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.

Alpha-galactosylceramide enhances mucosal immunity to oral whole-cell cholera vaccines

“…Furthermore, it is known that the genetic background influences the antibody and cellular immune responses to vaccines. 25 Here oral α-GalCer administration was particularly effective in enhancing intestinal and systemic anti-LPS antibody responses in BALB/c mice but did not promote detectable antigen-specific intestinal and systemic Th1 responses. Consequently, the enhancement of antigen-specific intestinal IgA responses by α-GalCer appears to be independent of antigen-specific Th1 responses.…”

Onchocerca volvulus bivalent subunit vaccine induces protective immunity in genetically diverse collaborative cross recombinant inbred intercross mice

“…All previous pre-clinical development of the Ov vaccine was based on experiments done exclusively in BALB/cByJ and C57BL/6J mice. While these studies have established the vaccine’s efficacy and its dependence on humoral and cellular immunity 20 , 23 , they are limited by the genomic homogeneity within these two inbred strains of mice 24 . The lack of genetic diversity in these animal models may become an issue when the vaccine is advanced to clinical trial in humans, when more diverse host genetics may impact vaccine efficacy 25 – 28 .…”

Activation of Human Monocytes by Colloidal Aluminum Salts

“…For example, alum is a Th2-polarizing adjuvant in mice, 53 but the extent of this effect depends on the mouse strain. 54 Moreover, in humans, a mixed Th1/ Th2-polarizing response has been observed. 1,19,55,56 Indications of the activation of monocytes that play a role in the onset of a mixed Th1/Th2 response was also found in this study by the enhanced expression of IL-4 (Th2-polarizing) and IFNg (Th1-polarizing) on incubation with gibbsite or alum.…”