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Estimates of the global health impact of immunisation are important for quantifying historical benefits as well as planning future investments and strategy. The Vaccine Impact Modelling Consortium (VIMC) was established in 2016 to provide reliable estimates of the health impact of immunisation. In this article we examine the consortium in its first five-year phase. We detail how vaccine impact was defined and the methods used to estimate it as well as the technical infrastructure required to underpin robust reproducibility of the outputs. We highlight some of the applications of estimates to date, how these were communicated and what their effect were. Finally, we explore some of the lessons learnt and remaining challenges for estimating the impact of vaccines and forming effective modelling consortia then discuss how this may be addressed in the second phase of VIMC. Modelled estimates are not a replacement for surveillance; however, they can examine theoretical counterfactuals and highlight data gaps to complement other activities. VIMC has implemented strategies to produce robust, standardised estimates of immunisation impact. But through the first phase of the consortium, critical lessons have been learnt both on the technical infrastructure and the effective engagement with modellers and stakeholders. To be successful, a productive dialogue with estimate consumers, producers and stakeholders needs to be underpinned by a rigorous and transparent analytical framework as well as an approach for building expertise in the short and long term., Competing Interests: Competing interests: KAMG, XL, HC, ED, RF, WH, DH, MJ, TM, TAP, AP, EV, KW, NMF, CLT, received funding from Gavi, BMGF and/or the Wellcome Trust via VIMC during the course of the study. The authors declare no other competing interests., (Copyright: © 2024 Gaythorpe KAM et al.)

Background: WHO, as requested by its member states, launched the Expanded Programme on Immunization (EPI) in 1974 to make life-saving vaccines available to all globally. To mark the 50-year anniversary of EPI, we sought to quantify the public health impact of vaccination globally since the programme's inception., Methods: In this modelling study, we used a suite of mathematical and statistical models to estimate the global and regional public health impact of 50 years of vaccination against 14 pathogens in EPI. For the modelled pathogens, we considered coverage of all routine and supplementary vaccines delivered since 1974 and estimated the mortality and morbidity averted for each age cohort relative to a hypothetical scenario of no historical vaccination. We then used these modelled outcomes to estimate the contribution of vaccination to globally declining infant and child mortality rates over this period., Findings: Since 1974, vaccination has averted 154 million deaths, including 146 million among children younger than 5 years of whom 101 million were infants younger than 1 year. For every death averted, 66 years of full health were gained on average, translating to 10·2 billion years of full health gained. We estimate that vaccination has accounted for 40% of the observed decline in global infant mortality, 52% in the African region. In 2024, a child younger than 10 years is 40% more likely to survive to their next birthday relative to a hypothetical scenario of no historical vaccination. Increased survival probability is observed even well into late adulthood., Interpretation: Since 1974 substantial gains in childhood survival have occurred in every global region. We estimate that EPI has provided the single greatest contribution to improved infant survival over the past 50 years. In the context of strengthening primary health care, our results show that equitable universal access to immunisation remains crucial to sustain health gains and continue to save future lives from preventable infectious mortality., Funding: WHO., Competing Interests: Declaration of interests CLT and KAMG assert that their employer, Imperial College, receives funding for the Vaccine Impact Modelling Consortium from the Bill & Melinda Gates Foundation; Gavi, the Vaccine Alliance; and the Wellcome Trust. CLT has received consulting fees from GSK for attending an advisory board meeting on CMV vaccines in May, 2022 and is pro bono Chair of the Scientific Advisory Panel of the Meningitis Research Foundation. HF asserts that her employer, London School of Hygiene & Tropical Medicine, receives funding for the Vaccine Impact Modelling Consortium from the Gates Foundation. JFM asserts that his employer, University of Washington, receives grant funding from Gavi and from the Gates Foundation. KB and KMT assert that their organisation Kid Risk holds a cooperative agreement with the US Centers for Disease Control and Prevention and holds grants from the Gates Foundation. MJF asserts that his employer, Penn State University, is a subrecipient of funds from Imperial College London for a grant from Gavi and that he holds grants from the Gates Foundation and the US National Science Foundation. MJ asserts that his employer, London School of Hygiene & Tropical Medicine, receives funding from the UK National Institute of Health Research, RCUK; the Gates Foundation; Gavi; the Wellcome Trust; WHO; the European Commission; the US Centers for Disease Control and Prevention; the Hong Kong Special Administrative Region Government; and the Task Force for Global Health. RAH and SPS assert that their employer, University of Cape Town, receives grant funding from the African Field Epidemiology Network and the US Centers for Disease Control and Prevention. RGW asserts that he receives funding from the Wellcome Trust (grant numbers 218261/Z/19/Z), National Institutes of Health (1R01AI147321-01, G-202303-69963, and R-202309-71190), European and Developing Countries Clinical Trials Partnership (RIA208D-2505B), UK Medical Research Council (CCF17-7779 via SET Bloomsbury), UK Economic and Social Research Council (ES/P008011/1), Bill & Melinda Gates Foundation (INV-004737 and INV-035506), and WHO (2020/985800-0). AL, KLO-B, NB-Z, PL, RCWH, and SYS work for WHO. