vaccine against tuberculosis

Okada, Masaji; Kita, Yoko; Nakajima, Takeshi; Kanamaru, Noriko; Hashimoto, Satomi; Nagasawa, T; Kaneda, Yasufumi; Yoshida, Shigeto; Nishida, Yasuko; Nakatani, Hitoshi; Takao, Katsuyuki; Kishigami, Chie; Inoue, Yoshikazu; Matsumoto, Makoto; McMurray, David N.; Cruz, Eduardo Canteiro; Tan, Esterlina V.; Abalos, Rodolfo M.; Burgos, Jasmin; Saunderson, Paul; Sakatani, Mitsunori

doi:10.1016/j.vaccine.2009.01.064

Cited by 38 publications

(60 citation statements)

References 8 publications

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“…New technologies targeted at the vast reservoir of latently infected people would be of great benefit, particularly if combined with one or more of the novel technologies in the current pipeline. The 2 combinations, a 2-month treatment regimen combined with mass latent therapy and mass vaccination with pre-exposure vaccine combined with postexposure vaccine administered to latently infected people (15), provide similarly powerful reductions in TB mortality, preventing 73% and 75% of deaths, respectively. Our approach differs from previous models in being based on the actual targeted or expected efficacies of the technologies under development.…”

Section: Discussionmentioning

confidence: 99%

“…A similar relative shortening is expected for other baseline durations between onset of illness and detection. In the Southeast Asia region, the relative shortenings for the novel diagnostics were computed based on 15.4 months of average duration from onset of disease to detection in smear-positive cases and 23.0 months in smear-negative cases (15). In a sensitivity analysis, we varied the proportionate reduction in average duration of infectiousness from 0 to 1.0.…”

Section: Novel Portfolio Interventionsmentioning

confidence: 99%

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Epidemiological benefits of more-effective tuberculosis vaccines, drugs, and diagnostics

Abu‐Raddad

Sabatelli

Achterberg

et al. 2009

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

325

303

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The Bill and Melinda Gates Foundation supports an ambitious portfolio of novel vaccines, drug regimens, and diagnostic tools for tuberculosis (TB). We elicited the expected efficacies and improvements of the novel interventions in discussions with the foundations managing their development. Using an age-structured mathematical model of TB, we explored the potential benefits of novel interventions under development and those not yet in the portfolio, focusing on the WHO Southeast Asia region. Neonatal vaccination with the portfolio vaccine decreases TB incidence by 39% to 52% by 2050. Drug regimens that shorten treatment duration and are efficacious against drug-resistant strains reduce incidence by 10 -27%. New diagnostics reduce incidence by 13-42%. A triple combination of a portfolio vaccine, drug regimen, and diagnostics reduces incidence by 71%. A short mass vaccination catch-up campaign, not yet in the portfolio, to augment the triple combination, accelerates the decrease, preventing >30% more cases by 2050 than just the triple combination. New vaccines and drug regimens targeted at the vast reservoir of latently infected people, not in the portfolio, would reduce incidence by 37% and 82%, respectively. The combination of preventive latent therapy and a 2-month drug treatment regimen reduces incidence by 94%. Novel technologies in the pipeline would achieve substantial reductions in TB incidence, but not the Stop TB Partnership target for elimination. Elimination will require new delivery strategies, such as mass vaccination campaigns, and new products targeted at latently infected people. latent infection ͉ novel interventions ͉ transmission model ͉ latent therapy T he Bill and Melinda Gates Foundation (BMGF) supports an ambitious portfolio of novel vaccines, treatment regimens, and diagnostic tools for tuberculosis (TB). Funded by BMFG and other sources, the Aeras Global TB Vaccine Foundation oversees vaccine development (1), the TB Alliance seeks novel drug regimens (2), and the Foundation for Innovative New Diagnostics (FIND) looks for new diagnostic tools (3). The current cornerstone of TB intervention is directly observed short-course therapy (DOTS), lasting generally 6 months and prone to dropout (4). DOTS is currently implemented in the 184 countries where 99% of all estimated TB cases occurred and 93% of the world population lived in 2006 (5). Cases are passively ascertained. Sputum smear light microscopy has been the mainstay of TB diagnosis for more than a century, but has important limitations (3). Delays between the patient visit to the clinic and diagnosis often lead to delays in treatment. Neonatal vaccination with bacillus Calmette-Guérin (BCG) vaccine is part of the expanded program of immunization in many countries, but its efficacy against pulmonary TB is poor (1). Despite these efforts, in large parts of Asia, Africa, Eastern Europe, and Latin America, incidence remains 2 orders of magnitude (5) above the Stop TB Partnership goal to eliminate TB as a public health problem, defined as Ͻ1 ...

