Prospective Monitoring of BNT162b2 Second Vaccination Booster Effects in Health Care Workers (HCW)

Prospective Monitoring of BNT162b2 Second Vaccination Booster for Prevention of the COVID-19 Infection in Health Care Workers (HCW)

The SARS-CoV-2 virus causes severe respiratory illness and is an ongoing global pandemic. On December 12, 2020 the FDA approved Pfizer's BioNTech vaccine BNT162b2 which is a messenger RNA type of vaccine for use. This vaccine has shown in numerous studies the ability to induce a strong immune response and provide both humeral and cellular protection against wild type, alpha and delta variants of SARS-CoV2 virus.

In Israel the national vaccine operation began in mid-December 2020 which included 2 initial doses three weeks apart. In August 2021 a first booster (3rd dose) was provided to enhance protection and due to reports of reduced immune response and clinical protection. Several studies have demonstrated that over time there is a decay in the antibody levels, and with them reduced protection.

Recently a new variant of concern has been identified (Omicron) and is causing a surge of infections worldwide. There is lack of knowledge regarding the effectiveness of the current schedule of vaccine against this new variant and whether a second booster (4th dose) will provide higher levels of clinical protection against this variant, currently the ministry of health is considering recommendations for a fourth dose for HCW.

The purpose of this study is to examine whether a fourth dose of vaccination will provide better protection against infection and clinical disease.

Study Overview

• Status: Active, not recruiting
• Conditions: Coronavirus Infections
• Intervention / Treatment: Biological: Pfizer BNT162b2 Vaccine

• Study Type: Observational
• Enrollment (Actual): 635

Contacts and Locations

Study Locations

• Israel
  • Beer- Sheva, Israel, 84101
    • Soroka UMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The study population will be screened at each participating medical center. The study population will be enrolled according to the following inclusion and exclusion criteria.

Description

Inclusion Criteria:

1. Able to provide written informed consent.
2. Healthcare worker in one of the Clalit Health Services Medical centers and is at least 18 years of age.
3. Completed three doses of BNT162b2 according to MOH guidelines.
4. Third dose was given at least 4 months prior to enrollment.

Exclusion Criteria:

1. History of COVID-19 infection.
2. History of being treated or is currently being treated for any type of Malignancies or other co-morbid conditions that may result in protocol non-compliance.
3. Currently or in the past three months was treated with any type of Immune suppression medication (including chemotherapy, immunomodulatory drugs, biological agents that affect the immune system, any immunosuppressive drug such as corticosteroids).
4. Received in the past 4 months monoclonal antibodies of any type.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Three doses of vaccination; Subjects received three pfizer BNT162b2 vaccination at least four month before recruitment
Four doses of vaccination; Subjects received three pfizer BNT162b2 vaccination at least four month before recruitment and decided to receive another dose at time of recruitment or followup	Biological: Pfizer BNT162b2 Vaccine; The Pfizer-BioNTech COVID-19 vaccine (INN: tozinameran), sold under the brand name Comirnaty, is an mRNA-based COVID-19 vaccine developed by the German biotechnology company BioNTech. For its development, BioNTech collaborated with American company Pfizer to carry out clinical trials, logistics, and manufacturing. It is authorized for use in people aged five years and older in some jurisdictions, twelve years and older in some jurisdictions, and for people sixteen years and older in other jurisdictions, to provide protection against COVID-19, caused by infection with the SARS-CoV-2 virus. The vaccine is given by intramuscular injection. It is composed of nucleoside-modified mRNA (modRNA) encoding a mutated form of the full-length spike protein of SARS-CoV-2, which is encapsulated in lipid nanoparticles. Initial advice indicated that vaccination required two doses given 21 days apart, but the interval was later extended to up to 42 days in the US, and up to four months in Canada

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of positive PCR test for SARS-COV2	Percent Positive PCR test	30 days
Proportion of positive PCR test for SARS-COV2	Percent Positive PCR test	60 days
Proportion of positive PCR test for SARS-COV2	Percent Positive PCR test	90 days
Proportion of positive PCR test for SARS-COV2	Percent Positive PCR test	120 days
Proportion of positive PCR test for SARS-COV2	Percent Positive PCR test	150 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Levels of binding and neutralizing activity and avidity of the antibodies	binding antibody units per mL	30 days
Proportion of symptomatic COVID 19 infection	Percent Positive PCR test	30 days
Proportion of symptomatic COVID 19 infection	Percent Positive PCR test	90 days
Proportion of symptomatic COVID 19 infection	Percent Positive PCR test	182 days
Proportion of COVID 19 infection requiring hospitalization	Percent Positive PCR test	30days
Proportion of COVID 19 infection requiring hospitalization	Percent Positive PCR test	90 days
Proportion of COVID 19 infection requiring hospitalization	Percent Positive PCR test	182 days
Levels of binding and neutralizing activity and avidity of the antibodies	50 Percent neutralization titer	60 days
Levels of binding and neutralizing activity and avidity of the antibodies	50 Percent neutralization titer	90 days
Levels of binding and neutralizing activity and avidity of the antibodies	50 Percent neutralization titer	120 days
Levels of binding and neutralizing activity and avidity of the antibodies	50 Percent neutralization titer	150 days
Levels of binding and neutralizing activity and avidity of the antibodies	50 Percent neutralization titer	180 days
Composite endpoint of serious adverse events	Percent Positive Anaphylaxis, Myocarditis	14 days following the booster vaccination

Collaborators and Investigators

• Sponsor: Soroka University Medical Center
• Collaborators: Ben-Gurion University of the Negev

Study record dates

Study Major Dates

• Study Start (Actual): January 6, 2022
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: August 21, 2022
• First Submitted That Met QC Criteria: August 24, 2022
• First Posted (Actual): August 25, 2022

Study Record Updates

• Last Update Posted (Estimate): May 5, 2023
• Last Update Submitted That Met QC Criteria: May 3, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Coronavirus Infections; Infections
• Other Study ID Numbers: SCRC22001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Unidentified participant data will be made available when the study is complete upon requests directed to the corresponding author. Proposals will be reviewed and approved by the sponsor, investigator, and collaborators on the basis of scientific merit. After approval of a proposal, data can be shared through a secure online platform after signing a data access agreement. All data will be made available for a minimum of 5 years from the end of the study.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes