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Waning Effectiveness of the Third Dose of the BNT162b2 mRNA COVID-19 Vaccine
Open accessPreprint — published as 10.1038/s41467-022-30884-6 · Paper page
Abstract
The duration of protection of the third (booster) dose of the BioNTech/Pfizer BNT162b2 mRNA Coronavirus Disease 2019 vaccine has yet to be sufficiently researched, while global discussions around the necessity and effectiveness of a fourth dose are already underway. By conducting a retrospective study implementing a test-negative case-control design, analyzing 546,924 PCR tests performed throughout January 2022 by 389,265 persons who received three doses of the vaccine, we found that the effectiveness in each month since vaccination decreased significantly. Compared to those vaccinated early, on August 2021, relative protection against infection waned from 53.4% a month after vaccination to 16.5% three months after vaccination. These results suggest that there is a significant waning of vaccine effectiveness against the Omicron variant of the third dose of the BNT162b2 vaccine within a few months after administration and should prompt policy discussion as to additional booster doses and vaccine development.
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In the citing paper
“Notwithstanding these limitations, consistent findings were reached, indicating rapid waning of vaccine protection against symptomatic Omicron infection that are consistent with findings of other studies for effectiveness against Omicron infection (with no BA.1/BA.2 subvariant specified)42–48.”
From Duration of mRNA vaccine protection against SARS-CoV-2 Omicron BA.1 and BA.2 subvariants in Qatar (2022) · cites this paper as [45]
In the citing paper
“Nonetheless, compared with the previously demonstrated waning pattern of the relative vaccine effectiveness of three doses versus two doses in real world settings (which begins around three months after inoculation), the relative effectiveness of the fourth dose against infection appears to wane sooner, just as waning after the third dose was sooner than after the second dose.11 26”
In the citing paper
“The waning of vaccine effectiveness against SARS-CoV-2 infection is consistent with previous observations of the second and third doses of the BNT162b2b vaccine.10 11”
In the citing paper
“Therefore, apart from potential scarcity of data in comparing to unvaccinated individuals, this eligible yet unvaccinated population in a massively campaigned environment such as Israel is plausibly different in terms health related behaviour, which could introduce a bias in rendering it the reference group,43 as has been pointed out in previous vaccination studies of Israeli populations measuring”
In the citing paper
“Nonetheless, supporting this design were previous covid-19 studies implementing a test negative design that yielded comparable results to cohort studies on this population,6 11 while presenting diminished bias in the short term outcomes of vaccinee effectiveness.”
In the citing paper
“The lack of pre-defined PCR testing protocols implemented in the study population also presented a challenge. This limitation has been discussed extensively in previous covid-19 observational studies and could lead to potential biases relating to healthcare seeking behaviour.6 11 38 39”
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Citations
Cites
Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine
Polack, F. P., Thomas, S. J., Kitchin, N., Absalon, J., Gurtman, A., Lockhart, S., Perez, J. L., Pérez Marc, G., Moreira, E. D., Zerbini, C., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2034577 · Cited by 14,592
BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting
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Perineuronal nets stabilize the grid cell network
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Waning Immune Humoral Response to BNT162b2 Covid-19 Vaccine over 6 Months
Levin, E. G., Lustig, Y., Cohen, C., Fluss, R., Indenbaum, V., Amit, S., Doolman, R., Asraf, K., Mendelson, E., Ziv, A., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2114583 · Cited by 1,703
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Protection of BNT162b2 Vaccine Booster against Covid-19 in Israel
Bar-On, Y. M., Goldberg, Y., Mandel, M., Bodenheimer, O., Freedman, L., Kalkstein, N., Mizrahi, B., Alroy-Preis, S., Ash, N., Milo, R., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2114255 · Cited by 1,169
Waning Immunity after the BNT162b2 Vaccine in Israel
Goldberg, Y., Mandel, M., Bar-On, Y. M., Bodenheimer, O., Freedman, L., Haas, E. J., Milo, R., Alroy-Preis, S., Ash, N., & Huppert, A. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2114228 · Cited by 1,034
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Research works printed but not linked: 5
- 10.1056/NEJMOA2114114/SUPPL_FILE/NEJMOA2114114_DISCLOSURES.PDF · DOI
- 10.1056/NEJMOA2114583/SUPPL_FILE/NEJMOA2114583_DATA-SHARING.PDF · DOI
- 10.1056/NEJMOA2114228/SUPPL_FILE/NEJMOA2114228_DISCLOSURES.PDF · DOI
- 10.1038/s41467-020-20241-w · DOI · Paper page
- 10.1056/NEJMC2104974/SUPPL_FILE/NEJMC2104974_DISCLOSURES.PDF · DOI
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Metadata
- Authors
- Patalon, T., Saciuk, Y., Peretz, A., Perez, G., Lurie, Y., Maor, Y., & Gazit, S.
- Affiliations
- Maccabi Healthcare Services (IL)
- Shaare Zedek Medical Center (IL)
- Corresponding author
- Patalon, Tal
- Venue
- Nature Communications
- Publisher
- openRxiv
- Published
- 2022-02-26
- Volume
- 13
- Issue
- 1
- Pages
- 3203-3203
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC9184525
- OpenAlex
- W4281648214
- Cited by
- 143
- References
- 23
- Citations by year
- 2026: 4 · 2025: 15 · 2024: 25 · 2023: 56 · 2022: 43
- FWCI
- 16.99
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Nature Communications (publishedVersion, cc-by)
- medRxiv (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Social Sciences › Health › Vaccine Coverage and Hesitancy
- Physical Sciences › Mathematics › Modeling and Simulation › COVID-19 epidemiological studies
- Keywords
- BNT162b2 mRNA vaccine, COVID-19 vaccines, booster vaccination, waning vaccine effectiveness, Omicron variant, COVID-19 pandemic, test-negative case-control, PCR testing, duration of protection
- MeSH terms
- COVID-19, SARS-CoV-2, COVID-19 Vaccines, BNT162 Vaccine, Humans, Retrospective Studies, RNA, Messenger
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