Anti-microbial immunity augmented by extracellular matrix adjuvant from porcine small intestinal submucosa (52.22)

Developing a long-lasting protective vaccine against Staphylococcus aureus has been a challenge, since S. aureus has several mechanisms to evade the immune system. The issue is whether appropriate adjuvant(s) could overcome this evasion and elicit a robust immune response. Porcine small Intestinal submucosa (SIS) exhibits adjuvanticity against pathogenic antigens and bacterial toxins (Suckow, USPA 20100136050). However, there is as yet no report on the adjuvanticity of SIS against the intracellular pathogen S. aureus. Hence, this study was designed to assess SIS as an adjuvant, relative to alum, in terms of specific antibody response, T-cell infiltration, inflammasome activation and TLR involvement, in BALB/c mice against heat-killed S. aureus. Our results showed that SIS helped evoke high-titer antibody, but alum was ineffective in augmenting antibody response. Both SIS and alum up-regulated the mRNA expression of GATA-3 and FOXP3. Our inflammasome microarray analysis showed that unlike alum, SIS did not involve any inflammasome pathway (Nlrp1a/Nlrp3/IPAF). In comparison with Staph alone, alum significantly upregulated the mRNA expression of chemokines Ccl12, Ccl7 and Cxcl3 but SIS did not. Alum although is TLR-independent, influenced the up-regulation of the mRNA expression of TLRs 2,3,5,7 and 8. SIS also showed a similar effect. In summary although SIS was more effective than alum in antibody production against S. aureus, its mode of action needs to be explored further.