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Background: Vaccination is one of the most effective public health interventions. We investigate the impact of vaccination activities for Haemophilus influenzae type b, hepatitis B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, rotavirus, rubella, Streptococcus pneumoniae , and yellow fever over the years 2000-2030 across 112 countries., Methods: Twenty-one mathematical models estimated disease burden using standardised demographic and immunisation data. Impact was attributed to the year of vaccination through vaccine-activity-stratified impact ratios., Results: We estimate 97 (95%CrI[80, 120]) million deaths would be averted due to vaccination activities over 2000-2030, with 50 (95%CrI[41, 62]) million deaths averted by activities between 2000 and 2019. For children under-5 born between 2000 and 2030, we estimate 52 (95%CrI[41, 69]) million more deaths would occur over their lifetimes without vaccination against these diseases., Conclusions: This study represents the largest assessment of vaccine impact before COVID-19-related disruptions and provides motivation for sustaining and improving global vaccination coverage in the future., Funding: VIMC is jointly funded by Gavi, the Vaccine Alliance, and the Bill and Melinda Gates Foundation (BMGF) (BMGF grant number: OPP1157270 / INV-009125). Funding from Gavi is channelled via VIMC to the Consortium's modelling groups (VIMC-funded institutions represented in this paper: Imperial College London, London School of Hygiene and Tropical Medicine, Oxford University Clinical Research Unit, Public Health England, Johns Hopkins University, The Pennsylvania State University, Center for Disease Analysis Foundation, Kaiser Permanente Washington, University of Cambridge, University of Notre Dame, Harvard University, Conservatoire National des Arts et Métiers, Emory University, National University of Singapore). Funding from BMGF was used for salaries of the Consortium secretariat (authors represented here: TBH, MJ, XL, SE-L, JT, KW, NMF, KAMG); and channelled via VIMC for travel and subsistence costs of all Consortium members (all authors). We also acknowledge funding from the UK Medical Research Council and Department for International Development, which supported aspects of VIMC's work (MRC grant number: MR/R015600/1).JHH acknowledges funding from National Science Foundation Graduate Research Fellowship; Richard and Peggy Notebaert Premier Fellowship from the University of Notre Dame. BAL acknowledges funding from NIH/NIGMS (grant number R01 GM124280) and NIH/NIAID (grant number R01 AI112970). The Lives Saved Tool (LiST) receives funding support from the Bill and Melinda Gates Foundation.This paper was compiled by all coauthors, including two coauthors from Gavi. Other funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication., Competing Interests: JT, SE, XL, KA, EC, HC, AC, Md, KE, MF, IG, TH, WH, DH, JH, KJ, AK, PK, AK, JL, XL, TM, CM, SM, SN, TP, AP, DR, SR, CS, SS, YT, HT, QT, ST, EV, NW, AW, KW, NF, KG No competing interests declared, MJ MLJ has received research funding from Sanofi Pasteur unrelated to the present work, MJ Reviewing editor, eLife, BL BAL reports grants and personal fees from Takeda Pharmaceuticals, personal fees from World Health Organization, outside the submitted work, TP TAP receives support from Emergent Biosolutions for work unrelated to his contribution to this study, HR HR is an employee of Center for Disease Analysis Foundation which has received grants from Gilead Sciences, AbbVie, Zeshan Foundation and EndHep2030 fund for projects unrelated to this work; HBV epidemiology data was funded by a grant from John Martin Foundation (Grant number 24), CT CLT received a consulting payment from GSK in 2018 (outside the submitted work), (© 2021, Toor et al.)

Background: Sanofi-Pasteur's CYD-TDV is the only licensed dengue vaccine. Two phase three trials showed higher efficacy in seropositive than seronegative recipients. Hospital follow-up revealed increased hospitalisation in 2-5- year-old vaccinees, where serostatus and age effects were unresolved., Methods: We fit a survival model to individual-level data from both trials, including year 1 of hospital follow-up. We determine efficacy by age, serostatus, serotype and severity, and examine efficacy duration and vaccine action mechanism., Results: Our modelling indicates that vaccine-induced immunity is long-lived in seropositive recipients, and therefore that vaccinating seropositives gives higher protection than two natural infections. Long-term increased hospitalisation risk outweighs short-lived immunity in seronegatives. Independently of serostatus, transient immunity increases with age, and is highest against serotype 4. Benefit is higher in seropositives, and risk enhancement is greater in seronegatives, against hospitalised disease than against febrile disease., Conclusions: Our results support vaccinating seropositives only. Rapid diagnostic tests would enable viable 'screen-then-vaccinate' programs. Since CYD-TDV acts as a silent infection, long-term safety of other vaccine candidates must be closely monitored., Funding: Bill & Melinda Gates Foundation, National Institute for Health Research, UK Medical Research Council, Wellcome Trust, Royal Society., Clinical Trial Number: NCT01373281 and NCT01374516., Competing Interests: DL, ID, WH, GN, NF No competing interests declared, LC Laurent Coudeville is employed by Sanofi-Pasteur, (© 2021, Laydon et al.)