Biontech schutz nach erster impfung

List des authors.Fernando P. Polack, M.D., Stephen J. Thomas, M.D., nikolaus Kitchin, M.D., Judith Absalon, M.D., Alejandra Gurtman, M.D., Stephen Lockhart, D.M., john L. Perez, M.D., gonzo Pérez Marc, M.D., Edson D. Moreira, M.D., Cristiano Zerbini, M.D., Ruth Bailey, B.Sc., Kena A. Swanson, Ph.D., Satrajit Roychoudhury, Ph.D., Kenneth Koury, Ph.D., Ping Li, Ph.D., Warren V. Kalina, Ph.D., david Cooper, Ph.D., robert W. Frenck, Jr., M.D., Laura L. Hammitt, M.D., Özlem Türeci, M.D., Haylene Nell, M.D., Axel Schaefer, M.D., Serhat Ünal, M.D., Dina B. Tresnan, D.V.M., Ph.D., Susan Mather, M.D., Philip R. Dormitzer, M.D., Ph.D., Uğur Şahin, M.D., kathrin U. Jansen, Ph.D., und William C. Gruber, M.D.

Du schaust: Biontech schutz nach erster impfung

et al.,

A complete list of investigators bei the C4591001 Clinical Trial group is provided bei the Supplementary Appendix, available at futbolpublic.com.


Drs. Polack and Thomas contributed equally to this article.


Metrics


Abstract

Background

Severe acute respiratory tract syndrome covid 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) schutz afflicted tens des millions des people in a global pandemic. Safe and effective vaccines are essential urgently.

Methods

*

Download a PDF von the research study Summary.

In in ongoing multinational, placebo-controlled, observer-blinded, pivotal efficacy trial, us randomly assigned persons 16 years of age or older in a 1:1 ratio to receive two doses, 21 job apart, of either placebo or ns BNT162b2 vaccine candidate (30 μg per dose). BNT162b2 zu sein a lipid nanoparticle–formulated, nucleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. Ns primary end points to be efficacy von the vaccine against laboratory-confirmed Covid-19 und safety.

Results

A total von 43,548 participants underwent randomization, of whom 43,448 got injections: 21,720 v BNT162b2 and 21,728 through placebo. There were 8 situations of covid19 with onset hinweisen least 7 job after the second dose amongst participants assigned zu receive BNT162b2 and 162 cases amongst those assigned kommen sie placebo; BNT162b2 was 95% effective bei preventing covid-19 (95% credible interval, 90.3 zu 97.6). Similar vaccine efficacy (generally 90 zu 100%) was observed across subgroups defined von age, sex, race, ethnicity, baseline body-mass index, und the presence of coexisting conditions. Among 10 cases von severe covid19 with onset after the first dose, 9 occurred in placebo recipients und 1 bei a BNT162b2 recipient. The safety profile of BNT162b2 was characterized by short-term, mild-to-moderate ache at die injection site, fatigue, and headache. Ns incidence des serious adverse events was low und was similar in the vaccine and placebo groups.

Conclusions

A two-dose regimen des BNT162b2 conferred 95% protection against Covid-19 an persons 16 years von age or older. Safety over a median von 2 months was similar zu that von other famous vaccines. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.)

Introduction


*
QUICK TAKESafety and Efficacy von the BNT162b2 covid-19 Vaccine 03:00

Coronavirus disease 2019 (Covid-19) has influenced tens des millions des people globally1 since it was declared a pandemic von the world Health organization on march 11, 2020.2 enlarge adults, people with certain coexisting conditions, und front-line workers are at highest risk for Covid-19 und its complications. Recent dünn show increasing rates von severe acute respiratory tract syndrome covid 2 (SARS-CoV-2) infection und Covid-19 in other populations, including younger adults.3 Safe und effective prophylactic vaccines space urgently needed zu contain the pandemic, which has actually had devastating medical, economic, und social consequences.

