{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:27:37Z","timestamp":1787030857343,"version":"build-2736575974"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2019,3,1]],"date-time":"2019-03-01T00:00:00Z","timestamp":1551398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>CD4+ T cells play critical roles in defending against poxviruses, both by potentiating cellular and humoral responses and by directly killing infected cells. Despite this central role, the basis for pox-specific CD4+ T cell activation, specifically the origin of the poxvirus-derived peptides (epitopes) that activate CD4+ T cells, remains poorly understood. In addition, because the current licensed poxvirus vaccines can cause serious adverse events and even death, elucidating the requirements for MHC class II (MHC-II) processing and presentation of poxviral Ags could be of great use. To address these questions, we explored the CD4+ T cell immunogenicity of ectromelia, the causative agent of mousepox. Having identified a large panel of novel epitopes via a screen of algorithm-selected synthetic peptides, we observed that immunization of mice with inactivated poxvirus primes a virtually undetectable CD4+ T cell response, even when adjuvanted, and is unable to provide protection against disease after a secondary challenge. We postulated that an important contributor to this outcome is the poor processability of whole virions for MHC-II\u2013restricted presentation. In line with this hypothesis, we observed that whole poxvirions are very inefficiently converted into MHC-II\u2013binding peptides by the APC as compared with subviral material. Thus, stability of the virion structure is a critical consideration in the rational design of a safe alternative to the existing live smallpox vaccine.<\/jats:p>","DOI":"10.4049\/jimmunol.1801099","type":"journal-article","created":{"date-parts":[[2019,1,30]],"date-time":"2019-01-30T15:25:23Z","timestamp":1548861923000},"page":"1340-1349","source":"Crossref","is-referenced-by-count":10,"title":["Poor Antigen Processing of Poxvirus Particles Limits CD4+ T Cell Recognition and Impacts Immunogenicity of the Inactivated Vaccine"],"prefix":"10.1093","volume":"202","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4991-1601","authenticated-orcid":false,"given":"Katherine S","family":"Forsyth","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"DeHaven","sequence":"additional","affiliation":[{"name":"Department of Biology, La Salle University , Philadelphia, PA 19141"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2197-6892","authenticated-orcid":false,"given":"Mark","family":"Mendonca","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Thomas Jefferson University , Philadelphia, PA 19107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sinu","family":"Paul","sequence":"additional","affiliation":[{"name":"La Jolla Institute for Allergy and Immunology , La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7013-2250","authenticated-orcid":false,"given":"Alessandro","family":"Sette","sequence":"additional","affiliation":[{"name":"La Jolla Institute for Allergy and Immunology , La Jolla, CA 92037"},{"name":"Department of Medicine, University of California , San Diego, La Jolla, CA, 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8475-7910","authenticated-orcid":false,"given":"Laurence C","family":"Eisenlohr","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA 19104"},{"name":"Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,3,1]]},"reference":[{"key":"2025030417560898700_r1","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1038\/nm.3958","article-title":"Endogenous antigen processing drives the primary CD4+ T cell response to influenza","volume":"21","author":"Miller","year":"2015","journal-title":"Nat. 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