{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,11,10]],"date-time":"2024-11-10T05:01:58Z","timestamp":1731214918848,"version":"3.28.0"},"reference-count":24,"publisher":"Oceanside Publications Inc.","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["allergy asthma proc"],"published-print":{"date-parts":[[2024,11,1]]},"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Adverse allergic reactions due to the administration of vaccines developed for the protection of coronavirus disease 2019 (COVID-19) have been reported since the initiation of the vaccination campaigns in December 15, 2020. Current analyses provided by the Centers\n for Disease Control and Prevention and the U.S. Food and Drug Administration in the United States have estimated the rates of anaphylactic reactions in 2.5 and 11.1 per million of messenger RNA (mRNA) 1273 and BNT162b2 vaccines administered, respectively. The mechanisms by which these mRNA\n vaccines induce adverse vaccine reactions have been the subject of conflicting reports. Although skin testing with excipient components found in mRNA-1273 and BNT162b2 vaccines, such as polyethylene glycol (PEG) and related vaccine lipid products, were originally recommended to identify potential\n predictive biomarkers of adverse allergic reactions, more recent evidence has suggested that routine skin testing with these vaccine excipients have poor predictability and do not correlate with susceptibility to vaccine injury.  <jats:bold>Objective:<\/jats:bold> The goal of this proof-of-concept\n (POC) exploratory study was to investigate the role of leukocyte activation (LA) induced by lipid excipients found in mRNA COVID-19 vaccines in the pathogenesis of COVID-19 mRNA vaccine\u2010associated adverse reactions by using an LA assay developed in our laboratory.  <jats:bold>Results:<\/jats:bold>\n An LA assay was performed on blood samples obtained from 30 study subjects who were assigned to three study groups: group 1 consisted of 10 subjects who had received an mRNA COVID-19 vaccine and developed a serious vaccine adverse reaction; group 2 consisted of 10 subjects who had received\n a COVID-19 vaccine and developed a mild adverse reaction; and group 3 consisted of 10 subjects who had not received a COVID-19 vaccine and were asymptomatic. Five excipients were tested in each of the 10 subjects; hence, a potential of 50 reactions could be expressed in each of the three groups.\n In the subjects in group 1 who had shown clinically severe vaccine effects, 8 of 50 (16%) had severe LA index (LAI) responses (&gt;144.83), 12 of 50 (24%) had moderate LAI responses (87.62 \u2010144.82), and 30 of 50 (60%) had no reaction (0 \u2010 87.61). In the subjects in group 2 who\n had shown clinically mild vaccine effects, 4 of 50 (8%) had severe LAI responses (&gt;144.83), 9 of 50 (18%) had moderate LAI responses (87.62 \u2010144.82), and 37 of 50 (74%) had no reaction. In the subjects in group 3 who had not received the vaccine and, therefore, had no clinical vaccine\n effects, 2 of 50 (4%) had severe LAI responses (&gt;144.83), 10 of 50 (20%) had moderate LAI responses (87.62 \u2010144.82), and 38 of 50 (76%) had no reaction LA index (LAI) responses.  <jats:bold>Conclusion:<\/jats:bold> The results of this exploratory POC study suggest that the measurement\n of LA induced by PEG and other vaccine-related lipid excipients found in mRNA COVID-19 vaccines may provide a novel and useful predictive biomarker associated with adverse non\u2010immunoglobulin E (IgE) related allergic reactions to these vaccines. The study results also underscore growing\n concerns related to these non-IgE hypersensitivity reactions and their potential for pathogenesis of adverse vaccine reactions. This is particularly noteworthy because, with the continuing emergence of novel and evolving variants of severe acute respiratory syndrome corona-virus 2 mutants,\n yearly immunization with mRNA vaccines will most likely be recommended. Although the study was not sufficiently powered to draw definitive conclusions with regard to associations between vaccine-associated COVID-19 reactions and LA, the trends of a more severe set of clinical reactions seen\n associated with LAI reactivity scores, particularly with ALC-0159 (2-[{polyethylene glycol} 2000]-N,N-ditetradecylacetamide), suggest a potential benefit worthy of exploration in future randomized controlled trials.