{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:31:01Z","timestamp":1787016661416,"version":"build-2736575974"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2013,7,1]],"date-time":"2013-07-01T00:00:00Z","timestamp":1372636800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2013,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Interindividual variations in vaccine-induced immune responses are in part due to host genetic polymorphisms in the human leukocyte antigen (HLA) and other gene families. This study examined associations between HLA genotypes, haplotypes, and homozygosity and protective antigen (PA)-specific cellular immune responses in healthy subjects following immunization with Anthrax Vaccine Adsorbed (AVA). While limited associations were observed between individual HLA alleles or haplotypes and variable lymphocyte proliferative (LP) responses to AVA, analyses of homozygosity supported the hypothesis of a \u201cheterozygote advantage.\u201d Individuals who were homozygous for any HLA locus demonstrated significantly lower PA-specific LP than subjects who were heterozygous at all eight loci (median stimulation indices [SI], 1.84 versus 2.95,\n                    <jats:italic>P<\/jats:italic>\n                    = 0.009). Similarly, we found that class I (HLA-A) and class II (HLA-DQA1 and HLA-DQB1) homozygosity was significantly associated with an overall decrease in LP compared with heterozygosity at those three loci. Specifically, individuals who were homozygous at these loci had significantly lower PA-specific LP than subjects heterozygous for HLA-A (median SI, 1.48 versus 2.13,\n                    <jats:italic>P<\/jats:italic>\n                    = 0.005), HLA-DQA1 (median SI, 1.75 versus 2.11,\n                    <jats:italic>P<\/jats:italic>\n                    = 0.007), and HLA-DQB1 (median SI, 1.48 versus 2.13,\n                    <jats:italic>P<\/jats:italic>\n                    = 0.002) loci, respectively. Finally, homozygosity at an increasing number (\u22654) of HLA loci was significantly correlated with a reduction in LP response (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.001) in a dose-dependent manner. Additional studies are needed to reproduce these findings and determine whether HLA-heterozygous individuals generate stronger cellular immune response to other virulence factors (\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Bacillus anthracis<\/jats:named-content>\n                    LF and EF) than HLA-homozygous subjects.\n                  <\/jats:p>","DOI":"10.1128\/iai.00269-13","type":"journal-article","created":{"date-parts":[[2013,5,7]],"date-time":"2013-05-07T00:00:00Z","timestamp":1367884800000},"page":"2584-2591","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":23,"title":["Human Leukocyte Antigens and Cellular Immune Responses to Anthrax Vaccine Adsorbed"],"prefix":"10.1128","volume":"81","author":[{"given":"Inna G.","family":"Ovsyannikova","sequence":"first","affiliation":[{"name":"Mayo Clinic Vaccine Research Group, Mayo Clinic, Rochester, Minnesota, USA"},{"name":"Program in Translational Immunovirology and Biodefense, Mayo Clinic, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V. Shane","family":"Pankratz","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Vierkant","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas M.","family":"Pajewski","sequence":"additional","affiliation":[{"name":"Department of Biostatistical Sciences, Wake Forest University Health Sciences, Winston Salem, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conrad P.","family":"Quinn","sequence":"additional","affiliation":[{"name":"Centers for Disease Control and Prevention, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Kaslow","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert M.","family":"Jacobson","sequence":"additional","affiliation":[{"name":"Mayo Clinic Vaccine Research Group, Mayo Clinic, Rochester, Minnesota, USA"},{"name":"Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory A.","family":"Poland","sequence":"additional","affiliation":[{"name":"Mayo Clinic Vaccine Research Group, Mayo Clinic, Rochester, Minnesota, USA"},{"name":"Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota, USA"},{"name":"Program in Translational Immunovirology and Biodefense, Mayo Clinic, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.4.1781-1786.2000"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2009.08.006"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.9.5978-5987.2005"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2005.12.028"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2006.05.044"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.4161\/hv.3.5.4459"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2007.11.085"},{"key":"e_1_3_3_9_2","first-page":"713","volume-title":"Immunology and allergy clinics of North America: vaccines in the 21st century","author":"Grabenstein JD","year":"2003","unstructured":"GrabensteinJD. 2003. 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