{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:31:28Z","timestamp":1790800288514,"version":"4.1.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T00:00:00Z","timestamp":1637020800000},"content-version":"vor","delay-in-days":1918,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,10,7]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>The assessment of Toll-like receptor (TLR) agonists as candidate adjuvants for induction of effective T helper type 1 (Th1) immunity continues to rely on the use of mice. However, the genetic variation among inbred mice may influence the efficacy of adjuvants and bias a study's conclusions. Here, we evaluated the differences in cellular and humoral responses of genetically non-identical mouse strains immunized with ovalbumin (OVA) plus alum, TLR-3, TLR-4, TLR-7\/8 or TLR-9 agonists. We found that all the tested TLR agonists recruited dendritic cells (DCs) and natural killer (NK) cells significantly into the lymph nodes, promoted DC\u2013NK cross-talk and enhanced the cellular responses in B6 strain. In contrast, TLR-3 and TLR-7\/8 were the only two agonists that showed the cellular adjuvanticity in the BALB\/c strain. Compared with other TLR agonists, TLR-3 and TLR-7\/8 were demonstrated to be the most effective adjuvants to generate interferon (IFN)-\u03b3-producing effector NK, CD4, and CD8 T cells in B6 and BALB\/c strains, respectively. We also found that compared with alum, all adjuvants induced the recruitment of B cells and production of OVA-specific immunoglobulin (Ig)G2a more effectively in both strains. In addition, the B6 strain recruited more B cells, but surprisingly produced significantly lower amounts of OVA-specific IgG2a in response to all adjuvants. However, consistent with the frequency of IFN-\u03b3-producing effector cells observed in individual strains following immunizations, we detected more OVA-specific IgG2a in serum of B6 and BALB\/c strains in response to TLR-3 and TLR-7\/8, respectively. Our data suggest that genetic background should be taken into consideration when evaluating the activities of TLR agonists for the development of prophylactic and therapeutic vaccines.<\/jats:p>","DOI":"10.1111\/cei.12841","type":"journal-article","created":{"date-parts":[[2016,7,9]],"date-time":"2016-07-09T04:23:14Z","timestamp":1468038194000},"page":"190-204","source":"Crossref","is-referenced-by-count":31,"title":["The genetic background influences the cellular and humoral immune responses to vaccines"],"prefix":"10.1093","volume":"186","author":[{"given":"M","family":"Zeng","sequence":"first","affiliation":[{"name":"Charles E. Schmidt College of Medicine, Integrated Medical Science Department, Florida Atlantic University, Boca Raton, FL, USA"},{"name":"Department of Gastrointestinal Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Nourishirazi","sequence":"additional","affiliation":[{"name":"Charles E. Schmidt College of Medicine, Integrated Medical Science Department, Florida Atlantic University, Boca Raton, FL, USA"},{"name":"Leonard M. Miller School of Medicine, The University of Miami, Miami, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Guinet","sequence":"additional","affiliation":[{"name":"Charles E. Schmidt College of Medicine, Integrated Medical Science Department, Florida Atlantic University, Boca Raton, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8813-0667","authenticated-orcid":false,"given":"M","family":"Nouri-Shirazi","sequence":"additional","affiliation":[{"name":"Charles E. Schmidt College of Medicine, Integrated Medical Science Department, Florida Atlantic University, Boca Raton, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,8,16]]},"reference":[{"key":"2021120808024776300_cei12841-bib-0001","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.drudis.2009.02.009","article-title":"The path to a successful vaccine adjuvant \u2013 \u2018the long and winding road","volume":"14","author":"O'Hagan","year":"2009","journal-title":"Drug Discov Today"},{"key":"2021120808024776300_cei12841-bib-0002","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1586\/14760584.2013.811208","article-title":"The use of Toll-like receptor 7\/8 agonists as vaccine adjuvants","volume":"12","author":"Vasilakos","year":"2013","journal-title":"Expert Rev Vaccines"},{"key":"2021120808024776300_cei12841-bib-0003","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/90609","article-title":"Toll-like receptors: critical proteins linking innate and acquired immunity","volume":"2","author":"Akira","year":"2001","journal-title":"Nat Immunol"},{"key":"2021120808024776300_cei12841-bib-0004","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.immuni.2010.10.002","article-title":"Vaccine adjuvants: putting innate immunity to work","volume":"33","author":"Coffman","journal-title":"Immunity"},{"key":"2021120808024776300_cei12841-bib-0005","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.it.2005.11.005","article-title":"Triggering TLR signaling in vaccination","volume":"27","author":"van Duin","year":"2006","journal-title":"Trends Immunol"},{"key":"2021120808024776300_cei12841-bib-0006","doi-asserted-by":"crossref","first-page":"188","DOI":"10.14712\/fb2005051060188","article-title":"Toll-like receptors. 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