Sustained T Cell Immunity, Protection and Boosting Using Extended Dosing Intervals of BNT162b2 mRNA Vaccine

Payne, Rebecca; Longet, Stéphanie; Austin, James; Skelly, Donal; Dejnirattisai, Wanwisa; Adele, Sandra; Meardon, Naomi; Faustini, Sian; Al-Taei, Saly; Moore, Shona C.; Tipton, Tom; Hering, Luisa M.; Angyal, Adrienn; Brown, Rachael; Gillson, Natalie; Dobson, Susan L; Amini, Ali; Supasa, Piyada; Cross, Andrew; Sandhar, Gurjinder; Kilby, J A; Tyerman, Jessica K.; Nicols, Alexander R.; Altmann, Thomas; Hornsby, Hailey; Whitham, Ruth H.; Phillips, Eloise; Malone, Tom; Hargreaves, Alexander; Shields, Adrian; Saei, Ayoub; Foulkes, Sarah; Stafford, Lizzie; Johnson, Síle A.; Wootton, Daniel G.; Conlon, Christopher P.; Jeffery, Katie; Matthews, Philippa C.; Frater, John; Deeks, Alexandra; Dold, Christina; Pollard, Andrew J.; Brown, Aaron; Rowland‐Jones, Sarah; Mongkolsapaya, Juthathip; Barnes, Eleanor; Hopkins, Susan; Hall, Victoria; Duncan, Christopher; Richter, Alex; Carroll, Maria V.; Screaton, Gavin; Silva, T D; Turtle, Lance; Klenerman, Paul; Dunachie, Susanna

doi:10.2139/ssrn.3891065

Cited by 33 publications

(31 citation statements)

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“…While few clinical trials included variation in dose spacing, the trial of AZD1222 (AstraZeneca) varied the interval between doses and found that efficacy increased from 55% with less than 6 weeks between doses to 81% with more than 12 weeks 50 . In real-world settings, this interval often varied due to explicit policies of delaying second doses in favor of universal partial vaccination 125,126 , allowing for evaluation of its impact on both nAb levels and VE 7,16,127 . Currently, while most vaccine manufacturers and international advisory committees (including WHO 128 ) recommend that initial and subsequent vaccine doses be with the same product - as this was the regimen tested in clinical trials - many countries have adopted more flexible policies allowing for “mixing and matching” of doses 129–131 , often in response to supply constraints.…”

Section: Discussionmentioning

confidence: 99%

A systematic review of COVID-19 vaccine efficacy and effectiveness against SARS-CoV-2 infection and disease

Higdon

Wahl

Jones

et al. 2021

Preprint

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Billions of doses of COVID-19 vaccines have been administered around the world, dramatically reducing SARS-CoV-2 incidence in some settings. Many studies suggest vaccines provide a high degree of protection against infection and disease, but precise estimates vary and studies differ in design, outcomes measured, dosing regime, location, and circulating virus strains. Here we conduct a systematic review of COVID-19 vaccines as of August 2021. We included efficacy data from Phase 3 clinical trials for 13 vaccines within the WHO Emergency Use Listing evaluation process and real-world effectiveness for 5 vaccines with observational studies meeting inclusion criteria. Vaccine metrics collected include effects against asymptomatic infection, any infection, symptomatic COVID-19, and severe outcomes including hospitalization and death, for both partial and complete vaccination, and against SARS-CoV-2 variants of concern. In addition, we review the epidemiological principles behind the design and interpretation of vaccine effects, and explain important sources of heterogeneity between studies.

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Section: Discussionmentioning

confidence: 99%

A systematic review of COVID-19 vaccine efficacy and effectiveness against SARS-CoV-2 infection and disease

Higdon

Wahl

Jones

et al. 2021

Preprint

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“…Recent studies have suggested that BNT162b2 extended dosing intervals yield much higher antibody neutralising and IgG responses than the original 3-week interval, including a UK study on 175 older adults comparing 12-week and 3-week intervals 2-3 weeks post-second dose 7 , the PITCH study on 503 UK healthcare workers comparing 6–14-week and 3-4 week intervals 4 weeks post-second dose 8 , and another UK study on 569 adults comparing >6-week and 3-week intervals 14-34 days post-second dose 9 . These differences are plausibly related to these studies only measuring antibody levels at specific time points after second vaccination, which may not be optimal for comparison ( Figure 1 ), given the 3-week dosing interval antibody levels increasing from 3-6 weeks post-second dose.…”