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Section: Discussionmentioning

confidence: 99%

Section: Novel Portfolio Interventionsmentioning

confidence: 99%

Epidemiological benefits of more-effective tuberculosis vaccines, drugs, and diagnostics

Abu‐Raddad

Sabatelli

Achterberg

et al. 2009

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

325

303

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“…Previous studies in which TB vaccine candidates have been evaluated for efficacy in rhesus macaques have ended at a fixed point, 8 to 17 weeks after either aerosol (1,2,3,14,26) or intratracheal (15, 31) challenge. Longer-term studies of vaccine efficacy with postchallenge investigation periods in excess of 16 weeks have been conducted with cynomolgus macaques (22,23,25). In the latter studies, survival after challenge has provided a readout of vaccine efficacy, although only one of the four efficacy studies reported (21) was sufficiently long to allow the entire unvaccinated group to progress to end-stage disease, i.e., not survive the challenge.…”

Section: Discussionmentioning

confidence: 99%

Establishment of an Aerosol Challenge Model of Tuberculosis in Rhesus Macaques and an Evaluation of Endpoints for Vaccine Testing

Sharpe

McShane

Dennis

et al. 2010

Clin Vaccine Immunol

123

167

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The establishment of an aerosol challenge model in nonhuman primates (NHPs) for the testing of vaccines against Mycobacterium tuberculosis would assist the global effort to optimize novel vaccination strategies. The endpoints used in preclinical challenge studies to identify measures of disease burden need to be accurate and sensitive enough to distinguish subtle differences and benefits afforded by different tuberculosis (TB) vaccine regimens when group sizes are inevitably small. This study sought to assess clinical and nonclinical endpoints as potentially sensitive measures of disease burden in a challenge study with rhesus macaques by using a new protocol of aerosol administration of M. tuberculosis. Immunological and clinical readouts were assessed for utility in vaccine evaluation studies. This is the first example of TB vaccine evaluation with rhesus macaques where long-term survival was one of the primary endpoints. However, we found that in NHP vaccine efficacy studies with maximum group sizes of six animals, survival did not provide a valuable endpoint. Two approaches used in human clinical trials for the evaluation of the gamma interferon (IFN-␥) response to vaccination (enzyme-linked immunospot [ELISpot] assay and enzyme-linked immunosorbent assay [ELISA])were included in this study. The IFN-␥ profiles induced following vaccination were found not to correlate with protection, nor did the level of purified protein derivative (PPD)-specific proliferation. The only readout to reliably distinguish vaccinated and unvaccinated NHPs was the determination of lung lesion burden using magnetic resonance (MR) imaging combined with stereology at the end of the study. Therefore, the currently proposed key markers were not shown to correlate with protection, and only imaging offered a potentially reliable correlate.Tuberculosis (TB) is a reemerging infectious disease and is responsible for nearly 2 million deaths and 9 million new cases each year (36). The global TB pandemic has been exacerbated by the emergence of drug-resistant strains of Mycobacterium tuberculosis, which render treatment less effective, and by the HIV epidemic, where coinfection with HIV greatly increases the risk of reactivation of latent TB and susceptibility to active TB disease.The most effective means of controlling this global epidemic would be by prophylactic immunization. Mycobacterium bovis bacille Calmette-Guérin (BCG), the only licensed TB vaccine, is administered to neonates in high-risk populations as part of the WHO Expanded Programme on Immunization. BCG consistently protects against TB meningitis and disseminated TB in childhood (27,30), but its efficacy wanes with time, and it affords only variable protection against pulmonary disease (10). A new, more effective TB vaccine is a major global health priority and is an important part of the WHO STOP TB partnership strategy.A large international effort is under way to develop a more effective vaccine. The leading TB vaccine development strategy involves vaccination with BCG followe...

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“…While a number of vaccine efficacy studies have been published using the high-dose cynomolgus or rhesus macaque models of infection (8,37,41,42), to our knowledge this is the first vaccine trial in which both low- and high-dose M. tuberculosis challenges were performed. The H56 booster vaccine gave similar outcomes in the two models, and in particular very low levels of the inflammation marker ESR and low infection-driven responses to CFP10 were striking observations in both experiments and indicated efficient control of bacterial replication.…”

Section: Figurementioning

confidence: 99%

The multistage vaccine H56 boosts the effects of BCG to protect cynomolgus macaques against active tuberculosis and reactivation of latent Mycobacterium tuberculosis infection

Lin¹,

Dietrich²,

Tan³

et al. 2012

J. Clin. Invest.

220

198

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Novel prophylactic and therapeutic vaccine against tuberculosis

Cited by 38 publications

References 8 publications

Epidemiological benefits of more-effective tuberculosis vaccines, drugs, and diagnostics

Epidemiological benefits of more-effective tuberculosis vaccines, drugs, and diagnostics

Establishment of an Aerosol Challenge Model of Tuberculosis in Rhesus Macaques and an Evaluation of Endpoints for Vaccine Testing

The multistage vaccine H56 boosts the effects of BCG to protect cynomolgus macaques against active tuberculosis and reactivation of latent Mycobacterium tuberculosis infection

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