Waning Immunity after the BNT162b2 Vaccine in Israel
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Abstract
BACKGROUND: In December 2020, Israel began a mass vaccination campaign against coronavirus disease 2019 (Covid-19) by administering the BNT162b2 vaccine, which led to a sharp curtailing of the outbreak. After a period with almost no cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, a resurgent Covid-19 outbreak began in mid-June 2021. Possible reasons for the resurgence were reduced vaccine effectiveness against the delta (B.1.617.2) variant and waning immunity. The extent of waning immunity of the vaccine against the delta variant in Israel is unclear. METHODS: We used data on confirmed infection and severe disease collected from an Israeli national database for the period of July 11 to 31, 2021, for all Israeli residents who had been fully vaccinated before June 2021. We used a Poisson regression model to compare rates of confirmed SARS-CoV-2 infection and severe Covid-19 among persons vaccinated during different time periods, with stratification according to age group and with adjustment for possible confounding factors. RESULTS: Among persons 60 years of age or older, the rate of infection in the July 11-31 period was higher among persons who became fully vaccinated in January 2021 (when they were first eligible) than among those fully vaccinated 2 months later, in March (rate ratio, 1.6; 95% confidence interval [CI], 1.3 to 2.0). Among persons 40 to 59 years of age, the rate ratio for infection among those fully vaccinated in February (when they were first eligible), as compared with 2 months later, in April, was 1.7 (95% CI, 1.4 to 2.1). Among persons 16 to 39 years of age, the rate ratio for infection among those fully vaccinated in March (when they were first eligible), as compared with 2 months later, in May, was 1.6 (95% CI, 1.3 to 2.0). The rate ratio for severe disease among persons fully vaccinated in the month when they were first eligible, as compared with those fully vaccinated in March, was 1.8 (95% CI, 1.1 to 2.9) among persons 60 years of age or older and 2.2 (95% CI, 0.6 to 7.7) among those 40 to 59 years of age; owing to small numbers, the rate ratio could not be calculated among persons 16 to 39 years of age. CONCLUSIONS: These findings indicate that immunity against the delta variant of SARS-CoV-2 waned in all age groups a few months after receipt of the second dose of vaccine.
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Third-dose effectiveness may be declining faster than that of the second dose.
“However, it seems that effectiveness could be declining faster than that of the second dose6,19.”
From Waning effectiveness of the third dose of the BNT162b2 mRNA COVID-19 vaccine (2022) · cites this paper as [19]
The Results (Descriptive Analysis; page unavailable) and Discussion report waning immunity after the second dose. The Discussion mentions a third dose only as a booster approved in response to those findings; it does not assess third-dose effectiveness or compare its rate of decline with that after the second dose. (LLM, conf=0.86)
Experimental — accuracy not yet measuredAdditional vaccine effectiveness studies revealed waning of vaccine-induced protection over time.
“However, as vaccination campaigns progressed, additional vaccine effectiveness (VE) studies revealed waning of the vaccine-induced protection over time [8-13]”
Owing to reduced efficacy of LNP-mRNA vaccines over time and the emergence of highly transmissible SARS-CoV-2 variants such as delta and omicron, the effects of booster vaccination are being examined.
“Owing to the reduced efficacy of LNP-mRNA vaccines over time and the emergence of highly transmissible SARS-CoV-2 variants such as delta (B.1.617.2) and omicron (B.1.1.529),109,110 the effects of booster vaccination are being examined.”
From COVID-19 mRNA vaccines: Platforms and current developments (2022) · cites this paper as [109]
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Cites
Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant
Lopez Bernal, J., Andrews, N., Gower, C., Gallagher, E., Simmons, R., Thelwall, S., Stowe, J., Tessier, E., Groves, N., Dabrera, G., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2108891 · Cited by 2,889 · see citing works
BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting
Dagan, N., Barda, N., Kepten, E., Miron, O., Perchik, S., Katz, M. A., Hernán, M. A., Lipsitch, M., Reis, B., & Balicer, R. D. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2101765 · Cited by 2,527 · see citing works
Haas, E. J., Angulo, F. J., McLaughlin, J. M., Anis, E., Singer, S. R., Khan, F., Brooks, N., Smaja, M., Mircus, G., Pan, K., et al. (2021) · The Lancet · doi:10.1016/s0140-6736(21)00947-8 · Cited by 1,564 · see citing works
Self-citationCorrelation of SARS-CoV-2-breakthrough infections to time-from-vaccine
Mizrahi, B., Lotan, R., Kalkstein, N., Peretz, A., Perez, G., Ben-Tov, A., Chodick, G., Gazit, S., & Patalon, T. (2021) · Nature Communications · doi:10.1038/s41467-021-26672-3 · Cited by 261 · see citing works
Flagged first, then by citations
Research works printed but not linked: 11
- [2]2. Mor O, Zuckerman NS, Hazan I, et al. BNT162b2 vaccination efficacy is marginally affected by the SARS-CoV-2 B.1.351 variant in fully vaccinated individuals. July 19, 2021. (https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3878825). preprint.
