DAR-901 vaccine for the prevention of infection with Mycobacterium tuberculosis among BCG-immunized adolescents in Tanzania: A randomized controlled, double-blind phase 2b trial

Munseri, Patricia; Said, Jamila; Amour, Maryam; Magohe, Albert; Matee, Mecky; Rees, Christiaan A.; MacKenzie, Todd A.; Tvaroha, Susan; Bailey‐Kellogg, Chris; Maro, Isaac; Wieland-Alter, Wendy; Adams, Lisa V.; Horsburgh, C. Robert; Nakamura, Keiko; Arbeit, Robert D.; Pallangyo, Kisali; Reyn, C. Fordham von

doi:10.1016/j.vaccine.2020.09.055

Cited by 36 publications

(27 citation statements)

References 20 publications

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“…No vaccine has yet been launched for HIV, and the existing vaccine for TB, Bacillus Calmette-Gu erin (BCG), is sub-optimal and does not interrupt transmission. A number of novel TB vaccine candidates are in the pipeline [39], such as DAR901 [40] and M72/AS01E [41], the latter of which provides 54% protection against pulmonary TB disease in infected adults, and is the first moderately effective vaccine against TB disease in adults to be developed in almost 100 years. Given the slow pace of vaccine development for TB and HIV, it is also hoped that the successes, in such a short space of time, for the development of COVID-19 vaccines prove that with sufficient political will and resources, vaccine development for other infectious diseases can be much more efficient.…”

Section: Discussionmentioning

confidence: 99%

Turning threats into opportunities: how to implement and advance quality TB services for people with HIV during the COVID‐19 pandemic and beyond

Roberts

Sahu²,

Malar³

et al. 2021

J. Intern. AIDS Soc.

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Introduction: Until COVID-19, tuberculosis (TB) was the leading infectious disease killer globally, disproportionally affecting people with HIV. The COVID-19 pandemic is threatening the gains made in the fight against both diseases. Discussion: Although crucial guidance has been released on how to maintain TB and HIV services during the pandemic, it is acknowledged that what was considered normal service pre-pandemic needs to improve to ensure that we rebuild person-centred, inclusive and quality healthcare services. The threat that the pandemic may reverse gains in the response to TB and HIV may be turned into an opportunity by pivoting to using proven differentiated service delivery approaches and innovative technologies that can be used to maintain care during the pandemic and accelerate improved service delivery in the long term. Models of care should be convenient, supportive and sufficiently differentiated to avoid burdensome clinic visits for medication pick-ups or directly observed treatments. Additionally, the pandemic has highlighted the chronic and short-sighted lack of investment in health systems and the need to prioritize research and development to close the gaps in TB diagnosis, treatment and prevention, especially for children and people with HIV. Most importantly, TB-affected communities and civil society must be supported to lead the planning, implementation and monitoring of TB and HIV services, especially in the time of COVID-19 where services have been disrupted, and to report on legal, policy and gender-related barriers to access experienced by affected people. This will help to ensure that TB services are held accountable by affected communities for delivering equitable access to quality, affordable and non-discriminatory services during and beyond the pandemic. Conclusions: Successfully reaching the related targets of ending TB and AIDS as public health threats by 2030 requires rebuilding of stronger, more inclusive health systems by advancing equitable access to quality TB services, including for people with HIV, both during and after the COVID-19 pandemic. Moreover, services must be rights-based, community-led and community-based, to ensure that no one is left behind.

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Section: Discussionmentioning

confidence: 99%

Turning threats into opportunities: how to implement and advance quality TB services for people with HIV during the COVID‐19 pandemic and beyond

Roberts

Sahu²,

Malar³

et al. 2021

J. Intern. AIDS Soc.

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“…C. Fordham von Reyn (Dartmouth Geisel School of Medicine, USA) presented results from the phase 2b 1:1 randomized, placebo controlled trial of DAR-901 [NCT02712424], an inactivated M. obuense (non-tuberculous mycobacterium), for prevention of infection in 650 BCG vaccinated, IGRA-negative Tanzanian adolescents [19] . Participants were followed over three years with five IGRA tests, and the primary endpoint was defined as IGRA conversion.…”