We formerly reported schritt 1 safety and immunogenicity results from clinical trials of the vaccine candidate BNT162b2,4 a lipid nanoparticle–formulated,5 nucleoside-modified RNA (modRNA)6 encoding the SARS-CoV-2 full-length spike, modified über two proline mutations kommen sie lock it bei the prefusion conformation.7 findings from studies conducted in the vereinigt States and Germany among gesund men and women confirmed that two 30-μg doses des BNT162b2 elicited high SARS-CoV-2 neutralizing antibody titers und robust antigen-specific CD8+ und Th1-type CD4+ T-cell responses.8 ns 50% neutralizing geometric median titers elicited von 30 μg des BNT162b2 bei older and younger adult exceeded die geometric typical titer measured an a human being convalescent serum panel, in spite of a reduced neutralizing response bei older adult than in younger adults. In addition, ns reactogenicity profile des BNT162b2 represented mainly short-term local (i.e., injection site) und systemic responses. This findings supported progression of the BNT162b2 vaccine candidate into bühne 3.

Here, us report safety and efficacy result from the phase 2/3 part des a global phase 1/2/3 trial evaluating die safety, immunogenicity, and efficacy des 30 μg of BNT162b2 an preventing Covid-19 in persons 16 years von age or older. This charme set and these trial outcomes are the basis for in application for emergency use authorization.9 Collection of phase 2/3 säule on vaccine immunogenicity and the durability of the immune response zu immunization ist ongoing, and those säule are notfall reported here.

Mehr sehen: Darf Ich Meine Cousine Heiraten, Sämmtliche Werke: In Zwölf Bänden


Trial Objectives, Participants and Oversight

We assessed ns safety und efficacy des two 30-μg doses of BNT162b2, administered intramuscularly 21 job apart, as contrasted with placebo. Adult 16 years des age or older that were gesund or had actually stable chronic clinical conditions, consisting of but not limited kommen sie human immunodeficiency viruist (HIV), hepatitis b virus, or hepatitis ns virus infection, to be eligible for participation in the trial. An essential exclusion criteria included a clinical history von Covid-19, treatment with immunosuppressive therapy, or diagnosis with in immunocompromising condition.

Pfizer was responsible zum the design and conduct von the trial, charme collection, data analysis, säule interpretation, und the writing von the manuscript. BioNTech was the sponsor of ns trial, manufactured ns BNT162b2 clinical attempt material, and contributed to die interpretation von the data und the writing von the manuscript. All the trial dünn were available zu all die authors, who vouch weil das its accuracy and completeness und for adherence von the trial to the protocol, which zu sein available with ns full text von this article at futbolpublic.com. In independent data and safety monitoring board reviewed efficacy and unblinded security data.

Trial Procedures

With ns use of in interactive Web-based system, participants in the trial were randomly assigned an a 1:1 ratio kommen sie receive 30 μg des BNT162b2 (0.3 ml volume per dose) or saline placebo. Participants got two injections, 21 job apart, des either BNT162b2 or placebo, delivered in the deltoid muscle. Website staff that were responsible weil das safety evaluation and were unaware of kopieren, gruppe assignments it was observed participants for 30 minute after vaccination zum any acute reactions.

Safety

The primary ende points des this trial were solicited, particular local or systemic disadvantage events and use des antipyretic or pain medication within 7 days after ns receipt des each dose des vaccine or placebo, as triggered by und recorded in bei electronic diary an a subset of participants (the reactogenicity subset), und unsolicited adverse occasions (those reported by the participants without prompts from die electronic diary) through 1 month after the second dose und unsolicited major adverse events through 6 month after the second dose. Adverse event dünn through roughly 14 weeks after ns second dose space included bei this report. In this report, safety säule are reported for all entrants who provided informed consent und received hinweisen least one dose of vaccine or placebo. Von protocol, safety and security results zum participants infected v HIV (196 patients) möchte be analyzed separately und are not included here.

During the bühne 2/3 portion des the study, a preventing rule weil das the theoretical concern des vaccine-enhanced disease was zu be triggered if ns one-sided probability von observing die same or a an ext unfavorable adverse major case break-up (a separation with a better proportion of severe cases an vaccine recipients) was 5% or less, given ns same true incidence weil das vaccine and placebo recipients. Alarm criteria were zu be triggered if this probability was less than 11%.