Section: Discussionmentioning

confidence: 99%

“…Although the ChOxAd1 trial found higher vaccine efficacy with dosing intervals ≥6 weeks 6 , BNT162b2 trials did not compare different dosing intervals. Subsequent UK studies showed extended BNT162b2 dosing intervals generated a higher antibody response than the 3-week interval [7][8][9] . However, these studies were based on relatively small sample sizes (N<600) or specific population groups such as healthcare workers, potentially reducing generalisability, and antibody levels were only measured at specific times after second doses.…”

Section: Current Word Count: 3946mentioning

confidence: 99%

SARS-CoV-2 anti-spike IgG antibody responses after second dose of ChAdOx1 or BNT162b2 and correlates of protection in the UK general population

Wei

Pouwels

Stoesser

et al. 2021

Preprint

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We investigated anti-spike IgG antibody responses following second doses of ChAdOx1 or BNT162b2 SARS-CoV-2 vaccines in the UK general population. In 186,527 individuals, we found significant boosting of anti-spike IgG by second doses of both vaccines in all ages and using different dosing intervals, including the 3-week interval for BNT162b2. After second vaccination, BNT162b2 generated higher peak levels than ChAdOX1. Antibody levels declined faster at older ages than younger ages with BNT162b2, but were similar across ages with ChAdOX1. With both vaccines, prior infection significantly increased antibody peak level and half-life. Protection was estimated to last for 0.5-1 year after ChAdOx1 and >1 year after BNT162b2, but could be reduced against emerging variants. Reducing the dosing interval to 8 weeks for both vaccines or further to 3 weeks for BNT162b2 may help increase short-term protection against the Delta variant. A third booster dose may be needed, prioritised to more vulnerable people.

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“…Interestingly, delaying the time (6-14 weeks) between first and second doses of the Pfizer-BioNTech (BNT162b2) mRNA and Oxford-AstraZeneca (AZD1222/ChAdOx1) vaccines resulted in higher neutralizing antibody levels compared to the three-week interval tested during vaccine licensing clinical trials (85)(86)(87)(88). CD4 + and CD8 + T-lymphocyte responses were however slightly dampened with a longer time interval (87,88). It has been postulated that these observations may be attributed to the longer time interval allowing more S-specific T-lymphocytes to differentiate into memory T-lymphocytes that respond more effectively upon re-exposure to the S protein (88).…”

Section: Vaccine-induced Neutralizing Antibody Responses To Sars-cov-2mentioning

confidence: 99%

SARS-CoV-2 Variants, Vaccines, and Host Immunity

et al. 2022

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new beta coronavirus that emerged at the end of 2019 in the Hubei province of China. SARS-CoV-2 causes coronavirus disease 2019 (COVID-19) and was declared a pandemic by the World Health Organization (WHO) on 11 March 2020. Herd or community immunity has been proposed as a strategy to protect the vulnerable, and can be established through immunity from past infection or vaccination. Whether SARS-CoV-2 infection results in the development of a reservoir of resilient memory cells is under investigation. Vaccines have been developed at an unprecedented rate and 7 408 870 760 vaccine doses have been administered worldwide. Recently emerged SARS-CoV-2 variants are more transmissible with a reduced sensitivity to immune mechanisms. This is due to the presence of amino acid substitutions in the spike protein, which confer a selective advantage. The emergence of variants therefore poses a risk for vaccine effectiveness and long-term immunity, and it is crucial therefore to determine the effectiveness of vaccines against currently circulating variants. Here we review both SARS-CoV-2-induced host immune activation and vaccine-induced immune responses, highlighting the responses of immune memory cells that are key indicators of host immunity. We further discuss how variants emerge and the currently circulating variants of concern (VOC), with particular focus on implications for vaccine effectiveness. Finally, we describe new antibody treatments and future vaccine approaches that will be important as we navigate through the COVID-19 pandemic.

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Sustained T Cell Immunity, Protection and Boosting Using Extended Dosing Intervals of BNT162b2 mRNA Vaccine

Cited by 33 publications

References 0 publications

A systematic review of COVID-19 vaccine efficacy and effectiveness against SARS-CoV-2 infection and disease

A systematic review of COVID-19 vaccine efficacy and effectiveness against SARS-CoV-2 infection and disease

SARS-CoV-2 anti-spike IgG antibody responses after second dose of ChAdOx1 or BNT162b2 and correlates of protection in the UK general population

SARS-CoV-2 Variants, Vaccines, and Host Immunity

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