COVID-19 vaccine breakthrough infections

Gupta, Ravindra; Topol, Eric J.

doi:10.1126/science.abl8487

Cited by 90 publications

(80 citation statements)

References 7 publications

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“…Thus, future studies should continue monitoring the trend using more recent data or panel data if available. Additional studies might also focus on the booster uptake since vaccine efficacy wanes over time and the booster has become increasingly necessary [26] . Second, in addition to the three factors included in the present study, scholars might consider other factors (e.g., personal experience with the virus and government mandate) that might also shape one’s decision to take the vaccine and change the mindsets of anti-vaxxers.…”

Section: Discussionmentioning

confidence: 99%

Understanding the influence of political orientation, social network, and economic recovery on COVID-19 vaccine uptake among Americans

Feng

Shao

2022

Vaccine

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Section: Discussionmentioning

confidence: 99%

Understanding the influence of political orientation, social network, and economic recovery on COVID-19 vaccine uptake among Americans

Feng

Shao

2022

Vaccine

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“…Unfortunately, on one hand, there is strong resistance to accepting the vaccine, and on the other hand, poor countries do not have supplies for their populations. This worsens the situation as it gives time for new mutations of the virus to develop with a relatively high potential for breakthrough cases (Gupta and Topol, 2021). Consequently, it requires continuously new research and constantly new treatment strategies.…”

Section: Introductionmentioning

confidence: 99%

Towards an optimal monoclonal antibody with higher binding affinity to the receptor-binding domain of SARS-CoV-2 spike proteins from different variants

Neamţu

Mocci

Laaksonen

et al. 2022

Preprint

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A highly efficient and robust multiple scales in silico protocol, consisting of atomistic constant charge Molecular Dynamics (MD), constant-charge coarse-grain (CG) MD and constant-pH CG Monte Carlo (MC), has been used to study the binding affinities, the free energy of complexation of selected antigen-binding fragments of the monoclonal antibody (mAbs) CR3022 (originally derived from SARS-CoV-1 patients almost two decades ago) and 11 SARS-CoV-2 variants including the wild type. CR3022 binds strongly to the receptor-binding domain (RBD) of SARS-CoV-2 spike protein, but chooses a different site rather than the receptor-binding motif (RBM) of RBD, allowing its combined use with other mAbs against new emerging virus variants. Totally 235,000 mAbs structures were generated using the RosettaAntibodyDesign software, resulting in top 10 scored CR3022-RBD complexes with critical mutations and compared to the native one, all having the potential to block virus-host cell interaction. Of these 10 finalists, two candidates were further identified in the CG simulations to be clearly best against all virus variants, and surprisingly, all 10 candidates and the native CR3022 did exhibit a higher affinity for the Omicron variant with its highest number of mutations (15) of them all considered in this study. The multiscale protocol gives us a powerful rational tool to design efficient mAbs. The electrostatic interactions play a crucial role and appear to be controlling the affinity and complex building. Clearly, mAbs carrying a lower net charge show a higher affinity. Structural determinants could be identified in atomistic simulations and their roles are discussed in detail to further hint at a strategy towards designing the best RBD binder. Although the SARS-CoV-2 was specifically targeted in this work, our approach is generally suitable for many diseases and viral and bacterial pathogens, leukemia, cancer, multiple sclerosis, rheumatoid, arthritis, lupus, and more.

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“…Breakthrough SARS-CoV-2 infections in individuals who have received two doses of a COVID-19 vaccine are now routinely reported [1,2] . These are partially attributed to anti-spike antibody (anti-S) waning within several months of receiving the second dose and to the emergence of new variants [3][4][5][6] . Consequently, the UK government initiated a booster vaccination campaign, initially targeting people over the age 50, adults deemed clinically vulnerable to severe COVID-19 outcomes, care home residents, frontline health workers, and household contacts of immunocompromised individuals [7] .…”

Section: Introductionmentioning

confidence: 99%

Anti-spike antibody trajectories in individuals previously immunised with BNT162b2 or ChAdOx1 following a BNT162b2 booster dose

Yavlinsky

Beale

Nguyen

et al. 2022

Preprint

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The two most commonly-used SARS-CoV-2 vaccines in the UK, BNT162b2 (Pfizer-BioNTech) and ChAdOx1 nCoV-19 (Oxford-AstraZeneca), employ different immunogenic mechanisms. Compared to BNT162b2, two-dose immunisation with ChAdOx1 induces substantially lower peak anti-spike antibody (anti-S) levels and is associated with a higher risk of breakthrough infections. To provide preliminary indication of how a third booster BNT162b2 dose impacts anti-S levels, we performed a cross-sectional analysis using capillary blood samples from vaccinated adults (aged ≥18 years) participating in Virus Watch, a prospective community cohort study in England and Wales. Blood samples were analysed using Roche Elecsys Anti-SARS-CoV-2 S immunoassay. We analysed anti-S levels by week since the third dose for vaccines administered on or after September 1, 2021 and stratified the results by second dose vaccine type (ChAdOx1 or BNT162b2), age, sex and clinical vulnerability. Anti-S levels peaked at two weeks post-booster for BNT162b2 (22,185 U/mL; 95%CI: 21,406-22,990) and ChAdOx1 second dose recipients (19,203 U/mL; 95%CI: 18,094-20,377). These were higher than the corresponding peak antibody levels post-second dose for BNT162b2 (12,386 U/mL; 95%CI: 9,801-15,653, week 2) and ChAdOx1 (1,192 U/mL; 95%CI: 818-1735, week 3). No differences emerged by second dose vaccine type, age, sex or clinical vulnerability. Anti-S levels declined post-booster for BNT162b2 (half-life=44 days) and ChAdOx1 second dose recipients (half-life=40 days). These rates of decline were steeper than those post-second dose for BNT162b2 (half-life=54 days) and ChAdOx1 (half-life=80 days). Our findings suggest that peak anti-S levels are higher post-booster than post-second dose, but that levels are projected to be similar after six months for BNT162b2 recipients. Higher peak anti-S levels post-booster may partially explain the increased effectiveness of booster vaccination compared to two-dose vaccination against symptomatic infection with the Omicron variant. Faster waning trajectories post third-dose may have implications for the timing of future booster campaigns or four-dose vaccination regimens for the clinically vulnerable.

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COVID-19 vaccine breakthrough infections

Abstract: Vaccine efficacy wanes over time but can be fully restored with a booster dose

Cited by 90 publications

References 7 publications

Understanding the influence of political orientation, social network, and economic recovery on COVID-19 vaccine uptake among Americans

Understanding the influence of political orientation, social network, and economic recovery on COVID-19 vaccine uptake among Americans

Towards an optimal monoclonal antibody with higher binding affinity to the receptor-binding domain of SARS-CoV-2 spike proteins from different variants

Anti-spike antibody trajectories in individuals previously immunised with BNT162b2 or ChAdOx1 following a BNT162b2 booster dose

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