The Journal of Clinical Investigation最新文献

{"title":"Neutralizing activity of anti–SARS-CoV-2 hyperimmune immunoglobulins and intravenous immunoglobulins against currently circulating SARS-CoV-2 variants","authors":"Lorenza Bellusci, Hana Golding, Surender Khurana","doi":"10.1172/jci182919","DOIUrl":"https://doi.org/10.1172/jci182919","url":null,"abstract":"<p><b>To the Editor:</b> Prophylactic or early post-exposure treatments with SARS-CoV-2–specific monoclonal antibodies (mAbs) were useful early in the COVID-19 pandemic. However, the currently circulating SARS-CoV-2 Omicron subvariants (e.g., XBB.1, JN.1 and its derivatives) are resistant to all approved mAb therapies (<span>1</span>). Immunoglobulin products (IGs) manufactured from pooled human plasma are widely used for treatment of patients with several immunodeficiency syndromes. Most IGs are administered intravenously and are called IVIGs.</p>\u0000<p>Polyclonal hyperimmune anti–SARS-CoV-2 IVIGs (pi-hCoV-2IG) were manufactured in 2021 by fractionation of pooled plasma from COVID-19 convalescent patients with virus neutralization titers of 1:320 or greater against the ancestral WA-1 strain and contain IgG at 10-fold higher concentration than in individual convalescent plasma (CP). Vx-hCoV-2IG was generated from pooled plasma of SARS-CoV-2–vaccinated individuals (2021) (<span>2</span>). Some vaccinated individuals also reported prior SARS-CoV-2 infection. Since 2022, more than 90% of the blood donations in the United States had anti–SARS-CoV-2 antibodies, suggesting prior exposure by vaccination, infections, or both (hybrid immunity) (<span><span></span>3</span>). Therefore, we hypothesized that IVIG lots manufactured from unscreened plasma donors from 2022 onwards may contain anti–SARS-CoV-2 neutralizing antibodies against circulating Omicron subvariants.</p>\u0000<p>To evaluate therapeutic potential of multiple lots of IVIG, pi-hCoV-2IG, and Vx-hCoV-2IG against circulating Omicron variants (Supplemental Table 1; supplemental material available online with this article; https://doi.org/10.1172/JCI182919DS1), we followed the STROBE reporting guideline (https://www.strobe-statement.org/) for cross-sectional studies. We tested 17 lots of pi-hCoV-2IG prepared from pooled plasma of convalescent individuals infected with SARS-CoV-2 in 2020 and one available Vx-hCoV-2IG lot manufactured from screened pooled plasma with high SARS-CoV-2 neutralization titers of mRNA-vaccinated individuals (hybrid immunity) who reported prior SARS-CoV-2 infection in 2021. Additionally, 20 IVIG preparations manufactured in 2019 from healthy plasma donations (2019-IVIG) before the COVID-19 pandemic, 8 IVIG lots manufactured in 2020 (2020-IVIG), 9 IVIG lots manufactured in 2023 (2023-IVIG), 5 IVIG lots manufactured in 2024 (2024-IVIG), 7 CP from recovered COVID-19 patients in early 2020 (2020-CP), and 8 CP from Omicron vaccine breakthrough infections in 2022 (2022-CP), all collected approximately 30 days after diagnosis, were analyzed for neutralization of SARS-CoV-2 WA-1 and 9 circulating Omicron subvariants (BA.2.86, XBB.1.16, XBB.2.3, EG.5, HV.1, HK.3, JN.1, JN.4, and JD.1.1) in a pseudovirus neutralization assay (PsVNA) (<span>4</span>).</p>\u0000<p>CP collected from recovered COVID-19 patients in 2020 and 2022 as well post-infection hyperimmunoglobulin lots (pi-hCoV-2IG) show high ","PeriodicalId":520097,"journal":{"name":"The Journal of Clinical Investigation","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142440505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune-related events in individuals with solid tumors on immunotherapy associate with Th17 and Th2 signatures","authors":"Chester J. Kao, Soren Charmsaz, Stephanie L. Alden, Madelena Brancati, Howard L. Li, Aanika Balaji, Kabeer Munjal, Kathryn Howe, Sarah Mitchell, James Leatherman, Ervin Griffin, Mari Nakazawa, Hua-Ling Tsai, Ludmila Danilova, Chris Thoburn, Jennifer Gizzi, Nicole E. Gross, Alexei Hernandez, Erin M. Coyne, Sarah M. Shin, Jayalaxmi Suresh Babu, George W. Apostol, Jennifer Durham, Brian J. Christmas, Maximilian F. Konig, Evan J. Lipson, Jarushka Naidoo, Laura C. Cappelli, Aliyah Pabani, Yasser Ged, Marina Baretti, Julie Brahmer, Jean Hoffman-Censits, Tanguy Y. Seiwert, Rachel Garonce-Hediger, Aditi Guha, Sanjay Bansal, Laura Tang, Elizabeth M. Jaffee, G. Scott Chandler, Rajat Mohindra, Won Jin Ho, Mark Yarchoan","doi":"10.1172/jci176567","DOIUrl":"https://doi.org/10.1172/jci176567","url":null,"abstract":"<b>BACKGROUND. </b>Immune-related adverse events (irAEs) and their associated morbidity/mortality are a key concern for patients receiving immune checkpoint inhibitors (ICIs). Prospective evaluation of the drivers of irAEs in a diverse pan-tumor cohort is needed to identify patients at greatest risk and to develop rational treatment and interception strategies.","PeriodicalId":520097,"journal":{"name":"The Journal of Clinical Investigation","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142440388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}