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Advancing mRNA technologies for therapies and vaccines: An African context.

ABSTRACT: Synthetic mRNA technologies represent a versatile platform that can be used to develop advanced drug products. The remarkable speed with which vaccine development programs designed and manufactured safe and effective COVID-19 vaccines has rekindled interest in mRNA technology, particularly for future pandemic preparedness. Although recent R&D has focused largely on advancing mRNA vaccines and large-scale manufacturing capabilities, the technology has been used to develop various immunotherapies, gene editing strategies, and protein replacement therapies. Within the mRNA technologies toolbox lie several platforms, design principles, and components that can be adapted to modulate immunogenicity, stability, in situ expression, and delivery. For example, incorporating modified nucleotides into conventional mRNA transcripts can reduce innate immune responses and improve in situ translation. Alternatively, self-amplifying RNA may enhance vaccine-mediated immunity by increasing antigen expression. This review will highlight recent advances in the field of synthetic mRNA therapies and vaccines, and discuss the ongoing global efforts aimed at reducing vaccine inequity by establishing mRNA manufacturing capacity within Africa and other low- and middle-income countries.

SUBMITTER: Kairuz D

PROVIDER: S-EPMC9637871 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Advancing mRNA technologies for therapies and vaccines: An African context.

Kairuz Dylan D Samudh Nazia N Ely Abdullah A Arbuthnot Patrick P Bloom Kristie K

Frontiers in immunology 20221024

Synthetic mRNA technologies represent a versatile platform that can be used to develop advanced drug products. The remarkable speed with which vaccine development programs designed and manufactured safe and effective COVID-19 vaccines has rekindled interest in mRNA technology, particularly for future pandemic preparedness. Although recent R&D has focused largely on advancing mRNA vaccines and large-scale manufacturing capabilities, the technology has been used to develop various immunotherapies, ...[more]

PMID: 36353641

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Project description:The World Health Organization (WHO) recently put forth a Global Strategy on Digital Health 2020-2025 with several countries having already achieved key milestones. We aimed to understand whether and how digital health technologies (DHTs) are absorbed in Africa, tracking Ethiopia as a key node. We conducted a systematic review, searching PubMed-MEDLINE, Embase, ScienceDirect, African Journals Online, Cochrane Central Registry of Controlled Trials, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform databases from inception to 02 February 2021 for studies of any design that investigated the potential of DHTs in clinical or public health practices in Ethiopia. This review was registered with PROSPERO ( CRD42021240645 ) and it was designed to inform our ongoing DHT-enabled randomized controlled trial (RCT) (ClinicalTrials.gov ID: NCT04216420 ). We found 27,493 potentially relevant citations, among which 52 studies met the inclusion criteria, comprising a total of 596,128 patients, healthy individuals, and healthcare professionals. The studies involved six DHTs: mHealth (29 studies, 574,649 participants); electronic health records (13 studies, 4534 participants); telemedicine (4 studies, 465 participants); cloud-based application (2 studies, 2382 participants); information communication technology (3 studies, 681 participants), and artificial intelligence (1 study, 13,417 participants). The studies targeted six health conditions: maternal and child health (15), infectious diseases (14), non-communicable diseases (3), dermatitis (1), surgery (4), and general health conditions (15). The outcomes of interest were feasibility, usability, willingness or readiness, effectiveness, quality improvement, and knowledge or attitude toward DHTs. Five studies involved RCTs. The analysis showed that although DHTs are a relatively recent phenomenon in Ethiopia, their potential harnessing clinical and public health practices are highly visible. Their adoption and implementation in full capacity require more training, access to better devices such as smartphones, and infrastructure. DHTs hold much promise tackling major clinical and public health backlogs and strengthening the healthcare ecosystem in Ethiopia. More RCTs are needed on emerging DHTs including artificial intelligence, big data, cloud, cybersecurity, telemedicine, and wearable devices to provide robust evidence of their potential use in such settings and to materialize the WHO's Global Strategy on Digital Health.

Project description:BackgroundDevelopment of new, effective, and affordable tuberculosis (TB) therapies has been identified as a critical priority for global TB control. As new candidates emerge from the global TB drug pipeline, the potential impacts of novel, shorter regimens on TB incidence and mortality have not yet been examined.Methods and findingsWe used a mathematical model of TB to evaluate the expected benefits of shortening the duration of effective chemotherapy for active pulmonary TB. First, we considered general relationships between treatment duration and TB dynamics. Next, as a specific example, we calibrated the model to reflect the current situation in the South-East Asia region. We found that even with continued and rapid progress in scaling up the World Health Organization's DOTS strategy of directly observed, short-course chemotherapy, the benefits of reducing treatment duration would be substantial. Compared to a baseline of continuing DOTS coverage at current levels, and with currently available tools, a 2-mo regimen introduced by 2012 could prevent around 20% (range 13%-28%) of new cases and 25% (range 19%-29%) of TB deaths in South-East Asia between 2012 and 2030. If effective treatment with existing drugs expands rapidly, overall incremental benefits of shorter regimens would be lower, but would remain considerable (13% [range 8%-19%] and 19% [range 15%-23%] reductions in incidence and mortality, respectively, between 2012 and 2030). A ten-year delay in the introduction of new drugs would erase nearly three-fourths of the total expected benefits in this region through 2030.ConclusionsThe introduction of new, shorter treatment regimens could dramatically accelerate the reductions in TB incidence and mortality that are expected under current regimens-with up to 2- or 3-fold increases in rates of decline if shorter regimens are accompanied by enhanced case detection. Continued progress in reducing the global TB burden will require a balanced approach to pursuing new technologies while promoting wider implementation of proven strategies.

Dataset Information

Advancing mRNA technologies for therapies and vaccines: An African context.

Publications

Advancing mRNA technologies for therapies and vaccines: An African context.

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