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Vaccine Breakthrough Infections with SARS-CoV-2 Variants.
N Engl J Med. 2021 06 10; 384(23):2212-2218.NEJM

Abstract

Emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are of clinical concern. In a cohort of 417 persons who had received the second dose of BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine at least 2 weeks previously, we identified 2 women with vaccine breakthrough infection. Despite evidence of vaccine efficacy in both women, symptoms of coronavirus disease 2019 developed, and they tested positive for SARS-CoV-2 by polymerase-chain-reaction testing. Viral sequencing revealed variants of likely clinical importance, including E484K in 1 woman and three mutations (T95I, del142-144, and D614G) in both. These observations indicate a potential risk of illness after successful vaccination and subsequent infection with variant virus, and they provide support for continued efforts to prevent and diagnose infection and to characterize variants in vaccinated persons. (Funded by the National Institutes of Health and others.).

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Authors+Show Affiliations

Hacisuleyman E
From the Laboratory of Molecular Neuro-oncology (E.H., C.H., Y.S., N.E.B., M.B., E.G.C., R.B.D.), the Laboratory of Molecular Immunology (D.J.S.-B., C.G., M.C.N.), the Laboratory of Human Genetics and Genomics (R.L.), the Laboratory of Retrovirology (J.D., F.M., T.H., P.D.B.), and the Howard Hughes Medical Institute (M.C.N., P.D.B., R.B.D.), Rockefeller University, New York.
Hale C
From the Laboratory of Molecular Neuro-oncology (E.H., C.H., Y.S., N.E.B., M.B., E.G.C., R.B.D.), the Laboratory of Molecular Immunology (D.J.S.-B., C.G., M.C.N.), the Laboratory of Human Genetics and Genomics (R.L.), the Laboratory of Retrovirology (J.D., F.M., T.H., P.D.B.), and the Howard Hughes Medical Institute (M.C.N., P.D.B., R.B.D.), Rockefeller University, New York.
Saito Y
From the Laboratory of Molecular Neuro-oncology (E.H., C.H., Y.S., N.E.B., M.B., E.G.C., R.B.D.), the Laboratory of Molecular Immunology (D.J.S.-B., C.G., M.C.N.), the Laboratory of Human Genetics and Genomics (R.L.), the Laboratory of Retrovirology (J.D., F.M., T.H., P.D.B.), and the Howard Hughes Medical Institute (M.C.N., P.D.B., R.B.D.), Rockefeller University, New York.
Blachere NE
From the Laboratory of Molecular Neuro-oncology (E.H., C.H., Y.S., N.E.B., M.B., E.G.C., R.B.D.), the Laboratory of Molecular Immunology (D.J.S.-B., C.G., M.C.N.), the Laboratory of Human Genetics and Genomics (R.L.), the Laboratory of Retrovirology (J.D., F.M., T.H., P.D.B.), and the Howard Hughes Medical Institute (M.C.N., P.D.B., R.B.D.), Rockefeller University, New York.
Bergh M
From the Laboratory of Molecular Neuro-oncology (E.H., C.H., Y.S., N.E.B., M.B., E.G.C., R.B.D.), the Laboratory of Molecular Immunology (D.J.S.-B., C.G., M.C.N.), the Laboratory of Human Genetics and Genomics (R.L.), the Laboratory of Retrovirology (J.D., F.M., T.H., P.D.B.), and the Howard Hughes Medical Institute (M.C.N., P.D.B., R.B.D.), Rockefeller University, New York.
Conlon EG
From the Laboratory of Molecular Neuro-oncology (E.H., C.H., Y.S., N.E.B., M.B., E.G.C., R.B.D.), the Laboratory of Molecular Immunology (D.J.S.-B., C.G., M.C.N.), the Laboratory of Human Genetics and Genomics (R.L.), the Laboratory of Retrovirology (J.D., F.M., T.H., P.D.B.), and the Howard Hughes Medical Institute (M.C.N., P.D.B., R.B.D.), Rockefeller University, New York.
