SARS-CoV-2 Neutralization with BNT162b2 Vaccine Dose 3

Falsey, Ann R.; Frenck, Robert W.; Walsh, Edward E.; Kitchin, Nicholas; Absalon, Judith; Gurtman, Alejandra; Lockhart, Stephen; Bailey, Richard; Swanson, Kena A.; Xu, Xia; Koury, Kenneth; Kalina, Warren V.; Cooper, David A.; Zou, Jing; Xie, Xuping; Xia, Hongjie; Türeci, Özlem; Lagkadinou, Eleni; Tompkins, Kristin; Shi, Pei–Yong; Jansen, Kathrin U.; Şahin, Uğur; Dormitzer, Philip R.; Gruber, William C.

doi:10.1056/nejmc2113468

Cited by 376 publications

(347 citation statements)

References 4 publications

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“…At peak immunity, the BNT162b2 vaccine induced a high median live-virus neutralizing antibody titer (1789), a high median pseudovirus neutralizing antibody titer (700), and a high median binding antibody titer against the receptor-binding domain (RBD) (21,564). However, these titers declined sharply by 6 months after vaccination, as previously reported, 1 , 2 and they declined further by 8 months ( Figure 1A through 1C , S1, and S2). By 8 months after BNT162b2 vaccination, the median live-virus neutralizing antibody titer (53), pseudovirus neutralizing antibody titer (160), and RBD-specific binding antibody titer (755) elicited by the vaccine were lower than the peak titers by a factor of 34, 4, and 29, respectively.…”

supporting

confidence: 84%

“…These data show differential kinetics of immune responses induced by the mRNA and Ad26.COV2.S vaccines over an 8-month follow-up period. As shown in previous studies, 1 , 2 the BNT162b2 and mRNA-1273 vaccines were characterized by high peak antibody responses that declined sharply by 6 months; these responses declined further by 8 months. Antibody titers in recipients of the mRNA-1273 vaccine were generally higher than those in recipients of the BNT162b2 vaccine.…”

supporting

confidence: 71%

See 1 more Smart Citation

Differential Kinetics of Immune Responses Elicited by Covid-19 Vaccines

Collier¹,

Yu²,

McMahan³

et al. 2021

N Engl J Med

255

260

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supporting

confidence: 84%

supporting

confidence: 71%

Differential Kinetics of Immune Responses Elicited by Covid-19 Vaccines

Collier¹,

Yu²,

McMahan³

et al. 2021

N Engl J Med

255

260

View full text Add to dashboard Cite

“…23 These data suggest that boosting with the original mRNA-1273 vaccine could maintain continued protection against variants of concern and comports with previous reports. 13,14,21 Data for the neutralization titers against Delta and Beta after Stage 2 and 3 boosts will soon be available.…”

Section: Serum Binding and Neutralizing Antibody Activity Correlates With Protection From Covid-19mentioning

confidence: 99%

Heterologous SARS-CoV-2 Booster Vaccinations – Preliminary Report

Atmar

Lyke

Deming

et al. 2021

Preprint

Self Cite

101

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Background: While Coronavirus disease 2019 (Covid-19) vaccines are highly effective, breakthrough infections are occurring. Booster vaccinations have recently received emergency use authorization (EUA) for certain populations but are restricted to homologous mRNA vaccines. We evaluated homologous and heterologous booster vaccination in persons who had received an EUA Covid-19 vaccine regimen. Methods: In this phase 1/2 open-label clinical trial conducted at ten U.S. sites, adults who received one of three EUA Covid-19 vaccines at least 12 weeks prior to enrollment and had no reported history of SARS-CoV-2 infection received a booster injection with one of three vaccines (Moderna mRNA-1273 100-mcg, Janssen Ad26.COV2.S 5x1010 virus particles, or Pfizer-BioNTech BNT162b2 30-mcg; nine combinations). The primary outcomes were safety, reactogenicity, and humoral immunogenicity on study days 15 and 29. Results: 458 individuals were enrolled: 154 received mRNA-1273, 150 received Ad26.CoV2.S, and 154 received BNT162b2 booster vaccines. Reactogenicity was similar to that reported for the primary series. Injection site pain, malaise, headache, and myalgia occurred in more than half the participants. Booster vaccines increased the neutralizing activity against a D614G pseudovirus (4.2-76-fold) and binding antibody titers (4.6-56-fold) for all combinations; homologous boost increased neutralizing antibody titers 4.2-20-fold whereas heterologous boost increased titers 6.2-76-fold. Day 15 neutralizing and binding antibody titers varied by 28.7-fold and 20.9-fold, respectively, across the nine prime-boost combinations. Conclusion: Homologous and heterologous booster vaccinations were well-tolerated and immunogenic in adults who completed a primary Covid-19 vaccine regimen at least 12 weeks earlier.