- [3]3. Abu-Raddad LJ, Chemaitelly H, Butt AA, et al. Effectiveness of the BNT162b2 Covid-19 vaccine against the B.1.1.7 and B.1.351 variants. N Engl J Med 2021;385:187-189.
- [5]5. Sheikh A, McMenamin J, Taylor B, Robertson C. SARS-CoV-2 delta VOC in Scotland: demographics, risk of hospital admission, and vaccine effectiveness. Lancet 2021;397:2461-2462.
- [7]7. Tang P, Hasan MR, Chemaitelly H, et al. BNT162b2 and mRNA-1273 COVID-19 vaccine effectiveness against the Delta (B.1.617.2) variant in Qatar. August 11, 2021. (https://www.medrxiv.org/content/10.1101/2021.08.11.21261885v1). preprint. · DOI
- [8]8. Puranik A, Lenehan PJ, Silvert E, et al. Comparison of two highly-effective mRNA vaccines for COVID-19 during periods of Alpha and Delta variant prevalence. August 21, 2021. (https://www.medrxiv.org/content/10.1101/2021.08.06.21261707v3). preprint. · DOI
- [9]9. Thomas SJ, Moreira ED Jr, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine through 6 months. N Engl J Med. DOI: 10.1056/NEJMoa2110345. · DOI · Paper page
- [11]11. Puranik A, Lenehan PJ, O’Horo JC, et al. Durability analysis of the highly effective BNT162b2 vaccine against COVID-19. September 7, 2021. (https://www.medrxiv.org/content/10.1101/2021.09.04.21263115v1). preprint. · DOI
- [12]12. Khoury DS, Cromer D, Reynaldi A, et al. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nat Med 2021;27:1205-1211.
- [15]15. Goldberg Y, Mandel M, Woodbridge Y, et al. Protection of previous SARS-CoV-2 infection is similar to that of BNT162b2 vaccine protection: a three-month nationwide experience from Israel. April 24, 2021. (https://www.medrxiv.org/content/10.1101/2021.04.20.21255670v1). preprint. · DOI
- [18]18. Muhsen K, Na’aminh W, Lapidot Y, et al. A nationwide analysis of population group differences in the COVID-19 epidemic in Israel, February 2020–February 2021. Lancet Reg Health Eur 2021;7:100130-100130.
- [20]20. Wall EC, Wu M, Harvey R, et al. Neutralising antibody activity against SARS-CoV-2 VOCs B.1.617.2 and B.1.351 by BNT162b2 vaccination. Lancet 2021;397:2331-2333.