Schaefer-Babajew DJ
From the Laboratory of Molecular Neuro-oncology (E.H., C.H., Y.S., N.E.B., M.B., E.G.C., R.B.D.), the Laboratory of Molecular Immunology (D.J.S.-B., C.G., M.C.N.), the Laboratory of Human Genetics and Genomics (R.L.), the Laboratory of Retrovirology (J.D., F.M., T.H., P.D.B.), and the Howard Hughes Medical Institute (M.C.N., P.D.B., R.B.D.), Rockefeller University, New York.
DaSilva J
From the Laboratory of Molecular Neuro-oncology (E.H., C.H., Y.S., N.E.B., M.B., E.G.C., R.B.D.), the Laboratory of Molecular Immunology (D.J.S.-B., C.G., M.C.N.), the Laboratory of Human Genetics and Genomics (R.L.), the Laboratory of Retrovirology (J.D., F.M., T.H., P.D.B.), and the Howard Hughes Medical Institute (M.C.N., P.D.B., R.B.D.), Rockefeller University, New York.
Muecksch F
From the Laboratory of Molecular Neuro-oncology (E.H., C.H., Y.S., N.E.B., M.B., E.G.C., R.B.D.), the Laboratory of Molecular Immunology (D.J.S.-B., C.G., M.C.N.), the Laboratory of Human Genetics and Genomics (R.L.), the Laboratory of Retrovirology (J.D., F.M., T.H., P.D.B.), and the Howard Hughes Medical Institute (M.C.N., P.D.B., R.B.D.), Rockefeller University, New York.
Gaebler C
From the Laboratory of Molecular Neuro-oncology (E.H., C.H., Y.S., N.E.B., M.B., E.G.C., R.B.D.), the Laboratory of Molecular Immunology (D.J.S.-B., C.G., M.C.N.), the Laboratory of Human Genetics and Genomics (R.L.), the Laboratory of Retrovirology (J.D., F.M., T.H., P.D.B.), and the Howard Hughes Medical Institute (M.C.N., P.D.B., R.B.D.), Rockefeller University, New York.
Lifton R
From the Laboratory of Molecular Neuro-oncology (E.H., C.H., Y.S., N.E.B., M.B., E.G.C., R.B.D.), the Laboratory of Molecular Immunology (D.J.S.-B., C.G., M.C.N.), the Laboratory of Human Genetics and Genomics (R.L.), the Laboratory of Retrovirology (J.D., F.M., T.H., P.D.B.), and the Howard Hughes Medical Institute (M.C.N., P.D.B., R.B.D.), Rockefeller University, New York.
Nussenzweig MC
From the Laboratory of Molecular Neuro-oncology (E.H., C.H., Y.S., N.E.B., M.B., E.G.C., R.B.D.), the Laboratory of Molecular Immunology (D.J.S.-B., C.G., M.C.N.), the Laboratory of Human Genetics and Genomics (R.L.), the Laboratory of Retrovirology (J.D., F.M., T.H., P.D.B.), and the Howard Hughes Medical Institute (M.C.N., P.D.B., R.B.D.), Rockefeller University, New York.
Hatziioannou T
From the Laboratory of Molecular Neuro-oncology (E.H., C.H., Y.S., N.E.B., M.B., E.G.C., R.B.D.), the Laboratory of Molecular Immunology (D.J.S.-B., C.G., M.C.N.), the Laboratory of Human Genetics and Genomics (R.L.), the Laboratory of Retrovirology (J.D., F.M., T.H., P.D.B.), and the Howard Hughes Medical Institute (M.C.N., P.D.B., R.B.D.), Rockefeller University, New York.
Bieniasz PD
From the Laboratory of Molecular Neuro-oncology (E.H., C.H., Y.S., N.E.B., M.B., E.G.C., R.B.D.), the Laboratory of Molecular Immunology (D.J.S.-B., C.G., M.C.N.), the Laboratory of Human Genetics and Genomics (R.L.), the Laboratory of Retrovirology (J.D., F.M., T.H., P.D.B.), and the Howard Hughes Medical Institute (M.C.N., P.D.B., R.B.D.), Rockefeller University, New York.
Darnell RB
From the Laboratory of Molecular Neuro-oncology (E.H., C.H., Y.S., N.E.B., M.B., E.G.C., R.B.D.), the Laboratory of Molecular Immunology (D.J.S.-B., C.G., M.C.N.), the Laboratory of Human Genetics and Genomics (R.L.), the Laboratory of Retrovirology (J.D., F.M., T.H., P.D.B.), and the Howard Hughes Medical Institute (M.C.N., P.D.B., R.B.D.), Rockefeller University, New York.