<\/jats:p>","DOI":"10.2500\/aap.2024.45.240040","type":"journal-article","created":{"date-parts":[[2024,11,9]],"date-time":"2024-11-09T04:32:18Z","timestamp":1731126738000},"page":"438-446","source":"Crossref","is-referenced-by-count":1,"title":["The role of leukocyte activation in suspected Non-IgE excipient-related COVID-19 vaccine reactions: An exploratory hypothesis-driven study of pathogenesis"],"prefix":"10.2500","volume":"45","author":[{"given":"Yen-Chih","family":"Huang","sequence":"first","affiliation":[{"name":"From the Cell Science Systems Corporation, Deerfield Beach, Florida;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Caldarone","sequence":"additional","affiliation":[{"name":"From the Cell Science Systems Corporation, Deerfield Beach, Florida;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cherrie","family":"Sherman","sequence":"additional","affiliation":[{"name":"From the Cell Science Systems Corporation, Deerfield Beach, Florida;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roger","family":"Deutsch","sequence":"additional","affiliation":[{"name":"From the Cell Science Systems Corporation, Deerfield Beach, Florida;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaeil","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Bioinformatics and Biomathematics, Georgetown University Medical Center, Washington, D.C.;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph A.","family":"Bellanti","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Georgetown University School of Medicine, Washington, D.C.;"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1355","reference":[{"key":"B1","first-page":"601","article-title":"Pfizer-BioNTech (BNT162b2), Moderna (mRNA-1273) COVID-19 mRNA vaccines and hypersensitivity reactions","volume":"114","author":"Haq","year":"2022","journal-title":"J Natl Med Assoc"},{"key":"B2","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.alit.2021.04.003","article-title":"Allergy to COVID-19 vaccines: a current update","volume":"70","author":"Cabanillas","year":"2021","journal-title":"Allergol Int"},{"key":"B3","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1007\/s12026-023-09357-5","article-title":"COVID-19 vaccines adverse events: potential molecular mechanisms","volume":"71","author":"Lamprinou","year":"2023","journal-title":"Immunol Res"},{"key":"B4","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1080\/07853890.2022.2031274","article-title":"Emerging COVID-19 variants and their impact on SARS-CoV-2 diagnosis, therapeutics and vaccines","volume":"54","author":"Fernandes","year":"2022","journal-title":"Ann Med"},{"key":"B5","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1016\/j.jaip.2020.12.047","article-title":"mRNA vaccines to prevent COVID-19 disease and reported allergic reactions: current evidence and suggested approach","volume":"9","author":"Banerji","year":"2021","journal-title":"J Allergy Clin Immunol Pract"},{"key":"B6","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1016\/j.jaip.2021.01.022","article-title":"The COVID-19 pandemic in 2021: avoiding overdiagnosis of anaphylaxis risk while safely vaccinating the world","volume":"9","author":"Greenhawt","year":"2021","journal-title":"J Allergy Clin Immunol Pract"},{"key":"B7","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.anai.2021.01.017","article-title":"Insights from American College of Allergy, Asthma, and Immunology COVID-19 Vaccine Task Force: allergic reactions to mRNA SARS-CoV-2 vaccines","volume":"126","author":"Murphy","year":"2021","journal-title":"Ann Allergy Asthma Immunol"},{"key":"B8","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1016\/j.jaci.2021.04.002","article-title":"Potential mechanisms of anaphylaxis to COVID-19 mRNA vaccines","volume":"147","author":"Risma","year":"2021","journal-title":"J Allergy Clin Immunol"},{"key":"B9","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1021\/acs.bioconjchem.3c00174","article-title":"PEGylated lipid nanoparticle formulations: immunological safety and efficiency perspective","volume":"34","author":"Tenchov","year":"2023","journal-title":"Bioconjug Chem"},{"key":"B10","doi-asserted-by":"crossref","first-page":"2667","DOI":"10.1016\/j.jaip.2022.07.027","article-title":"Incidence and risk factors of immediate hypersensitivity reactions and immunization stress-related responses with COVID-19 mRNA vaccine","volume":"10","author":"Imai","year":"2022","journal-title":"J Allergy Clin Immunol Pract"},{"key":"B11","doi-asserted-by":"crossref","first-page":"4693","DOI":"10.1016\/j.vaccine.2023.06.039","article-title":"Hypersensitivity reactions to anti-SARS-CoV-2 vaccines: basophil reactivity to excipients","volume":"41","author":"Pignatti","year":"2023","journal-title":"Vaccine"},{"key":"B12","doi-asserted-by":"crossref","first-page":"2924","DOI":"10.1111\/all.15278","article-title":"Do basophil activation tests help elucidate