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Effectiveness of mRNA-1273 vaccination against SARS-CoV-2 omicron subvariants BA.1, BA.2, BA.2.12.1, BA.4, and BA.5

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Tseng, Hung Fu, Ackerson, Bradley K., Bruxvoort, Katia J., Sy, Lina S., Tubert, Julia E., Lee, Gina S., Ku, Jennifer H., Florea, Ana, Luo, Yi, Qiu, Sijia, Choi, Soon Kyu, Takhar, Harpreet S., Aragones, Michael, Paila, Yamuna D., Chavers, Scott, Talarico, Carla A., Qian, Lei·2023·Nature Communications

DOI 10.1038/s41467-023-35815-7PMC PMC9836332

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Abstract

Studies have reported reduced natural SARS-CoV-2 infection- and vaccine-induced neutralization against omicron BA.4/BA.5 compared with earlier omicron subvariants. This test-negative case-control study evaluates mRNA-1273 vaccine effectiveness (VE) against infection and hospitalization with omicron subvariants. The study includes 30,809 SARS-CoV-2 positive and 92,427 SARS-CoV-2 negative individuals aged ≥18 years tested during 1/1/2022-6/30/2022. While 3-dose VE against BA.1 infection is high and wanes slowly, VE against BA.2, BA.2.12.1, BA.4, and BA.5 infection is initially moderate to high (61.0%-90.6% 14-30 days post third dose) and wanes rapidly. The 4-dose VE against infection with BA.2, BA.2.12.1, and BA.4 ranges between 64.3%-75.7%, and is low (30.8%) against BA.5 14-30 days post fourth dose, disappearing beyond 90 days for all subvariants. The 3-dose VE against hospitalization for BA.1, BA.2, and BA.4/BA.5 is 97.5%, 82.0%, and 72.4%, respectively; 4-dose VE against hospitalization for BA.4/BA.5 is 88.5%. Evaluation of the updated bivalent booster is warranted.

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Fig. 1 Flow chart for mRNA-1273 vaccine test-negative design. (N = 123,236). Steps for selection of 30,809 cases and 92,427 controls by inclusion and exclusion criteria, and subsequent matching for vaccine effectiveness estimation. COVID-19 coronavirus disease; KPSC Kaiser Permanente Southern California.CC BY · PubMed Central

Fig. 2 Adjusted vaccine effectiveness (VE) and relative vaccine effectiveness (rVE) of mRNA-1273 against infection with omicron subvariants by time since 3rd dose vaccination. Adjusted VE of three doses of mRNA-1273 and adjusted rVE of three versus two doses of mRNA-1273 and their 95% confidence intervals against infection with SARS-CoV-2 omicron subvariants. Sample size for each analysis equals the number of three-dose vaccinated divided by the percentage of three-dose vaccinated. Symbols represent the adjusted vaccine effectiveness or adjusted relative vaccine effectiveness. aWhen the OR or its 95% CI was >1, the VE/rVE or its 95% CI was transformed as ([1/OR] – 1) × 100. bAdjusted for age, sex, race/ethnicity, month of specimen collection, history of SARS-CoV-2 infection, history of SARS-CoV-2 molecular test, number of outpatient and virtual visits, medical center area, and time between second dose and specimen collection date (for three-dose versus two-dose models only). cMedical center area removed from adjustment set in three-dose versus two-dose models due to lack of model convergence. dBA.2 excluding BA.2.12.1. eMedical center area removed from adjustment set in three-dose versus unvaccinated models due to lack of model convergence. CI confidence interval, OR odds ratio, rVE relative vaccine effectiveness, VE vaccine effectiveness.CC BY · PubMed Central

Fig. 3 Adjusted vaccine effectiveness (VE) and relative vaccine effectiveness (rVE) of mRNA-1273 against infection with omicron subvariants by time since 4th dose vaccination. Adjusted VE of four doses of mRNA-1273 and adjusted rVE of four versus three doses of mRNA-1273 and their 95% confidence intervals against infection with SARS-CoV-2 omicron subvariants. Sample size for each analysis equals the number of four-dose vaccinated divided by the percentage of four-dose vaccinated. Symbols represent the adjusted vaccine effectiveness or adjusted relative vaccine effectiveness. aWhen the OR or its 95% CI was >1, the VE/rVE or its 95% CI was transformed as ([1/OR] – 1) × 100. bAdjusted for age, sex, race/ethnicity, month of specimen collection, history of SARS-CoV-2 infection, history of SARS-CoV-2 molecular test, number of outpatient and virtual visits, medical center area, and time between third dose and specimen collection date (for four-dose versus three-dose models only). cBA.2 excluding BA.2.12.1. dMedical center area removed from adjustment set in four-dose versus three-dose models due to lack of model convergence. eMedical center area removed from adjustment set in four-dose versus unvaccinated models due to lack of model convergence. CI confidence interval, OR odds ratio, rVE relative vaccine effectiveness, VE vaccine effectiveness.CC BY · PubMed Central

