https://www.medrxiv.org/content/10.1101/2022.02.15.22270948v1 Skip to main content medRxiv * Home * About * Submit * ALERTS / RSS Search for this keyword [ ] [Search] Advanced Search 4th Dose COVID mRNA Vaccines' Immunogenicity & Efficacy Against Omicron VOC View ORCID ProfileGili Regev-Yochay, Tal Gonen, Mayan Gilboa, Michal Mandelboim, Victoria Indenbaum, Sharon Amit, Lilac Meltzer, Keren Asraf, Carmit Cohen, Ronen Fluss, Asaf Biber, Ital Nemet, Limor Kliker, Gili Joseph, Ram Doolman, Ella Mendelson, Laurence S. Freedman, Dror Harats, Yitshak Kreiss, Yaniv Lustig doi: https://doi.org/10.1101/2022.02.15.22270948 Gili Regev-Yochay 1The Infection Prevention & Control Unit, Sheba Medical Center, Tel Hashomer, Israel 2Sackler Faculty of Medicine, Tel-Aviv University, Israel * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site * ORCID record for Gili Regev-Yochay * For correspondence: gili.regev@sheba.health.gov.il Tal Gonen 1The Infection Prevention & Control Unit, Sheba Medical Center, Tel Hashomer, Israel 2Sackler Faculty of Medicine, Tel-Aviv University, Israel * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Mayan Gilboa 1The Infection Prevention & Control Unit, Sheba Medical Center, Tel Hashomer, Israel 2Sackler Faculty of Medicine, Tel-Aviv University, Israel * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Michal Mandelboim 2Sackler Faculty of Medicine, Tel-Aviv University, Israel 3Central Virology Laboratory, Public Health Services, Ministry of Health, Sheba Medical Center, Tel-Hashomer, Israel * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Victoria Indenbaum 3Central Virology Laboratory, Public Health Services, Ministry of Health, Sheba Medical Center, Tel-Hashomer, Israel * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Sharon Amit 4Clinical Microbiology, Sheba Medical Center * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Lilac Meltzer 1The Infection Prevention & Control Unit, Sheba Medical Center, Tel Hashomer, Israel 2Sackler Faculty of Medicine, Tel-Aviv University, Israel * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Keren Asraf 5Automated Mega-Laboratory, Laboratory division, Sheba Medical Center * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Carmit Cohen 1The Infection Prevention & Control Unit, Sheba Medical Center, Tel Hashomer, Israel * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Ronen Fluss 6Biostatistics and Biomathematics Unit, Gertner Institute of Epidemiology and Health Policy Research, Sheba Medical Center, Tel Hashomer, Israel * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Asaf Biber 1The Infection Prevention & Control Unit, Sheba Medical Center, Tel Hashomer, Israel 2Sackler Faculty of Medicine, Tel-Aviv University, Israel * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Ital Nemet 3Central Virology Laboratory, Public Health Services, Ministry of Health, Sheba Medical Center, Tel-Hashomer, Israel * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Limor Kliker 2Sackler Faculty of Medicine, Tel-Aviv University, Israel 3Central Virology Laboratory, Public Health Services, Ministry of Health, Sheba Medical Center, Tel-Hashomer, Israel * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Gili Joseph 1The Infection Prevention & Control Unit, Sheba Medical Center, Tel Hashomer, Israel * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Ram Doolman 5Automated Mega-Laboratory, Laboratory division, Sheba Medical Center * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Ella Mendelson 2Sackler Faculty of Medicine, Tel-Aviv University, Israel 3Central Virology Laboratory, Public Health Services, Ministry of Health, Sheba Medical Center, Tel-Hashomer, Israel * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Laurence S. Freedman 6Biostatistics and Biomathematics Unit, Gertner Institute of Epidemiology and Health Policy Research, Sheba Medical Center, Tel Hashomer, Israel * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Dror Harats 7The Sheba Medical Center Management, Sheba Medical Center, Tel Hashomer, Israel * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Yitshak Kreiss 7The Sheba Medical Center Management, Sheba Medical Center, Tel Hashomer, Israel * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Yaniv Lustig 2Sackler Faculty of Medicine, Tel-Aviv University, Israel 3Central Virology Laboratory, Public Health Services, Ministry of Health, Sheba Medical Center, Tel-Hashomer, Israel * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site * Abstract * Full Text * Info/History * Metrics * Data/Code * Preview PDF Loading Abstract BACKGROUND Following the emergence of the Omicron variant of concern, we investigated immunogenicity, efficacy and safety of BNT162b2 or mRNA1273 fourth dose in an open-label, clinical intervention trial. METHODS Primary end-points were safety and immunogenicity and secondary end-points were vaccine efficacy in preventing SARS-CoV-2 infections and COVID-19 symptomatic disease. The two intervention arms were compared to a matched control group. Eligible participants were healthcare-workers (HCW) vaccinated with three BNT162b2 doses, and whose IgG antibody levels were <=700 BAU (40-percentile). IgG and neutralizing titers, direct neutralization of live VOCs, and T-cell activation were assessed. All participants were actively screened for SARS-CoV-2 infections on a weekly basis. RESULTS Of 1050 eligible HCW, 154 and 120 were enrolled to receive BNT162b2 and mRNA1273, respectively, and compared to 426 age-matched controls. Recipients of both vaccine types had a ~9-10-fold increase in IgG and neutralizing titers within 2 weeks of vaccination and an 8-fold increase in live Omicron VOC neutralization, restoring titers to those measured after the third vaccine dose. Breakthrough infections were common, mostly very mild, yet, with high viral loads. Vaccine efficacy against infection was 30% (95%CI:-9% to 55%) and 11% (95%CI:-43% to +43%) for BNT162b2 and mRNA1273, respectively. Local and systemic adverse reactions were reported in 80% and 40%, respectively. CONCLUSIONS The fourth COVID-19 mRNA dose restores antibody titers to peak post-third dose titers. Low efficacy in preventing mild or asymptomatic Omicron infections and the infectious potential of breakthrough cases raise the urgency of next generation vaccine development. Trial registration number clicaltrials.gov: NCT05231005, NCT05230953 Competing Interest Statement GRY recieved an unrelated research grant from Pfizer (on pneumococcal infections), and from Nanosense on volatile organic compounds Clinical Trial clinicaltrial NCT05231005, NCT05230953 Funding Statement This study did not receive any external funding. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Sheba Medical Center IRB gave ethical approval for the work, as well as the national MOH IRB committee. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Data Availability All data produced in the present study will be available upon reasonable request to the authors Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. View the discussion thread. Back to top PreviousNext Posted February 15, 2022. 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[Send Message] Share 4th Dose COVID mRNA Vaccines' Immunogenicity & Efficacy Against Omicron VOC Gili Regev-Yochay, Tal Gonen, Mayan Gilboa, Michal Mandelboim, Victoria Indenbaum, Sharon Amit, Lilac Meltzer, Keren Asraf, Carmit Cohen, Ronen Fluss, Asaf Biber, Ital Nemet, Limor Kliker, Gili Joseph , Ram Doolman, Ella Mendelson, Laurence S. Freedman, Dror Harats, Yitshak Kreiss, Yaniv Lustig medRxiv 2022.02.15.22270948; doi: https://doi.org/10.1101/ 2022.02.15.22270948 Share This Article: [https://www.medrxiv.org/content/10.1101/2022.02.15] Copy Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo Citation Tools 4th Dose COVID mRNA Vaccines' Immunogenicity & Efficacy Against Omicron VOC Gili Regev-Yochay, Tal Gonen, Mayan Gilboa, Michal Mandelboim, Victoria Indenbaum, Sharon Amit, Lilac Meltzer, Keren Asraf, Carmit Cohen, Ronen Fluss, Asaf Biber, Ital Nemet, Limor Kliker, Gili Joseph , Ram Doolman, Ella Mendelson, Laurence S. 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