COVID-19 and other adult vaccines can drive global disease prevention
2022; Elsevier BV; Volume: 401; Issue: 10370 Linguagem: Inglês
10.1016/s0140-6736(22)02084-0
ISSN1474-547X
AutoresDavid B. Agus, Aurélia Nguyen, Amadou Alpha Sall, John I. Bell,
Tópico(s)Respiratory viral infections research
ResumoThe COVID-19 pandemic has led to a renewed recognition of the importance of disease prevention and public health globally. The progress in COVID-19 vaccine technology is a small portion of the pipeline of new vaccines and injectable therapies that could prevent leading causes of premature death and disability. This pipeline comes from decades of investment by governments and work by pharmaceutical companies, academic researchers, and new entrants in the field. The urgent need for new COVID-19 vaccines has also accelerated developments in this pipeline. Mirroring success during the past 50 years with the Expanded Programme on Immunization for children, global life course vaccination and other preventive strategies that use these products would strengthen health systems globally and have a major impact on disease prevention. In the adult vaccine space, new products at multiple stages of preclinical and clinical development for coronaviruses, influenza, and respiratory syncytial virus (RSV) are expected to emerge in the coming months and years.1Dolgin E Pan-coronavirus vaccine pipeline takes form 2022.Nat Rev Drug Discov. 2022; 21: 324-326Crossref PubMed Scopus (33) Google Scholar, 2Wei C-J Crank MC Shiver J Graham BS Mascola JR Nabel GJ Next-generation influenza vaccines: opportunities and challenges.Nat Rev Drug Discov. 2020; 19: 239-252Crossref PubMed Scopus (138) Google Scholar, 3Abbasi J RSV vaccines, finally within reach, could prevent tens of thousands of yearly deaths.JAMA. 2022; 327: 204-206Crossref PubMed Scopus (7) Google Scholar These could become staple products for reducing adult disease burden, particularly in winter. Although the global burden of these diseases is difficult to estimate due to insufficient data in many countries, it is likely to be considerable. For example, estimates suggest that influenza causes 389 000 deaths annually, with the majority of cases in southeast Asia, the Western Pacific region, and sub-Saharan Africa, and that at least 14 000 hospital-based deaths are caused by RSV acute respiratory infection globally, although this is likely to be an underestimation of total deaths from RSV.4Paget J Spreeuwenberg P Charu V et al.Global mortality associated with seasonal influenza epidemics: new burden estimates and predictors from the GLaMOR Project.J Glob Health. 2019; 9020421Crossref PubMed Scopus (292) Google Scholar, 5Shi T Denouel A Tietjen AK et al.Global disease burden estimates of respiratory syncytial virus–associated acute respiratory infection in older adults in 2015: a systematic review and meta-analysis.J Infect Dis. 2019; 222: S577-S583Google Scholar As durability of vaccine-induced immune response is likely to remain a challenge, an annual immunisation cycle for these infectious diseases is possible and would have real population-level health benefits. If COVID-19 and influenza booster doses become the mainstay of annual adult immunisation programmes, other innovative products could be used alongside them. Vaccines in development for tuberculosis and malaria, for example, have promising phase 2 data, with efficacy of up to 50% against tuberculosis and 80% against malaria in children.6Tait DR Hatherill M Van Der Meeren O et al.Final analysis of a trial of M72/AS01E vaccine to prevent tuberculosis.New Engl J Med. 2019; 381: 2429-2439Crossref PubMed Scopus (231) Google Scholar, 7Datoo MS Natama MH Somé A et al.Efficacy and immunogenicity of R21/Matrix-M vaccine against clinical malaria after 2 years' follow-up in children in Burkina Faso: a phase 1/2b randomised controlled trial.Lancet Infect Dis. 2022; (published online Sept 7.)https://doi.org/10.1016/S1473-3099(22)00442-XSummary Full Text Full Text PDF PubMed Scopus (31) Google Scholar Although malaria burden in children is substantial, evidence suggests that its burden in adults is underestimated,8Dhingra N Jha P Sharma VP et al.Adult and child malaria mortality in India: a nationally representative mortality survey.Lancet. 