Effectiveness of mRNA BNT162b2 COVID-19 vaccine up to 6 months in a large integrated health system in the USA: a retrospective cohort study

Tartof, Sara Y.; Slezak, Jeff; Fischer, Heidi; Hong, Vennis; Ackerson, Bradley; Ranasinghe, Omesh N; Frankland, Timothy B.; Ogun, Oluwaseye Ayoola; Zamparo, Joann M.; Gray, Sharon; Valluri, Srinivas Rao; Pan, Kaije; Angulo, Frederick J.; Jódar, Luis; McLaughlin, John M.

doi:10.1016/s0140-6736(21)02183-8

Cited by 1,048 publications

(1,108 citation statements)

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“…At seven months past dose two for BNT162b2 we predict IgG levels to drop to 0.16 percent of the peak response; suggesting that 0.16% of the peak response correlates to 16% efficacy. In another BNT162b2 study, against infection was found to decline to 47% five months post dose two, with efficacy against the delta variant found to be 53% four months after full vaccination [37]. We find that following two standard doses of BNT162b2 the IgG counts have dropped to 2.1 and 7.2 percent of peak, five and four months following the second dose, respectively.…”

Section: Discussionmentioning

confidence: 54%

Long-term predictions of humoral immunity after two doses of BNT162b2 and mRNA-1273 vaccines based on dosage, age and sex

Korosec

Farhang‐Sardroodi

Dick

et al. 2021

Preprint

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Background. The lipid nanoparticle (LNP)-formulated mRNA vaccines are a widely adopted two-dose vaccination public health strategy to manage the COVID-19 pandemic. Clinical trial data has described the immunogeneicity of the vaccine, albeit within a limited study time frame. Our aims were to use a within-host mathematical model for LNP-formulated mRNA vaccines, informed by available clinical trial data, to project a longer term understanding of humoral immunity as a function of vaccine type, dosage amount, age, and sex. Methods. We developed a mathematical model describing the immunization process of LNP-formulated mRNA vaccines, and fit our model to twenty-two clinical humoral and cytokine BNT162b2 or mRNA-1273 human two-dose vaccination data sets. We incorporated multi-dose effects in our model to specify whether the dosage is standard or low-dose. We further specify the age groups 18-55, 56-70, and 70+ in our fits for two-standard doses of mRNA-1273, and sex in our fits for two-standard doses of BNT162b2. We used non-linear mixed effect models to fit to all similar data types (e.g. standard two-dose BNT162b2 or mRNA-1273, or two low-dose mRNA-1273). Therefore, in our fits all estimated parameters are statistically correlated, which allowed us to determine the underlying 'population-dynamics' structure common to a data type. We therefore made accurate long-term predictions informed by all clinical data used in this study. Findings. We estimate that two standard doses of either mRNA-1273 or BNT162b2, with dosage times separated by the company-mandated intervals, results in individuals loosing more than 99% humoral immunity relative to peak immunity by eight months following the second dose. We predict that within an eight month period following dose two (corresponding to the CDC time-frame for administration of a third dose), there exists a period of time longer than one month where an individual has less then 99% humoral immunity relative to peak immunity, regardless of which vaccine was administered. We further find that age has a strong influence in maintaining humoral immunity; by eight months following dose two we predict that individuals aged 18-55 have a four-fold humoral advantage compared to aged 56-70 and 70+ individuals. We find that sex has little effect on the vaccine uptake and long-term IgG counts. Finally, we find that humoral immunity generated from two low doses of mRNA-1273 decays substantially slower relative to peak immunity gained than compared to two standard doses of either mRNA-1273 or BNT162b2. Interpretation. For the two dose mRNA vaccines, our predictions highlight the importance of the recommended third booster dose in order to maintain elevated levels of antibodies. We further show that age plays a critical role in determining the antibody levels. Hence, a third booster dose may confer an immuno-protective advantage in older individuals.

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Section: Discussionmentioning

confidence: 54%

Long-term predictions of humoral immunity after two doses of BNT162b2 and mRNA-1273 vaccines based on dosage, age and sex

Korosec

Farhang‐Sardroodi

Dick

et al. 2021

Preprint

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“…Together, these data identify durable cellular immunity for at least 6 months after mRNA vaccination with persistence of high-quality memory B cells and strong CD4+ T cell memory in most individuals. These data may also provide context for understanding potential discrepancies in vaccine efficacy at preventing infection versus severe disease, hospitalization, and death (10,11). Declining antibody titers over time likely reduce the potential that vaccination will completely prevent infection or provide near-sterilizing immunity.…”

