Dosing interval strategies for two-dose COVID-19 vaccination in 13 middle-income countries of Europe: Health impact modelling and benefit-risk analysis

Liu, Yang; Pearson, Carl A. B.; Sandmann, Frank; Barnard, Rosanna C.; Kim, Jong-Hoon; Jit, Mark; Abbas, Kaja

doi:10.1016/j.lanepe.2022.100381

Cited by 22 publications

(30 citation statements)

References 33 publications

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“…These adverse effects increase to 56,600 (95% PI: 45,800-71,500) additional hospital admissions and 7,400 (95% PI: 5600-9400) deaths when assuming the lower efficacy against infection associated with a 3-week interval, and values would be even higher if we had assumed that the efficacy against severe disease was reduced by the shorter interval (Table 1). This echoes model-based findings that have been shown for other European countries 19,20 , although here we use a model that more robustly captures the temporal dynamics.…”

Section: Resultssupporting

confidence: 81%

The impacts of SARS-CoV-2 vaccine dose separation and targeting on the COVID-19 epidemic in England

et al. 2023

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In late 2020, the JCVI (the Joint Committee on Vaccination and Immunisation, which provides advice to the Department of Health and Social Care, England) made two important recommendations for the initial roll-out of the COVID-19 vaccine. The first was that vaccines should be targeted to older and vulnerable people, with the aim of maximally preventing disease rather than infection. The second was to increase the interval between first and second doses from 3 to 12 weeks. Here, we re-examine these recommendations through a mathematical model of SARS-CoV-2 infection in England. We show that targeting the most vulnerable had the biggest immediate impact (compared to targeting younger individuals who may be more responsible for transmission). The 12-week delay was also highly beneficial, estimated to have averted between 32-72 thousand hospital admissions and 4-9 thousand deaths over the first ten months of the campaign (December 2020–September 2021) depending on the assumed interaction between dose interval and efficacy.

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Section: Resultssupporting

confidence: 81%

The impacts of SARS-CoV-2 vaccine dose separation and targeting on the COVID-19 epidemic in England

et al. 2023

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“…These adverse effects increase to 56,600 (95% PI: 45,800-71,500) additional hospital admissions and 7,400 (95% PI: 5,600-9,400) deaths when assuming the lower efficacy against infection associated with a 3-week interval; values would be even higher if we had assumed that the efficacy against severe disease was reduced by the shorter interval (Table 1). This echoes other model-based finding for European countries [19,20] although here we use a model that more robustly captures the temporal dynamics.…”

supporting

confidence: 83%

“…In general, we would also expect such results to hold for future pandemics in other geographical or demographic settings whenever first doses generate substantial protection against severe disease in the most vulnerable [9]. However, bespoke models matched to available national data are ideally needed to assess the benefits on a case-by-case basis [20, 22, 23].…”

Section: Discussionmentioning

confidence: 99%

The Impact of SARS-CoV-2 Vaccine Dose Separation and Dose Targeting on Hospital Admissions and Deaths from COVID-19 in England

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Penman

Hill

et al. 2022

Preprint

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In late 2020, the JCVI (the Joint Committee on Vaccination and Immunisation, which provides advice to the Department of Health and Social Care, England) made two important recommendations for the initial roll-out of the COVID-19 vaccine. The first was that vaccines should be targeted to the elderly and vulnerable, with the aim of maximally preventing disease rather than infection - a prioritisation that has become the adopted practice in many countries. The second was to increase the interval between first and second doses for 3 to 12-weeks, which both accounted for the observation that the ChAdOx vaccine appeared to have a higher efficacy with this longer dose interval, and that by delaying second doses the capacity to deliver first doses was increased. Here, using the latest data on vaccine efficacy we re-examine these recommendations through a mathe- matical model, to understand their short and medium-term impacts in England. In particular, we show that targeting the most vulnerable had the biggest immediate impact (compared to targeting younger individuals who may be more responsible for transmission). The 12-week delay was also highly beneficial, estimated to have averted between 32-72 thousand hospital admissions and 4-9 thousand deaths over the first ten months of the campaign (December 2020 - September 2021) - depending on the assumed interaction between dose interval and efficacy.

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“…Most COVID-19 vaccines are given in a two-dose primary schedule, whereas additional booster doses may be required to maintain immunity. The time interval between vaccine administrations can greatly affect the logistics of the vaccination campaign and its efficacy ( 1 – 3 ). The effect of the dosing interval on COVID-19 vaccine efficacy has not been specifically tested in Randomized Clinical Trials (RCT), however, available data suggest that longer intervals between the first and second dose result in higher antibody titers ( 4 ).…”

Section: Introductionmentioning

confidence: 99%

In-silico evaluation of adenoviral COVID-19 vaccination protocols: Assessment of immunological memory up to 6 months after the third dose

et al. 2022

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BackgroundThe immune response to adenoviral COVID-19 vaccines is affected by the interval between doses. The optimal interval is unknown.AimWe aim to explore in-silico the effect of the interval between vaccine administrations on immunogenicity and to analyze the contribution of pre-existing levels of antibodies, plasma cells, and memory B and T lymphocytes.MethodsWe used a stochastic agent-based immune simulation platform to simulate two-dose and three-dose vaccination protocols with an adenoviral vaccine. We identified the model’s parameters fitting anti-Spike antibody levels from individuals immunized with the COVID-19 vaccine AstraZeneca (ChAdOx1-S, Vaxzevria). We used several statistical methods, such as principal component analysis and binary classification, to analyze the correlation between pre-existing levels of antibodies, plasma cells, and memory B and T cells to the magnitude of the antibody response following a booster dose.Results and conclusionsWe find that the magnitude of the antibody response to a booster depends on the number of pre-existing memory B cells, which, in turn, is highly correlated to the number of T helper cells and plasma cells, and the antibody titers. Pre-existing memory T cytotoxic cells and antibodies directly influence antigen availability hence limiting the magnitude of the immune response. The optimal immunogenicity of the third dose is achieved over a large time window, spanning from 6 to 16 months after the second dose. Interestingly, after any vaccine dose, individuals can be classified into two groups, sustainers and decayers, that differ in the kinetics of decline of their antibody titers due to differences in long-lived plasma cells. This suggests that the decayers may benefit from a tailored boosting schedule with a shorter interval to avoid the temporary loss of serological immunity.

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Dosing interval strategies for two-dose COVID-19 vaccination in 13 middle-income countries of Europe: Health impact modelling and benefit-risk analysis

Cited by 22 publications

References 33 publications

The impacts of SARS-CoV-2 vaccine dose separation and targeting on the COVID-19 epidemic in England

The impacts of SARS-CoV-2 vaccine dose separation and targeting on the COVID-19 epidemic in England

The Impact of SARS-CoV-2 Vaccine Dose Separation and Dose Targeting on Hospital Admissions and Deaths from COVID-19 in England

In-silico evaluation of adenoviral COVID-19 vaccination protocols: Assessment of immunological memory up to 6 months after the third dose

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