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Effectiveness of COVID-19 vaccines against the Omicron (B.1.1.529) variant of concern
Andrews, N., Stowe, J., Kirsebom, F., Toffa, S., Rickeard, T., Gallagher, E., Gower, C., Kall, M., Groves, N., O’Connell, A.-M., et al. (2021) · doi:10.1101/2021.12.14.21267615 · Cited by 2,420 · see citing works
Feikin, D. R., Higdon, M. M., Abu-Raddad, L. J., Andrews, N., Araos, R., Goldberg, Y., Groome, M. J., Huppert, A., O'Brien, K. L., Smith, P. G., et al. (2022) · The Lancet · doi:10.1016/s0140-6736(22)00152-0 · Cited by 1,237 · see citing works
Self-citationCele, S., Jackson, L., Khoury, D. S., Khan, K., Moyo-Gwete, T., Tegally, H., San, J. E., Cromer, D., Scheepers, C., Amoako, D., et al. (2021) · doi:10.1101/2021.12.08.21267417 · Cited by 1,333 · see citing works
Protection against SARS-CoV-2 after Covid-19 Vaccination and Previous Infection
Hall, V., Foulkes, S., Insalata, F., Kirwan, P., Saei, A., Atti, A., Wellington, E., Khawam, J., Munro, K., Cole, M., et al. (2022) · New England Journal of Medicine · doi:10.1056/nejmoa2118691 · Cited by 711 · see citing works
Pouwels, K. B., Pritchard, E., Matthews, P. C., Stoesser, N., Eyre, D. W., Vihta, K.-D., House, T., Hay, J., Bell, J. I., Newton, J. N., et al. (2021) · doi:10.1101/2021.08.18.21262237 · Cited by 543 · see citing works
Gruell, H., Vanshylla, K., Tober-Lau, P., Hillus, D., Schommers, P., Lehmann, C., Kurth, F., Sander, L. E., & Klein, F. (2022) · Nature Medicine · doi:10.1038/s41591-021-01676-0 · Cited by 410 · see citing works
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McMenamin, M. E., Nealon, J., Lin, Y., Wong, J. Y., Cheung, J. K., Lau, E. H. Y., Wu, P., Leung, G. M., & Cowling, B. J. (2022) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(22)00345-0 · Cited by 360 · see citing works
COVID-19 mRNA vaccines: Platforms and current developments
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Menegale, F., Manica, M., Zardini, A., Guzzetta, G., Marziano, V., d'Andrea, V., Trentini, F., Ajelli, M., Poletti, P., & Merler, S. (2023) · JAMA Network Open · doi:10.1001/jamanetworkopen.2023.10650 · Cited by 280 · see citing works
Ferdinands, J. M., Rao, S., Dixon, B. E., Mitchell, P. K., DeSilva, M. B., Irving, S. A., Lewis, N., Natarajan, K., Stenehjem, E., Grannis, S. J., et al. (2022) · BMJ · doi:10.1136/bmj-2022-072141 · Cited by 185 · see citing works
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Patalon, T., Saciuk, Y., Peretz, A., Perez, G., Lurie, Y., Maor, Y., & Gazit, S. (2022) · Nature Communications · doi:10.1038/s41467-022-30884-6 · Cited by 143 · see citing works
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BackgroundGram, M. A., Emborg, H.-D., Schelde, A. B., Friis, N. U., Nielsen, K. F., Moustsen-Helms, I. R., Legarth, R., Lam, J. U. H., Chaine, M., Malik, A. Z., et al. (2022) · PLOS Medicine · doi:10.1371/journal.pmed.1003992 · Cited by 146 · see citing works
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Patalon, T., Saciuk, Y., Peretz, A., Perez, G., Lurie, Y., Maor, Y., & Gazit, S. (2022) · doi:10.1101/2022.02.25.22271494 · Cited by 143 · see citing works
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Cromer, D., Steain, M., Reynaldi, A., Schlub, T. E., Sasson, S. C., Kent, S. J., Khoury, D. S., & Davenport, M. P. (2022) · doi:10.1101/2022.06.09.22275942 · Cited by 139 · see citing works
Skowronski, D. M., Febriani, Y., Ouakki, M., Setayeshgar, S., El Adam, S., Zou, M., Talbot, D., Prystajecky, N., Tyson, J. R., Gilca, R., et al. (2022) · Clinical Infectious Diseases · doi:10.1093/cid/ciac290 · Cited by 155 · see citing works
Katikireddi, S. V., Cerqueira-Silva, T., Vasileiou, E., Robertson, C., Amele, S., Pan, J., Taylor, B., Boaventura, V., Werneck, G. L., Flores-Ortiz, R., et al. (2022) · The Lancet · doi:10.1016/s0140-6736(21)02754-9 · Cited by 124 · see citing works
Gilboa, M., Regev-Yochay, G., Mandelboim, M., Indenbaum, V., Asraf, K., Fluss, R., Amit, S., Mendelson, E., Doolman, R., Afek, A., et al. (2022) · JAMA Network Open · doi:10.1001/jamanetworkopen.2022.31778 · Cited by 128 · see citing works