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: There have been declines in global immunisation coverage due to the COVID-19 pandemic. Recovery has begun but is geographically variable. This disruption has led to under-immunised cohorts and interrupted progress in reducing vaccine-preventable disease burden. There have, so far, been few studies of the effects of coverage disruption on vaccine effects. We aimed to quantify the effects of vaccine-coverage disruption on routine and campaign immunisation services, identify cohorts and regions that could particularly benefit from catch-up activities, and establish if losses in effect could be recovered., Methods: For this modelling study, we used modelling groups from the Vaccine Impact Modelling Consortium from 112 low-income and middle-income countries to estimate vaccine effect for 14 pathogens. One set of modelling estimates used vaccine-coverage data from 1937 to 2021 for a subset of vaccine-preventable, outbreak-prone or priority diseases (ie, measles, rubella, hepatitis B, human papillomavirus [HPV], meningitis A, and yellow fever) to examine mitigation measures, hereafter referred to as recovery runs. The second set of estimates were conducted with vaccine-coverage data from 1937 to 2020, used to calculate effect ratios (ie, the burden averted per dose) for all 14 included vaccines and diseases, hereafter referred to as full runs. Both runs were modelled from Jan 1, 2000, to Dec 31, 2100. Countries were included if they were in the Gavi, the Vaccine Alliance portfolio; had notable burden; or had notable strategic vaccination activities. These countries represented the majority of global vaccine-preventable disease burden. Vaccine coverage was informed by historical estimates from WHO-UNICEF Estimates of National Immunization Coverage and the immunisation repository of WHO for data up to and including 2021. From 2022 onwards, we estimated coverage on the basis of guidance about campaign frequency, non-linear assumptions about the recovery of routine immunisation to pre-disruption magnitude, and 2030 endpoints informed by the WHO Immunization Agenda 2030 aims and expert consultation. We examined three main scenarios: no disruption, baseline recovery, and baseline recovery and catch-up., Findings: We estimated that disruption to measles, rubella, HPV, hepatitis B, meningitis A, and yellow fever vaccination could lead to 49 119 additional deaths (95% credible interval [CrI] 17 248-134 941) during calendar years 2020-30, largely due to measles. For years of vaccination 2020-30 for all 14 pathogens, disruption could lead to a 2·66% (95% CrI 2·52-2·81) reduction in long-term effect from 37 378 194 deaths averted (34 450 249-40 241 202) to 36 410 559 deaths averted (33 515 397-39 241 799). We estimated that catch-up activities could avert 78·9% (40·4-151·4) of excess deaths between calendar years 2023 and 2030 (ie, 18 900 [7037-60 223] of 25 356 [9859-75 073])., Interpretation: Our results highlight the importance of the timing of catch-up activities, considering estimated burden to improve vaccine coverage in affected cohorts. We estimated that mitigation measures for measles and yellow fever were particularly effective at reducing excess burden in the short term. Additionally, the high long-term effect of HPV vaccine as an important cervical-cancer prevention tool warrants continued immunisation efforts after disruption., Funding: The Vaccine Impact Modelling Consortium, funded by Gavi, the Vaccine Alliance and the Bill & Melinda Gates Foundation., Translations: For the Arabic, Chinese, French, Portguese and Spanish translations of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests A-MH, XL, SE-L, JR, KA, MA, MJdV, MJF, KF, HF, TH, MJ, AK, SMM, SN, TP, TAP, AP, QTM, EV, AKW, HB, CC, HEC, AD, SH, JH, KJ, CK, J-HK, JK, BAL, VEP, YT, KW, NMF, CLT, and KAMG received funding from Gavi, the Vaccine Alliance and the Bill & Melinda Gates Foundation via the Vaccine Impact Modelling Consortium (VIMC) during the study. A-MH, JR, SE-L, XL, SN, MJdV, TH, WH, KW, NMF, CLT, and KAMG receive funding from the Medical Research Council Centre for Global Infectious Disease Analysis (reference MR/R015600/1), which is jointly funded by the UK Medical Research Council and the UK Foreign, Commonwealth, and Development Office under a concordant agreement, and is also part of the European and Developing Countries Clinical Trials Partnership programme supported by the EU. A-MH, JR, SE-L, XL, SN, MJdV, TH, WH, KW, NMF, CLT, and KAMG receive funding from Community Jameel. A-MH is supported by the German Federal Ministry of Education and Research (grant 01LN2210A) and declares stock options in BIONTECH. CLT received payment for advice from GlaxoSmithKline. KA is supported by the Japan Agency for Medical Research and Development (JP223fa627004). KAMG received a speaker fee from Sanofi Pasteur. SN receives consulting fees from WHO. VEP is a member of the WHO Immunization and Implementation Research Advisory Committee. BAL receives personal fees from Epidemiologic Research and Methods and Hillevax. SMM receives consultant fees from Emergent Biosolutions. NMF receives grant funding from Janssen Pharmaceuticals, UK Research and Innovation, and the UK National Institute for Health and Care Research; declares consulting fees from the World Bank, WHO, and Gavi; receives travel expenses for WHO meetings; was on an advisory board for Takeda; and is a senior editor for eLife. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)