title: The genetic background influences the cellular and humoral immune responses to vaccines.
abstract: 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-NK 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)-γ-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-γ-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.
authors.affiliation: Charles E. Schmidt College of Medicine, Integrated Medical Science Department, Florida Atlantic University, Boca Raton, FL, USA.|Department of Gastrointestinal Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
authors.forename: M
authors.initials: M
authors.lastname: Zeng
authors.affiliation: Charles E. Schmidt College of Medicine, Integrated Medical Science Department, Florida Atlantic University, Boca Raton, FL, USA.|Leonard M. Miller School of Medicine, The University of Miami, Miami, FL, USA.
authors.forename: E
authors.initials: E
authors.lastname: Nourishirazi
authors.affiliation: Charles E. Schmidt College of Medicine, Integrated Medical Science Department, Florida Atlantic University, Boca Raton, FL, USA.
authors.forename: E
authors.initials: E
authors.lastname: Guinet
authors.affiliation: Charles E. Schmidt College of Medicine, Integrated Medical Science Department, Florida Atlantic University, Boca Raton, FL, USA. mnourish@health.fau.edu.
authors.forename: M
authors.identifier: http://orcid.org/0000-0001-8813-0667
authors.initials: M
authors.lastname: Nouri-Shirazi
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D000941:Antigens / Q000276:immunology; D015415:Biomarkers; D002634:Chemotaxis, Leukocyte; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D056726:Genetic Association Studies; D000068617:Genetic Background; D007111:Immunity, Cellular / Q000235:genetics*; D056724:Immunity, Humoral / Q000235:genetics*; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D051193:Toll-Like Receptors / Q000819:agonists / Q000378:metabolism; D014612:Vaccines / Q000276:immunology*
chemical_list: D000906:Antibodies; D000941:Antigens; D015415:Biomarkers; D016207:Cytokines; D051193:Toll-Like Receptors; D014612:Vaccines
keywords: Toll-like receptors (TLRs); dendritic cells; natural killer cells; vaccination