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Persistent SARS-CoV-2-specific immune defects in kidney transplant recipients following third mRNA vaccine dose.
Werbel, William A; Karaba, Andrew H; Chiang, Teresa Po-Yu; Massie, Allan B; Brown, Diane M; Watson, Natasha; Chahoud, Maggie; Thompson, Elizabeth A; Johnson, Aileen C; Avery, Robin K; Cochran, Willa V; Warren, Daniel; Liang, Tao; Fribourg, Miguel; Huerta, Christopher; Samaha, Hady; Klein, Sabra L; Bettinotti, Maria P; Clarke, William A; Sitaras, Ioannis; Rouphael, Nadine; Cox, Andrea L; Bailey, Justin R; Pekosz, Andrew; Tobian, Aaron A R; Durand, Christine M; Bridges, Nancy D; Larsen, Christian P; Heeger, Peter S; Segev, Dorry L.
  • Werbel WA; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. Electronic address: wwerbel1@jhmi.edu.
  • Karaba AH; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Chiang TP; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Massie AB; Department of Surgery, New York University Grossman School of Medicine, New York, New York, USA; Department of Population Health, New York University Grossman School of Medicine, New York, New York, USA.
  • Brown DM; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Watson N; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Chahoud M; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Thompson EA; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Johnson AC; Department of Surgery, Emory University, Atlanta, Georgia, USA.
  • Avery RK; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Cochran WV; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Warren D; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Liang T; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Fribourg M; Translational Transplant Research Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Huerta C; Department of Medicine, Emory University, Atlanta, Georgia, USA.
  • Samaha H; Department of Medicine, Emory University, Atlanta, Georgia, USA.
  • Klein SL; Department of Medicine, Emory University, Atlanta, Georgia, USA.
  • Bettinotti MP; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Clarke WA; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Sitaras I; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
  • Rouphael N; Department of Medicine, Emory University, Atlanta, Georgia, USA.
  • Cox AL; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Department of Medicine, Emory University, Atlanta, Georgia, USA; Bloomberg Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Bailey JR; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Pekosz A; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
  • Tobian AAR; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Durand CM; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Bridges ND; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Larsen CP; Department of Surgery, Emory University, Atlanta, Georgia, USA.
  • Heeger PS; Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
  • Segev DL; Department of Surgery, New York University Grossman School of Medicine, New York, New York, USA; Department of Population Health, New York University Grossman School of Medicine, New York, New York, USA.
Am J Transplant ; 23(6): 744-758, 2023 06.
Article in English | MEDLINE | ID: covidwho-2286568
ABSTRACT
Kidney transplant recipients (KTRs) show poorer response to SARS-CoV-2 mRNA vaccination, yet response patterns and mechanistic drivers following third doses are ill-defined. We administered third monovalent mRNA vaccines to n = 81 KTRs with negative or low-titer anti-receptor binding domain (RBD) antibody (n = 39 anti-RBDNEG; n = 42 anti-RBDLO), compared with healthy controls (HCs, n = 19), measuring anti-RBD, Omicron neutralization, spike-specific CD8+%, and SARS-CoV-2-reactive T cell receptor (TCR) repertoires. By day 30, 44% anti-RBDNEG remained seronegative; 5% KTRs developed BA.5 neutralization (vs 68% HCs, P < .001). Day 30 spike-specific CD8+% was negative in 91% KTRs (vs 20% HCs; P = .07), without correlation to anti-RBD (rs = 0.17). Day 30 SARS-CoV-2-reactive TCR repertoires were detected in 52% KTRs vs 74% HCs (P = .11). Spike-specific CD4+ TCR expansion was similar between KTRs and HCs, yet KTR CD8+ TCR depth was 7.6-fold lower (P = .001). Global negative response was seen in 7% KTRs, associated with high-dose MMF (P = .037); 44% showed global positive response. Of the KTRs, 16% experienced breakthrough infections, with 2 hospitalizations; prebreakthrough variant neutralization was poor. Absent neutralizing and CD8+ responses in KTRs indicate vulnerability to COVID-19 despite 3-dose mRNA vaccination. Lack of neutralization despite CD4+ expansion suggests B cell dysfunction and/or ineffective T cell help. Development of more effective KTR vaccine strategies is critical. (NCT04969263).
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Kidney Transplantation / COVID-19 Type of study: Observational study Topics: Vaccines / Variants Limits: Humans Language: English Journal: Am J Transplant Journal subject: Transplantation Year: 2023 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Kidney Transplantation / COVID-19 Type of study: Observational study Topics: Vaccines / Variants Limits: Humans Language: English Journal: Am J Transplant Journal subject: Transplantation Year: 2023 Document Type: Article