The genetic background influences the cellular and humoral immune responses to vaccines.

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.