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Enhanced virulence and waning vaccine-elicited antibodies account for breakthrough infections caused by SARS-CoV-2 delta and beyond.
Kwon, Hyung-Joon; Kosikova, Martina; Tang, Weichun; Ortega-Rodriguez, Uriel; Radvak, Peter; Xiang, Ruoxuan; Mercer, Kelly E; Muskhelishvili, Levan; Davis, Kelly; Ward, Jerrold M; Kosik, Ivan; Holly, Jaroslav; Kang, Insung; Yewdell, Jonathan W; Plant, Ewan P; Chen, Wilbur H; Shriver, Mallory C; Barnes, Robin S; Pasetti, Marcela F; Zhou, Bin; Wentworth, David E; Xie, Hang.
  • Kwon HJ; Laboratory of Pediatric and Respiratory Viral Diseases, Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, USA.
  • Kosikova M; Laboratory of Pediatric and Respiratory Viral Diseases, Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, USA.
  • Tang W; Laboratory of Pediatric and Respiratory Viral Diseases, Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, USA.
  • Ortega-Rodriguez U; Laboratory of Pediatric and Respiratory Viral Diseases, Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, USA.
  • Radvak P; Laboratory of Pediatric and Respiratory Viral Diseases, Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, USA.
  • Xiang R; Division of Biostatistics, Office of Biostatistics and Epidemiology, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, USA.
  • Mercer KE; Biomarkers and Alternative Models Branch, National Center for Toxicological Research, United States Food and Drug Administration, Jefferson, AR, USA.
  • Muskhelishvili L; Toxicologic Pathology Associates, Jefferson, AR, USA.
  • Davis K; Toxicologic Pathology Associates, Jefferson, AR, USA.
  • Ward JM; Global VetPathology, Montgomery Village, MD, USA.
  • Kosik I; Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Holly J; Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Kang I; Laboratory of Pediatric and Respiratory Viral Diseases, Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, USA.
  • Yewdell JW; Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Plant EP; Laboratory of Pediatric and Respiratory Viral Diseases, Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, USA.
  • Chen WH; Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA.
  • Shriver MC; Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA.
  • Barnes RS; Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA.
  • Pasetti MF; Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA.
  • Zhou B; CDC COVID-19 Response, Centers for Disease Control and Prevention, Atlanta, GA, USA.
  • Wentworth DE; CDC COVID-19 Response, Centers for Disease Control and Prevention, Atlanta, GA, USA.
  • Xie H; Laboratory of Pediatric and Respiratory Viral Diseases, Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, USA.
iScience ; 25(12): 105507, 2022 Dec 22.
Article in English | MEDLINE | ID: covidwho-2095533
ABSTRACT
Here we interrogate the factors responsible for SARS-CoV-2 breakthrough infections in a K18-hACE2 transgenic mouse model. We show that Delta and the closely related Kappa variant cause viral pneumonia and severe lung lesions in K18-hACE2 mice. Human COVID-19 mRNA post-vaccination sera after the 2nd dose are significantly less efficient in neutralizing Delta/Kappa than early 614G virus in vitro and in vivo. By 5 months post-vaccination, ≥50% of donors lack detectable neutralizing antibodies against Delta and Kappa and all mice receiving 5-month post-vaccination sera die after the lethal challenges. Although a 3rd vaccine dose can boost antibody neutralization against Delta in vitro and in vivo, the mean log neutralization titers against the latest Omicron subvariants are 1/3-1/2 of those against the original 614D virus. Our results suggest that enhanced virulence, greater immune evasion, and waning of vaccine-elicited protection account for SARS-CoV-2 variants caused breakthrough infections.
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Full text: Available Collection: International databases Database: MEDLINE Topics: Vaccines / Variants Language: English Journal: IScience Year: 2022 Document Type: Article Affiliation country: J.isci.2022.105507

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Full text: Available Collection: International databases Database: MEDLINE Topics: Vaccines / Variants Language: English Journal: IScience Year: 2022 Document Type: Article Affiliation country: J.isci.2022.105507