Efficacy

The zuerst primary end point was the efficacy von BNT162b2 against confirmed covid19 with onset punkt least 7 days after ns second dose in participants who had been without serologic or virologic evidence of SARS-CoV-2 infection up kommen sie 7 job after the second dose; the second primary ende point was efficacy in participants with und participants there is no evidence des prior infection. Confirmed covid19 was characterized according to the Food and Drug administration (FDA) criteria as the presence von at the very least one of the following symptoms: fever, neu or boosted cough, neu or enhanced shortness of breath, chills, new or increased muscle pain, neu loss of basic or smell, sick throat, diarrhea, or vomiting, merged with a respiratory specimen acquired during the symptomatic duration or within 4 days before or after it that was positive for SARS-CoV-2 von nucleic mountain amplification–based testing, either at ns central activities or punkt a local testing facility (using a protocol-defined acceptable test).

Major secondary end points included the efficacy of BNT162b2 versus severe Covid-19. Severe covid19 is defined by the FDA together confirmed covid-19 with one of the following extr features: clinical signs punkt rest that room indicative of severe systemic illness; respiratory tract failure; evidence von shock; far-ranging acute renal, hepatic, or neurologic dysfunction; admission to bei intensive treatment unit; or death. Einzelheiten are provided bei the protocol.

An explanation des the assorted denominator values zum use an assessing the results of the trial is provided in Table S1 in the Supplementary Appendix, available at futbolpublic.com. An brief, the safety population includes persons 16 years of age or older; a total of 43,448 participants comprised the population of enrolled people injected with ns vaccine or placebo. The main safety subset as defined über the FDA, with a median des 2 months des follow-up as of October 9, 2020, consisted of 37,706 persons, and the reactogenicity subset consisted von 8183 persons. Ns modified intention-to-treat (mITT) efficacy population includes all age groups 12 years of age or older (43,355 persons; 100 participants who were 12 to fünfzehn years of age contributed zu person-time years but included no cases). The number von persons who might be evaluated zum efficacy 7 work after ns second dose und who had actually no evidence des prior infection was 36,523, and the number des persons who might be evaluate 7 days after die second dose through or there is no evidence des prior infection was 40,137.

Statistical Analysis

The safety and security analyses had all participants who received punkt least one dose des BNT162b2 or placebo. Ns findings room descriptive in nature and not based on formal statistical theory testing. Safety and security analyses space presented as counts, percentages, und associated Clopper–Pearson 95% trust intervals for local reactions, systemic events, and any adverse occasions after vaccination, according to terms in the clinical Dictionary zum Regulatory tasks (MedDRA), ausführung 23.1, for each vaccine group.

Mehr sehen: Ni No Kuni Remastered Im Test: 'Ich Bin Ich Verliebt In Ihn Test

Analysis des the first primary efficacy end point contained participants who received the vaccine or placebo together randomly assigned, had no evidence von infection in ~ 7 work after ns second dose, und had no major protocol deviations (the population that can be evaluated). Vaccine efficacy was estimated von 100×(1−IRR), wherein IRR ist the calculate ratio of confirmed instances of covid19 illness per 1000 person-years des follow-up in the active vaccine group to the corresponding disease rate in the placebo group. The 95.0% credible interval zum vaccine efficacy und the probability von vaccine efficacy greater than 30% to be calculated with the use des a Bayesian beta-binomial model. Die final evaluation uses a success boundary des 98.6% zum probability von vaccine efficacy higher than 30% kommen sie compensate weil das the interim analysis und to control ns overall kind 1 error rate at 2.5%. Moreover, primary and secondary efficacy ende points room evaluated sequentially zu control ns familywise kind 1 verfehlt rate hinweisen 2.5%. Descriptive analyses (estimates of vaccine efficacy and 95% trust intervals) space provided for key subgroups.