Fig. 4 Adjusted vaccine effectiveness (VE) and relative vaccine effectiveness (rVE) of mRNA-1273 against hospitalization for omicron subvariants by time since 3rd or 4th dose vaccination. Adjusted VE of 3 and four doses of mRNA-1273 and adjusted rVE of 3 versus two doses and 4 versus three doses of mRNA-1273 and their 95% confidence intervals against hospitalization for SARS-CoV-2 omicron subvariants. Sample size for each analysis equals the number of three-dose vaccinated divided by the percentage of three-dose vaccinated for the three-dose models, and is equal to the number of four-dose vaccinated divided by the percentage of four-dose vaccinated for the four-dose models. aAdjusted for age, sex, race/ethnicity, month of specimen collection, history of SARS-CoV-2 infection, history of SARS-CoV-2 molecular test, number of outpatient and virtual visits, and time between second/third dose and specimen collection date (for three-dose versus two-dose and four-dose versus three-dose models, respectively). Medical center area dropped from adjustment set due to lack of model convergence. Symbols represent the adjusted vaccine effectiveness or adjusted relative vaccine effectiveness. bWhen the OR or its 95% CI was >1, the VE/rVE or its 95% CI was transformed as ([1/OR] – 1) × 100. cHistory of SARS-CoV-2 infection dropped from adjustment set in four-dose versus three-dose models due to lack of model convergence. CI confidence interval, OR odds ratio, rVE relative vaccine effectiveness, VE vaccine effectiveness.CC BY · PubMed Central

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Authors: Tseng, H. F., Ackerson, B. K., Bruxvoort, K. J., Sy, L. S., Tubert, J. E., Lee, G. S., Ku, J. H., Florea, A., Luo, Y., Qiu, S., Choi, S. K., Takhar, H. S., Aragones, M., Paila, Y. D., Chavers, S., Talarico, C. A., & Qian, L.
Affiliations: Kaiser Permanente (US)
AstraZeneca (United States) (US)
Corresponding author: Tseng, Hung Fu
ORCID: Tseng, Hung Fu
Ackerson, Bradley K.
Bruxvoort, Katia J.
Sy, Lina S.
Tubert, Julia E.
Lee, Gina S.
Ku, Jennifer H.
Florea, Ana
Luo, Yi
Qiu, Sijia
Choi, Soon Kyu
Takhar, Harpreet S.
Talarico, Carla A.
Qian, Lei
Venue: Nature Communications
Publisher: Springer Science and Business Media LLC
Published: 2023-01-12
Volume: 14
Issue: 1
Pages: 189-189
ISSN: 2041-1723 (ISSN-L)
DOI: 10.1038/s41467-023-35815-7
PMC: PMC9836332
OpenAlex: W4315779712
Cited by: 105
References: 44
Citations by year: 2026: 5 · 2025: 18 · 2024: 33 · 2023: 46
FWCI: 20.99
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0 (tdm)
creativecommons.org/licenses/by/4.0 (vor)
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, cc-by-sa)
Funders: Moderna, Inc.
Topics: Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
Physical Sciences › Mathematics › Modeling and Simulation › COVID-19 epidemiological studies
Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
Keywords: mRNA-1273 vaccine, SARS-CoV-2 Omicron subvariants, vaccine effectiveness, BA.1, BA.2, BA.2.12.1, BA.4, BA.5, COVID-19 infection, hospitalization, waning immunity, bivalent booster, neutralizing antibodies
MeSH terms: COVID-19, SARS-CoV-2, 2019-nCoV Vaccine mRNA-1273, Adolescent, Adult, Humans, Vaccination, Case-Control Studies

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Effectiveness of mRNA-1273 vaccination against SARS-CoV-2 omicron subvariants BA.1, BA.2, BA.2.12.1, BA.4, and BA.5

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