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      Cellular and humoral immune response to SARS-CoV-2 vaccination and booster dose in immunosuppressed patients: An observational cohort study

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          Abstract

          Background

          : Humoral and cellular immune responses to SARS-CoV-2 vaccination among immunosuppressed patients remain poorly defined, as well as variables associated with poor response.

          Methods

          : We performed a retrospective observational cohort study at a large Northern California healthcare system of infection-naïve individuals fully vaccinated against SARS-CoV-2 (mRNA-1273, BNT162b2, or Ad26.COV2.S) with clinical SARS-CoV-2 interferon gamma release assay (IGRA) ordered between January through November 2021. Humoral and cellular immune responses were measured by anti-SARS-CoV-2 S1 IgG ELISA (anti-S1 IgG) and IGRA, respectively, following primary and/or booster vaccination.

          Results

          : 496 immunosuppressed patients (54% female; median age 50 years) were included. 62% (261/419) of patients had positive anti-S1 IgG and 71% (277/389) had positive IGRA after primary vaccination, with 20% of patients having a positive IGRA only. Following booster, 69% (81/118) had positive anti-S1 IgG and 73% (91/124) had positive IGRA. Factors associated with low humoral response rates after primary vaccination included anti-CD20 monoclonal antibodies ( P < 0.001), sphingosine 1-phsophate (S1P) receptor modulators ( P < 0.001), mycophenolate ( P = 0.002), and B cell lymphoma ( P = 0.004); those associated with low cellular response rates included S1P receptor modulators ( P < 0.001) and mycophenolate ( P < 0.001). Of patients who had poor humoral response to primary vaccination, 35% (18/52) developed a significantly higher response after the booster. Only 5% (2/42) of patients developed a significantly higher cellular response to the booster dose compared to primary vaccination.

          Conclusions

          : Humoral and cellular response rates to primary and booster SARS-CoV-2 vaccination differ among immunosuppressed patient groups. Clinical testing of cellular immunity is important in monitoring vaccine response in vulnerable populations.

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          SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls

          Nina Le Bert, Anthony T. Tan, Kamini Kunasegaran … (2020)
          Memory T cells induced by previous pathogens can shape susceptibility to, and the clinical severity of, subsequent infections1. Little is known about the presence in humans of pre-existing memory T cells that have the potential to recognize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we studied T cell responses against the structural (nucleocapsid (N) protein) and non-structural (NSP7 and NSP13 of ORF1) regions of SARS-CoV-2 in individuals convalescing from coronavirus disease 2019 (COVID-19) (n = 36). In all of these individuals, we found CD4 and CD8 T cells that recognized multiple regions of the N protein. Next, we showed that patients (n = 23) who recovered from SARS (the disease associated with SARS-CoV infection) possess long-lasting memory T cells that are reactive to the N protein of SARS-CoV 17 years after the outbreak of SARS in 2003; these T cells displayed robust cross-reactivity to the N protein of SARS-CoV-2. We also detected SARS-CoV-2-specific T cells in individuals with no history of SARS, COVID-19 or contact with individuals who had SARS and/or COVID-19 (n = 37). SARS-CoV-2-specific T cells in uninfected donors exhibited a different pattern of immunodominance, and frequently targeted NSP7 and NSP13 as well as the N protein. Epitope characterization of NSP7-specific T cells showed the recognition of protein fragments that are conserved among animal betacoronaviruses but have low homology to 'common cold' human-associated coronaviruses. Thus, infection with betacoronaviruses induces multi-specific and long-lasting T cell immunity against the structural N protein. Understanding how pre-existing N- and ORF1-specific T cells that are present in the general population affect the susceptibility to and pathogenesis of SARS-CoV-2 infection is important for the management of the current COVID-19 pandemic.
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            Waning Immune Humoral Response to BNT162b2 Covid-19 Vaccine over 6 Months