2010; 376: 1768-1774Summary Full Text Full Text PDF PubMed Scopus (206) Google Scholar and a malaria vaccine with encouraging phase 2 data is now being tested in adults (NCT05252845). Existing human papilloma virus and pneumococcal vaccination programmes still do not reach all the populations they should.9Spayne J Hesketh T Estimate of global human papillomavirus vaccination coverage: analysis of country-level indicators.BMJ Open. 2021; 11e052016Crossref PubMed Scopus (20) Google Scholar, 10Ostropolets A Shoener Dunham L Johnson KD Liu J Pneumococcal vaccination coverage among adults newly diagnosed with underlying medical conditions and regional variation in the US.Vaccine. 2022; 40: 4856-4863Crossref PubMed Scopus (4) Google Scholar A vaccine for dengue fever received its first approval for use in Indonesia in August, 2022.11TakedaTakeda's QDENGA® (dengue tetravalent vaccine [live, attenuated]) approved in Indonesia for use regardless of prior dengue exposure.https://www.takeda.com/newsroom/newsreleases/2022/takedas-qdenga-dengue-tetravalent-vaccine-live-attenuated-approved-in-indonesia-for-use-regardless-of-prior-dengue-exposure/Date: Aug 22, 2022Date accessed: October 18, 2022Google Scholar Additionally, new long-acting preventive injectable therapies might be administered by health-care workers in the future—eg, small interfering RNA (siRNA) that prevents translation of PCSK9 for atherosclerotic cardiovascular disease prevention, or the siRNA anti-hypertensive that targets angiotensinogen, if its efficacy is confirmed in ongoing trials (NCT04936035).12US Food and Drug AdministrationFDA approves add-on therapy to lower cholesterol among certain high-risk adults.https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-add-therapy-lower-cholesterol-among-certain-high-risk-adultsDate: Dec 22, 2021Date accessed: October 18, 2022Google Scholar, 13Huang SA Taubel J Fiore G et al.Abstract 14387: dose-related reductions in blood pressure with a RNA interference (RNAi) therapeutic targeting angiotensinogen in hypertensive patients: interim results from a first-in-human phase 1 study of ALN-AGT01.Circulation. 2020; 142A14387-AGoogle Scholar Long-acting injectables for HIV prevention and antipsychotic treatment could similarly have the potential to become part of preventive strategies.14US Food and Drug AdministrationFDA approves first injectable treatment for HIV pre-exposure prevention.https://www.fda.gov/news-events/press-announcements/fda-approves-first-injectable-treatment-hiv-pre-exposure-preventionDate: Dec 20, 2021Date accessed: October 18, 2022Google Scholar, 15National Council for Mental WellbeingGuide to long-acting medications for clinicians and organizations.https://www.thenationalcouncil.org/wp-content/uploads/2021/12/2022.02.02_NC_Updated-Guide-To-LAMs.pdfDate: 2022Date accessed: October 18, 2022Google Scholar Administering each product individually would be challenging due to high delivery costs and prices, especially in low-income and middle-income countries (LMICs). However, bundling delivery could reduce the per unit cost of administration by using shared resources, such as supply chains and health-care workers, for multiple products, and instituting tiered pricing would make these products more affordable for countries with constrained health budgets. Governments and industry have begun building new manufacturing capacity to avoid vaccine inequity. Before the COVID-19 pandemic, the world produced and procured about 5 billion vaccine doses annually.16AirfinityCOVID-19 vaccine production.https://www.ifpma.org/wp-content/uploads/2021/03/Airfinity_global_summit_master_final.pdfDate: 2021Date accessed: October 18, 2022Google Scholar In 2022, the world has the capacity to manufacture more than 25 billion doses of approved COVID-19 vaccines, and most production is concentrated in China, the EU, India, and the USA.16AirfinityCOVID-19 vaccine production.https://www.ifpma.org/wp-content/uploads/2021/03/Airfinity_global_summit_master_final.pdfDate: 2021Date accessed: October 18, 2022Google Scholar, 17UNICEFCOVID-19 Market Dashboard.https://www.unicef.org/supply/covid-19-market-dashboardDate: 2022Date accessed: October 18, 2022Google Scholar Sustainable, scaled, and globally distributed manufacturing would improve the response to future pandemics. As new manufacturing sites are established, coordinated demand forecasts and adoption of routine vaccinations at scale could keep these factories commercially viable so that they are available for the next pathogen outbreak. The COVID-19 pandemic highlighted the role of community-based and primary care sites to deliver