Section: Discussionmentioning

confidence: 99%

“…This decline from peak antibody levels may be associated with an increase in infections over time compared to the initial months post-vaccination (8, 9). Yet, vaccine-induced immunity remains highly effective at preventing severe disease, hospitalization, and death even at later timepoints when antibody levels may decline (10)(11)(12).Previous research has largely focused on responses early in the course of vaccination, with transcriptional analysis identifying potential links between myeloid cell responses and neutralizing antibodies (13).…”

mentioning

confidence: 99%

mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern

Goel¹,

Painter²,

Apostolidis³

et al. 2021

Science

658

125

739

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The coronavirus disease 2019 (COVID-19) pandemic has resulted in significant morbidity and mortality worldwide. Community-level immunity, acquired through infection or vaccination, is necessary to control the pandemic as the virus continues to circulate (1). mRNA vaccines encoding a stabilized version of the full-length SARS-CoV-2 Spike protein have been widely administered and clinical trial data demonstrated up to 95% efficacy in preventing symptomatic COVID-19 (2, 3). These mRNA vaccines induce potent humoral immune responses, with neutralizing antibody titers proposed as the major correlate of protection (4-6). Current evidence suggests that circulating antibodies persist for at least 6 months post-vaccination (7), though there is some decay from peak levels achieved after the second dose. This decline from peak antibody levels may be associated with an increase in infections over time compared to the initial months post-vaccination (8, 9). Yet, vaccine-induced immunity remains highly effective at preventing severe disease, hospitalization, and death even at later timepoints when antibody levels may decline (10)(11)(12).Previous research has largely focused on responses early in the course of vaccination, with transcriptional analysis identifying potential links between myeloid cell responses and neutralizing antibodies (13).

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“…Since the end of December 2020, the World Health Organization (WHO) had identified several COVID-19 vaccines that have been shown to be efficacious in lowering the risk of contracting COVID-19 during controlled clinical trials in the WHO Emergency Use Listing [2]. As crucial tools in the pandemic response, COVID-19 vaccines also demonstrated accumulating evidence of protection against severe disease, hospitalization, and death [3][4][5]. While vaccination provides individuals protection against the virus [6], researchers also advocate a high-level community vaccination coverage to minimize the impact of COVID-19 on society [7].…”

Section: Introductionmentioning

confidence: 99%

Cognitive Factors Influencing COVID-19 Vaccination Intentions: An Application of the Protection Motivation Theory Using a Probability Community Sample

Tong

et al. 2021

Vaccines

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COVID-19 vaccines, as one of the effective ways of dealing with the COVID-19 pandemic, can lower COVID-19 risk and protect against severe disease and death; however, substantial individual differences in vaccination intentions have hindered the realization of a high vaccination rate among the public. To look for efficient strategies to promote vaccination, this study tested whether the protection motivation theory (PMT), a cognitive model based upon threat and coping appraisals, would account for the differences in vaccination intentions under three scenarios (i.e., vaccines in general and with high- or low- efficacy of lowering the risk of developing COVID-19). A phone survey was conducted in early 2021 and obtained a probability community sample (n = 472; 49.2% men) in Macao, China. We found that 54.0% of respondents indicated their relatively strong intention to receive COVID-19 vaccination for high-efficacy vaccines, compared to 29.5% for low-efficacy vaccines and 31.0% for vaccines in general. After controlling for demographics, self-efficacy (i.e., the perceived capability of receiving COVID-19 vaccines) and maladaptive response reward (i.e., the perceived benefits of not receiving COVID-19 vaccines) were consistently associated with COVID-19 vaccination intentions under all three scenarios. The perceived severity of COVID-19 infection and response cost of COVID-19 vaccination were significantly associated with vaccination intention for high-efficacy vaccines, while the response efficacy of lowering the COVID-19 impact with COVID-19 vaccination was positively associated with vaccination intention for general and low-efficacy vaccines. Given that the relative strength of PMT constructs depends on perceived vaccine efficacy, we recommend taking PMT constructs and vaccine efficacy into account for encouraging vaccination.

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Effectiveness of mRNA BNT162b2 COVID-19 vaccine up to 6 months in a large integrated health system in the USA: a retrospective cohort study

Cited by 1,048 publications

References 34 publications

Long-term predictions of humoral immunity after two doses of BNT162b2 and mRNA-1273 vaccines based on dosage, age and sex

Long-term predictions of humoral immunity after two doses of BNT162b2 and mRNA-1273 vaccines based on dosage, age and sex

mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern

Cognitive Factors Influencing COVID-19 Vaccination Intentions: An Application of the Protection Motivation Theory Using a Probability Community Sample

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