            Einav Levin, Yaniv Lustig, Carmit Cohen … (2021)
            Background Despite high vaccine coverage and effectiveness, the incidence of symptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been increasing in Israel. Whether the increasing incidence of infection is due to waning immunity after the receipt of two doses of the BNT162b2 vaccine is unclear. Methods We conducted a 6-month longitudinal prospective study involving vaccinated health care workers who were tested monthly for the presence of anti-spike IgG and neutralizing antibodies. Linear mixed models were used to assess the dynamics of antibody levels and to determine predictors of antibody levels at 6 months. Results The study included 4868 participants, with 3808 being included in the linear mixed-model analyses. The level of IgG antibodies decreased at a consistent rate, whereas the neutralizing antibody level decreased rapidly for the first 3 months with a relatively slow decrease thereafter. Although IgG antibody levels were highly correlated with neutralizing antibody titers (Spearman’s rank correlation between 0.68 and 0.75), the regression relationship between the IgG and neutralizing antibody levels depended on the time since receipt of the second vaccine dose. Six months after receipt of the second dose, neutralizing antibody titers were substantially lower among men than among women (ratio of means, 0.64; 95% confidence interval [CI], 0.55 to 0.75), lower among persons 65 years of age or older than among those 18 to less than 45 years of age (ratio of means, 0.58; 95% CI, 0.48 to 0.70), and lower among participants with immunosuppression than among those without immunosuppression (ratio of means, 0.30; 95% CI, 0.20 to 0.46). Conclusions Six months after receipt of the second dose of the BNT162b2 vaccine, humoral response was substantially decreased, especially among men, among persons 65 years of age or older, and among persons with immunosuppression.
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              Antibody Response to 2-Dose SARS-CoV-2 mRNA Vaccine Series in Solid Organ Transplant Recipients

              Brian J Boyarsky, William A Werbel, Robin K Avery … (2021)
              Article 0 comments Cited 525 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Clin Virol
                Journal ID (iso-abbrev): J Clin Virol
                Title: Journal of Clinical Virology
                Publisher: Elsevier B.V.
                ISSN (Print): 1386-6532
                ISSN (Electronic): 1873-5967
                Publication date PMC-release: 11 June 2022
                Publication date (Print): August 2022
                Publication date (Electronic): 11 June 2022
                Volume: 153
                Page: 105217
                Affiliations
                [a ]Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305 United States of America
                [b ]Department of Medicine, Division of Oncology, Stanford University School of Medicine, Stanford, CA 94305 United States of America
                [c ]Sean N. Parker Center for Allergy & Asthma Research, Stanford, CA 94305 United States of America
                [d ]Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, CA 94305 United States of America
                [e ]Department of Medicine, Division of Pulmonary, Allergy & Critical Care Medicine, Stanford University School of Medicine, Stanford, CA 94305 United States of America
                [f ]Department of Pediatrics, Division of Pediatric Infectious Diseases, Stanford University School of Medicine, Stanford CA 94305 United States of America
                [g ]Department of Medicine, Division of Nephrology, Stanford University School of Medicine, Stanford, CA 94305 United States of America
                [h ]Department of Surgery, Division of Abdominal Transplantation, Stanford University School of Medicine, Stanford, CA 94305 United States of America
                [i ]Clinical Microbiology Laboratory, Stanford Health Care, Palo Alto, CA 94304 United States of America
                Author notes
                [* ]Corresponding author at: 3375 Hillview Ave Rm 1602, Palo Alto, CA 94304 United States of America
                [1]

                These authors contributed equally

                Article
                Publisher Item ID: S1386-6532(22)00150-0 Publisher ID: 105217
                DOI: 10.1016/j.jcv.2022.105217
                PMC ID: 9188451
                PubMed ID: 35714462
                SO-VID: cb4da967-9b5e-4b24-8177-045502ea8ee9
                Copyright © © 2022 Elsevier B.V. All rights reserved.
                License:

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                Date received : 9 February 2022
                Date revision received : 3 June 2022
                Date accepted : 10 June 2022
                Categories
                Subject: Article

                ScienceOpen disciplines: Microbiology & Virology
                Keywords: covid-19,sars-cov-2,vaccination,igra,serology,immunosuppression
                Data availability:
                ScienceOpen disciplines: Microbiology & Virology
                Keywords: covid-19, sars-cov-2, vaccination, igra, serology, immunosuppression

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