vaccines and to build reliable cold chains. There is potential to integrate more preventive health services into a single point of care, reducing the need for vertical systems that focus on single diseases. Indeed, in 2019, two-thirds of global health funding to LMICs focused on HIV, tuberculosis, malaria (which historically have not benefited from long-acting pharmacological preventive technologies), and reproductive, maternal, newborn, and child health.18Institute for Health Metrics and EvaluationFinancing global health. Flows of development assistance for health.https://vizhub.healthdata.org/fgh/Date: 2022Date accessed: October 18, 2022Google Scholar Addressing these patient populations is important and funding should be sustained, but there should also be increased focus on prevention strategies for other adult diseases. These strategies should consider variations in available financing, service delivery, public health infrastructure, disease burden, vaccine acceptance, and other factors across countries. The digitisation of health systems accelerated during the COVID-19 pandemic, and digital tools identified and prioritised individuals for vaccination, recruited them to sites, and in some settings linked vaccination data to health records with a unique identifier. Before the pandemic, about 60% of LMICs did not have electronic immunisation registries.19PATHDigital Square. Electronic immunization registries in low- and middle-income countries.https://static1.squarespace.com/static/59bc3457ccc5c5890fe7cacd/t/60aee1bfd163646306fb924c/1622073794356/Digital+Square+EIR+Landscape_Final.pdfDate: 2021Date accessed: October 18, 2022Google Scholar Digitisation is key to successful vaccine roll-outs, and pressure to build this infrastructure during the pandemic led to considerable progress. This infrastructure will be particularly important given the need for multiple vaccines, repeat boosters, and diagnostic tests for many vaccines or injectables. Not all high-income countries achieved this infrastructure, but those that did created some of the best datasets and real-world evidence on COVID-19 vaccine safety and efficacy.20Dagan N Barda N Kepten E et al.BNT162b2 mRNA COVID-19 vaccine in a nationwide mass vaccination setting.N Engl J Med. 2021; 384: 1412-1423Crossref PubMed Scopus (1511) Google Scholar, 21Lopez Bernal J Andrews N Gower C et al.Effectiveness of the Pfizer-BioNTech and Oxford-AstraZeneca vaccines on COVID-19 related symptoms, hospital admissions, and mortality in older adults in England: test negative case-control study.BMJ. 2021; 373n1088PubMed Google Scholar Many LMICs have or are developing digital health systems that provide a powerful starting point for scaling digitally enabled primary care and public health. Global health funders and governments should require and prioritise digital infrastructure to deliver, track, and measure the impact of adult vaccines, injectables, and other interventions. This approach would enable systems to not only record clinical encounters, but also to collect longitudinal data on demographics, clinical outcomes, and side-effects (including in clinical trials) in a privacy-protected way. This digital infrastructure would facilitate the most effective use of new vaccines and injectable therapies that could transform the prevention agenda and improve pandemic preparedness. The importance of a prevention strategy that capitalises on innovations for infectious and chronic diseases and strengthens health systems is clear, as highlighted in two 2022 reports, A Global Opportunity to Combat Preventable Disease: How to Use COVID-19 Infrastructure to Transform Public Health Worldwide22Alkasir A Berry T Britto D et al.A global opportunity to combat preventable disease: how to use COVID-19 infrastructure to transform public health worldwide. Tony Blair Institute for Global Change, January, 2022https://institute.global/sites/default/files/2022-01/GHSC%2C%20A%20Global%20Opportunity%20to%20Combat%20Preventable%20Disease%2C%20January%202022.pdfDate accessed: October 18, 2022Google Scholar and One Shot to Prevent Disease and Prepare for Future Pandemics.23Agus D Bell J Blair T One shot to prevent disease and prepare for future pandemics. Global Health Security Consortium, October, 2022https://institute.global/sites/default/files/2022-10/GHSC%2C%20Introducing%20One%20Shot%20to%20Prevent%20Disease%20and%20Prepare%20for%20Future%20Pandemics%2C%20October%202022%20FINAL.pdfDate