Self-citationPersistent B cell memory after SARS-CoV-2 vaccination is functional during breakthrough infections
Terreri, S., Piano Mortari, E., Vinci, M. R., Russo, C., Alteri, C., Albano, C., Colavita, F., Gramigna, G., Agrati, C., Linardos, G., et al. (2022) · Cell Host & Microbe · doi:10.1016/j.chom.2022.01.003 · Cited by 117 · see citing works
Gazit, S., Saciuk, Y., Perez, G., Peretz, A., Pitzer, V. E., & Patalon, T. (2022) · BMJ · doi:10.1136/bmj-2022-071113 · Cited by 87 · see citing works
Waning COVID-19 Vaccine Effectiveness for BNT162b2 and CoronaVac in Malaysia: An Observational Study
Suah, J. L., Husin, M., Tok, P. S. K., Tng, B. H., Thevananthan, T., Low, E. V., Appannan, M. R., Muhamad Zin, F., Mohd Zin, S., Yahaya, H., et al. (2022) · International Journal of Infectious Diseases · doi:10.1016/j.ijid.2022.03.028 · Cited by 76 · see citing works
Long-term immunogenicity of BNT162b2 vaccination in the elderly and in younger health care workers
Tober-Lau, P., Schwarz, T., Vanshylla, K., Hillus, D., Gruell, H., EICOV/COVIM Study Group, Suttorp, N., Landgraf, I., Kappert, K., Seybold, J., et al. (2021) · doi:10.1101/2021.08.26.21262468 · Cited by 69 · see citing works
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Levine-Tiefenbrun, M., Yelin, I., Alapi, H., Herzel, E., Kuint, J., Chodick, G., Gazit, S., Patalon, T., & Kishony, R. (2022) · Nature Communications · doi:10.1038/s41467-022-28936-y · Cited by 63 · see citing works
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Pearson, C. A. B., Silal, S. P., Li, M. W. Z., Dushoff, J., Bolker, B. M., Abbott, S., van Schalkwyk, C., Davies, N. G., Barnard, R. C., Edmunds, W. J., et al. (2021) · doi:10.1101/2021.12.19.21268038 · Cited by 44 · see citing works
Tamandjou Tchuem, C. R., Auvigne, V., Vaux, S., Montagnat, C., Paireau, J., Monnier Besnard, S., Gabet, A., Benhajkassen, N., Le Strat, Y., Parent Du Chatelet, I., et al. (2023) · Vaccine · doi:10.1016/j.vaccine.2023.02.062 · Cited by 27 · see citing works
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Andrejko, K. L., Pry, J. M., Myers, J. F., Mehrotra, M., Lamba, K., Lim, E., Fukui, N., DeGuzman, J. L., Openshaw, J., Watt, J., et al. (2023) · American Journal of Epidemiology · doi:10.1093/aje/kwad017 · Cited by 28 · see citing works
Uwamino, Y., Kurafuji, T., Takato, K., Sakai, A., Tanabe, A., Noguchi, M., Yatabe, Y., Arai, T., Ohno, A., Tomita, Y., et al. (2022) · Vaccine · doi:10.1016/j.vaccine.2022.06.016 · Cited by 21 · see citing works
Arashiro, T., Miwa, M., Nakagawa, H., Takamatsu, J., Oba, K., Fujimi, S., Kikuchi, H., Iwasawa, T., Kanbe, F., Oyama, K., et al. (2024) · Vaccine · doi:10.1016/j.vaccine.2023.12.033 · Cited by 11 · see citing works
- Authors
- Goldberg, Y., Mandel, M., Bar-On, Y. M., Bodenheimer, O., Freedman, L., Haas, E. J., Milo, R., Alroy-Preis, S., Ash, N., & Huppert, A.
- Affiliations
- Tel Aviv University (IL)
- Corresponding author
- Goldberg, Yair
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2021-12-09
- Volume
- 385
- Issue
- 24
- Pages
- e85-e85
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC8609604
- OpenAlex
- W3208466650
- Cited by
- 1,034
- References
- 4
- Citations by year
- 2026: 23 · 2025: 39 · 2024: 100 · 2023: 216 · 2022: 567 · 2021: 88
- FWCI
- 77.04
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- medRxiv (acceptedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Physical Sciences › Mathematics › Modeling and Simulation › COVID-19 epidemiological studies
- Social Sciences › Health › Vaccine Coverage and Hesitancy
- Keywords
- waning immunity, BNT162b2, COVID-19 pandemic, SARS-CoV-2, Delta variant, breakthrough infection, severe COVID-19, vaccine effectiveness, age differences in vaccine response, Israel, mass vaccination campaigns, COVID-19 resurgence, Omicron variant, mRNA vaccines
- MeSH terms
- Immunogenicity, Vaccine, COVID-19, SARS-CoV-2, Vaccine Efficacy, BNT162 Vaccine, Adolescent, Adult, Aged, Antibodies, Viral, Female, Humans, Immunization, Secondary, Israel, Male, Middle Aged, Regression Analysis, Socioeconomic Factors, Time Factors, Poisson Distribution, Antibodies, Neutralizing, Patient Acuity
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