allergic reactions to the ingredients in COVID-19 vaccines?","volume":"77","author":"Eberlein","year":"2022","journal-title":"Allergy"},{"key":"B13","doi-asserted-by":"crossref","first-page":"2067","DOI":"10.1111\/all.15148","article-title":"The value of the basophil activation test in the evaluation of patients reporting allergic reactions to the BNT162b2 mRNA COVID-19 vaccine","volume":"77","author":"Labella","year":"2022","journal-title":"Allergy"},{"key":"B14","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.anai.2022.03.006","article-title":"Coronavirus disease 2019 vaccine administration in patients with reported reactions to polyethylene glycol- and polysorbate-containing therapeutics","volume":"129","author":"Otani","year":"2022","journal-title":"Ann Allergy Asthma Immunol"},{"key":"B15","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1111\/cea.14143","article-title":"COVID-19 vaccines and anaphylaxis\u2014evaluation with skin prick testing, basophil activation test and immunoglobulin E","volume":"52","author":"Csuth","year":"2022","journal-title":"Clin Exp Allergy"},{"key":"B16","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.jaci.2021.04.032","article-title":"Basophil reactivity to BNT162b2 is mediated by PEGylated lipid nanoparticles in patients with PEG allergy","volume":"148","author":"Troelnikov","year":"2021","journal-title":"J Allergy Clin Immunol"},{"key":"B17","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1093\/cid\/ciab437","article-title":"Increased peripheral blood neutrophil activation phenotypes and neutrophil extracellular trap formation in critically ill coronavirus disease 2019 (COVID-19) patients: a case series and review of the literature","volume":"74","author":"Masso-Silva","year":"2022","journal-title":"Clin Infect Dis"},{"key":"B18","doi-asserted-by":"crossref","first-page":"e59","DOI":"10.2500\/aap.2021.42.210021","article-title":"Studies of mitochondrial and nuclear DNA released from food allergen-activated neutrophils. Implications for non-IgE food allergy","volume":"42","author":"K\u00f6nig","year":"2021","journal-title":"Allergy Asthma Proc"},{"key":"B19","first-page":"325","article-title":"Morphologic alterations of blood cells in the impedance aggregometer","volume":"11","author":"Lehmann","year":"1985","journal-title":"Blood Cells"},{"key":"B20","doi-asserted-by":"crossref","first-page":"e000164","DOI":"10.1136\/bmjgast-2017-000164","article-title":"Efficacy of individualised diets in patients with irritable bowel syndrome: a randomised controlled trial","volume":"4","author":"Ali","year":"2017","journal-title":"BMJ Open Gastroenterol"},{"key":"B21","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s12986-018-0260-4","article-title":"A leukocyte activation test identifies food items which induce release of DNA by innate immune peripheral blood leucocytes","volume":"15","author":"Garcia-Martinez","year":"2018","journal-title":"Nutr Metab (Lond)"},{"key":"B22","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1111\/all.15187","article-title":"The form of PEG matters: PEG conjugated with lipids and not PEG alone could be the specific form involved in allergic reactions to COVID-19 vaccines","volume":"77","author":"Cabanillas","year":"2022","journal-title":"Allergy"},{"key":"B23","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/s13142-017-0500-6","article-title":"Why null results do not mean no results: negative findings have implications for policy, practice, and research","volume":"7","author":"Miller-Halegoua","year":"2017","journal-title":"Transl Behav Med"},{"key":"B24","doi-asserted-by":"crossref","first-page":"e12077","DOI":"10.2196\/12077","article-title":"The internet of things in health care in Oxford: protocol for proof-of-concept projects","volume":"7","author":"Meinert","year":"2018","journal-title":"JMIR Res Protoc"}],"container-title":["Allergy and Asthma Proceedings"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ingentaconnect.com\/content\/ocean\/aap\/2024\/00000045\/00000006\/art00015","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,9]],"date-time":"2024-11-09T04:32:28Z","timestamp":1731126748000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ingentaconnect.com\/content\/10.2500\/aap.2024.45.240040"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,1]]},"references-count":24,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,11,1]]}},"alternative-id":["1088-5412(20241101)45:6L.438;1-"],"URL":"https:\/\/doi.org\/10.2500\/aap.2024.45.240040","relation":{},"ISSN":["1088-5412"],"issn-type":[{"value":"1088-5412","type":"print"}],"subject":[],"published":{"date-parts":[[2024,11,1]]}}}