accessed: October 25, 2022Google Scholar Vaccines and preventive injectables that are available or in development could prevent 10 million deaths each year.22Alkasir A Berry T Britto D et al.A global opportunity to combat preventable disease: how to use COVID-19 infrastructure to transform public health worldwide. Tony Blair Institute for Global Change, January, 2022https://institute.global/sites/default/files/2022-01/GHSC%2C%20A%20Global%20Opportunity%20to%20Combat%20Preventable%20Disease%2C%20January%202022.pdfDate accessed: October 18, 2022Google Scholar, 23Agus D Bell J Blair T One shot to prevent disease and prepare for future pandemics. Global Health Security Consortium, October, 2022https://institute.global/sites/default/files/2022-10/GHSC%2C%20Introducing%20One%20Shot%20to%20Prevent%20Disease%20and%20Prepare%20for%20Future%20Pandemics%2C%20October%202022%20FINAL.pdfDate accessed: October 25, 2022Google Scholar A global adult disease prevention programme, supported by geographically distributed manufacturing and digitally enabled cold chain, service delivery, and recording, could have profound implications for health worldwide between disease outbreaks and also create the systems to respond to future pathogen threats. Governments, funders, the private sector, and partner organisations need to overcome siloed efforts to deliver this programme as a positive global legacy of the COVID-19 pandemic. DBA is the paid Founding Director and Chief Executive Officer of the Ellison Institute for Transformative Medicine, a public good for-profit (the Institute comprises both a for-profit entity, whose profits will be reinvested into future public health and disease research, as well as a not-for-profit research foundation), which draws collaborators from across conventional health fields, as well as from a broad range of other disciplines to study disease and potential ways to prevent, detect, and treat the disease, and is a paid faculty member of the University of Southern California. JB is a paid faculty member of Oxford University, a paid Non-Executive Director of Oxford Science Enterprises, an independent investment company that has active investments in life sciences (novel platforms, technologies, and approaches advancing the discovery of new therapeutics and vaccines), health tech (medical devices, tools, digital diagnostics, AI-powered clinical imaging, virtual reality therapy, and solutions to improve health-care delivery), and deep tech (quantum computing and enabling technologies, fusion energy, industrial heat, novel computer hardware, electrified transportation, and solutions to tackle depleting food resources), and is a paid Chair of the Bill & Melinda Gates Foundation's Global Health Scientific Advisory Board. DBA and JB are non-paid Co-Chairs of the Global Health Security Consortium, a partnership to support and guide leaders on the global health security agenda. AN is a paid Special Adviser to Gavi, the Vaccine Alliance. AAS is the paid General Administrator of Institut Pasteur de Dakar, which produces a yellow fever vaccine. We declare no other competing interests. We thank Tamsin Berry, Romina Mariano, Gabriel Seidman, and Emily Stanger Sfeile from the Global Health Security Consortium for their assistance with preparing this Comment. Successful adult vaccine drives must centre disability inclusionThe promise of a vaccine-centred future discussed by David B Agus and colleagues presents an important opportunity for disability inclusion.1 Many novel vaccine candidates target diseases that disproportionately affect people with disabilities, including COVID-19, other respiratory illnesses, and various non-communicable diseases.2 The 10–20-year gap in life expectancy for people with disabilities makes improving inclusion in future public health systems essential.2 Full-Text PDF Successful adult vaccine drives must centre disability inclusion – Authors' replyWe thank Sara Rotenberg and Matthew Downer for their thoughtful Correspondence about the importance of disability inclusion in vaccination strategies. We appreciate their efforts to highlight this topic and agree with its importance. Preventive therapies can have different benefits in different populations, and ensuring their equitable distribution and use in those populations who would benefit most is crucial to their success for the whole population. Full-Text PDF
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