Section: Clinical Research For Tb Vaccinesmentioning

confidence: 99%

Meeting report: Virtual Global Forum on Tuberculosis Vaccines, 20–22 April 2021

Suliman¹,

Pelzer²,

Shaku³

et al. 2021

Vaccine

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The Global Forum on Tuberculosis (TB) Vaccines was held virtually from 20 to 22 April 2021, marking its 20 th anniversary. The Global Forum on TB Vaccines is the world's largest gathering of stakeholders striving to develop new vaccines to prevent TB. The program included more than 60 speakers in 11 scientific sessions, panel discussions, and workshops. It provided an overview of the state of the field, and an opportunity to share the latest research findings, as well as new and innovative approaches to TB vaccine research and development (R&D). This year, it was held against the backdrop of the COVID-19 pandemic and convened researchers, developers, funders, and other stakeholders remotely to discuss opportunities and challenges for TB vaccine R&D in these unprecedented times.

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“…A candidate from the same master cell bank, DAR‐901, has since been adapted for broth‐based production, and recently completed a phase IIb trial. [28,29]. This study measured the prevention of Mtb infection in 667 BCG‐vaccinated, HIV‐negative and IGRA‐negative Tanzanian adolescents.…”

Section: Candidates In Clinical Trialsmentioning

confidence: 99%

“…This study measured the prevention of Mtb infection in 667 BCG‐vaccinated, HIV‐negative and IGRA‐negative Tanzanian adolescents. A three‐dose series of DAR‐901 was safe and well‐tolerated, but did not show any differences in either primary (IGRA conversion) or secondary (sustained IGRA conversion) end‐points [30]. [Correction added on 22 January 2021, after first online publication: this paragraph has been amended.…”

Section: Candidates In Clinical Trialsmentioning

confidence: 99%

“…As the trial was not primarily designed to study this end‐point, a larger trial is required to further investigate this result. A BCG revaccination trial of 1800 BCG‐vaccinated IGRA‐negative children and adolescents (age 10–18) has been initiated in South Africa, with a primary outcome of prevention of sustained IGRA conversion at 3 and 6 months [30]. Results are anticipated in 2025.…”

Section: Candidates In Clinical Trialsmentioning

confidence: 99%

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New tuberculosis vaccines: advances in clinical development and modelling

et al. 2020

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Tuberculosis remains a major source of morbidity and mortality worldwide, with 10 million cases and 1.5 million deaths in 2018. Achieving ‘End TB’ prevention and care goals by 2035 will likely require a new tuberculosis vaccine. The tuberculosis vaccine development pipeline has seen encouraging progress; however, questions around their population impact and implementation remain. Mathematical modelling investigates these questions to inform vaccine development and deployment strategies. We provide an update on the current vaccine development pipeline, and a systematic literature review of mathematical modelling of the epidemiological impact of new tuberculosis vaccines. Fourteen prophylactic tuberculosis vaccine candidates are currently in clinical trials. Two candidates have shown promise in phase II proof‐of‐concept efficacy trials: M72/AS01E demonstrated 49.7% (95% CI; 2.1, 74.2) protection against tuberculosis disease, and BCG revaccination demonstrated 45.4% (95% CI; 6.4, 68.1) protection against sustained Mycobacterium tuberculosis infection. Since the last modelling review, new studies have investigated the epidemiological impact of differential vaccine characteristics, age targeting and spatial/risk group targeting. Critical research priorities for M72/AS01E include completing the currently in‐design trial, powered to improve the precision of efficacy estimates, include uninfected populations and further assess safety and immunogenicity in HIV‐infected people. For BCG revaccination, the priority is completing the ongoing confirmation of efficacy trial. Critical modelling gaps remain on the full value proposition of vaccines, comparisons with other interventions and more realistic implementation strategies. Using carefully designed trials and modelling, we must prepare for success, to ensure that new vaccines will be promptly received by those most in need.

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DAR-901 vaccine for the prevention of infection with Mycobacterium tuberculosis among BCG-immunized adolescents in Tanzania: A randomized controlled, double-blind phase 2b trial

Cited by 36 publications

References 20 publications

Turning threats into opportunities: how to implement and advance quality TB services for people with HIV during the COVID‐19 pandemic and beyond

Turning threats into opportunities: how to implement and advance quality TB services for people with HIV during the COVID‐19 pandemic and beyond

Meeting report: Virtual Global Forum on Tuberculosis Vaccines, 20–22 April 2021

New tuberculosis vaccines: advances in clinical development and modelling

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