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“…One of the most interesting observations of this study is that patients with natural infection, before or soon after the first vaccine injection had significantly higher humoral responses to vaccine than uninfected patients. Because vaccination aims to stimulate immune responses that mirror natural infection, the finding of enhancement of humoral responses to vaccine in MS patients who have acquired infection, often unnoticed, suggests that for certain DMTs such as fingolimod, an additional boost with a third dose of mRNA vaccine is likely to be effective, as already shown for solid-organ transplant recipients (20) and in the general population (21).…”

Section: Previous Sars-cov2 Infections Enhance the Early Humoral Responses To Sars-cov-2 Vaccinementioning

confidence: 98%

“…(B) Antibody response to SARS-CoV-2 vaccination by DMT in MS patients positive for anti-N antibodies. In A and B red dotted lines indicate a cutoff value of 133 U/ml predictive of the presence of neutralizing antibodies according to Resman et al(21). Results are reported as boxplots, showing the median value (in bold) and the quartiles as box limits; whiskers at the top and bottom sides represent the overall maximum value and the overall minimum value, respectively.…”

mentioning

confidence: 99%

Effect of different disease-modifying therapies on humoral response to BNT162b2 vaccine in Sardinian multiple sclerosis patients

Pitzalis

Idda

Lodde

et al. 2021

Preprint

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Objectives: Vaccination against COVID-19 is highly recommended to patients affected by multiple sclerosis (MS); however, the impact of MS disease-modifying therapies (DMTs) on the immune response following vaccination has been only partially investigated. Here, we aimed to elucidate the effect of DMTs on the humoral immune response to mRNA-based anti-SARS-CoV-2 vaccines in MS patients. Methods: We obtained sera from 912 Sardinian MS patients and 63 healthy controls 30 days after the second dose of BNT162b2 vaccine and tested them for SARS-CoV-2 response using anti-Spike (S) protein-based serology. Previous SARS-CoV-2 infection was assessed by anti-Nucleocapsid (N) serology. Patients were either untreated or undergoing treatment with a total of 13 different DMTs. Differences between treatment groups comprised of at least 10 patients were assessed by generalized linear mixed-effects model. Demographic and clinical data and smoking status were analyzed as additional factors potentially influencing humoral immunity from COVID-19 vaccine. Results: MS patients treated with natalizumab, teriflunomide, azathioprine, fingolimod, ocrelizumab, and rituximab showed significantly lower humoral responses compared to untreated patients. We did not observe a statistically significant difference in response between patients treated with the other drugs (dimethyl fumarate, interferon, alemtuzumab and glatiramer acetate) and untreated patients. In addition, older age, male sex and active smoking were significantly associated with lower antibody titers against SARS-CoV-2. MS patients previously infected with SARS-CoV-2 had significantly higher humoral responses to vaccine than uninfected patients. Conclusion: Humoral response to BNT162b2 is significantly influenced by the specific DMTs followed by patients, as well as by other factors such as previous SARS-CoV-2 infection, age, sex, and smoking status. These results are important to inform targeted strategies to prevent clinically relevant COVID-19 in MS patients.

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SARS-CoV-2 Neutralization with BNT162b2 Vaccine Dose 3

Cited by 376 publications

References 4 publications

Differential Kinetics of Immune Responses Elicited by Covid-19 Vaccines

Differential Kinetics of Immune Responses Elicited by Covid-19 Vaccines

Heterologous SARS-CoV-2 Booster Vaccinations – Preliminary Report

Effect of different disease-modifying therapies on humoral response to BNT162b2 vaccine in Sardinian multiple sclerosis patients

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