MeSH

2019-nCoV Vaccine mRNA-1273AgedAntibodies, NeutralizingAntibodies, ViralBNT162 VaccineCOVID-19COVID-19 VaccinesFemaleHumansMiddle AgedMutationNeutralization TestsPhylogenyPolymerase Chain ReactionSARS-CoV-2Sequence Analysis, RNASpike Glycoprotein, CoronavirusViral Load

Pub Type(s)

Case Reports
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33882219

Clinical Trial Links

Phase II Study of AVX/COVID-12 Vaccine in Subjects With Prior SARS-CoV-2 Immunity Evidence

Citation

Hacisuleyman, Ezgi, et al. "Vaccine Breakthrough Infections With SARS-CoV-2 Variants." The New England Journal of Medicine, vol. 384, no. 23, 2021, pp. 2212-2218.
Hacisuleyman E, Hale C, Saito Y, et al. Vaccine Breakthrough Infections with SARS-CoV-2 Variants. N Engl J Med. 2021;384(23):2212-2218.
Hacisuleyman, E., Hale, C., Saito, Y., Blachere, N. E., Bergh, M., Conlon, E. G., Schaefer-Babajew, D. J., DaSilva, J., Muecksch, F., Gaebler, C., Lifton, R., Nussenzweig, M. C., Hatziioannou, T., Bieniasz, P. D., & Darnell, R. B. (2021). Vaccine Breakthrough Infections with SARS-CoV-2 Variants. The New England Journal of Medicine, 384(23), 2212-2218. https://doi.org/10.1056/NEJMoa2105000
Hacisuleyman E, et al. Vaccine Breakthrough Infections With SARS-CoV-2 Variants. N Engl J Med. 2021 06 10;384(23):2212-2218. PubMed PMID: 33882219.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vaccine Breakthrough Infections with SARS-CoV-2 Variants. AU - Hacisuleyman,Ezgi, AU - Hale,Caryn, AU - Saito,Yuhki, AU - Blachere,Nathalie E, AU - Bergh,Marissa, AU - Conlon,Erin G, AU - Schaefer-Babajew,Dennis J, AU - DaSilva,Justin, AU - Muecksch,Frauke, AU - Gaebler,Christian, AU - Lifton,Richard, AU - Nussenzweig,Michel C, AU - Hatziioannou,Theodora, AU - Bieniasz,Paul D, AU - Darnell,Robert B, Y1 - 2021/04/21/ PY - 2021/4/22/pubmed PY - 2021/6/17/medline PY - 2021/4/21/entrez SP - 2212 EP - 2218 JF - The New England journal of medicine JO - N Engl J Med VL - 384 IS - 23 N2 - Emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are of clinical concern. In a cohort of 417 persons who had received the second dose of BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine at least 2 weeks previously, we identified 2 women with vaccine breakthrough infection. Despite evidence of vaccine efficacy in both women, symptoms of coronavirus disease 2019 developed, and they tested positive for SARS-CoV-2 by polymerase-chain-reaction testing. Viral sequencing revealed variants of likely clinical importance, including E484K in 1 woman and three mutations (T95I, del142-144, and D614G) in both. These observations indicate a potential risk of illness after successful vaccination and subsequent infection with variant virus, and they provide support for continued efforts to prevent and diagnose infection and to characterize variants in vaccinated persons. (Funded by the National Institutes of Health and others.). SN - 1533-4406 UR - https://www.unboundmedicine.com/medline/citation/33882219/Vaccine_Breakthrough_Infections_with_SARS_CoV_2_Variants_ DB - PRIME DP - Unbound Medicine ER -