Immune enhancement by novel vaccine adjuvants in autoimmune-prone NZB/W F1 mice: relative efficacy and safety

Abstract

BackgroundVaccines have profoundly impacted global health although concerns persist about their potential role in autoimmune or other adverse reactions. To address these concerns, vaccine components like immunogens and adjuvants require critical evaluation not only in healthy subjects but also in those genetically averse to vaccine constituents. Evaluation in autoimmune-prone animal models of adjuvants is therefore important in vaccine development. The objective here was to assess the effectiveness of experimental adjuvants: two phytol-derived immunostimulants PHIS-01 (phytanol) and PHIS-03 (phytanyl mannose), and a new commercial adjuvant from porcine small intestinal submucosa (SIS-H), relative to a standard adjuvant alum. Phytol derivatives are hydrophobic, oil-in water diterpenoids, while alum is hydrophilic, and SIS is essentially a biodegradable and collagenous protein cocktail derived from extracellular matrices.ResultsWe studied phthalate -specific and cross-reactive anti-DNA antibody responses, and parameters associated with the onset of autoimmune disorders. We determined antibody isotype and cytokine/chemokine milieu induced by the above experimental adjuvants relative to alum. Our results indicated that the phytol-derived adjuvant PHIS-01 exceeded alum in enhancing anti-phthalate antibody without much cross reactivity with ds-DNA. Relatively, SIS and PHIS-03 proved less robust, but they were also less inflammatory. Interestingly, these adjuvants facilitated isotype switching of anti-hapten, but not of anti-DNA response. The current study reaffirms our earlier reports on adjuvanticity of phytol compounds and SIS-H in non autoimmune-prone BALB/c and C57BL/6 mice. These adjuvants are as effective as alum also in autoimmune-prone NZB/WF1 mice, and they have little deleterious effects.ConclusionAlthough all adjuvants tested impacted cytokine/chemokine milieu in favor of Th1/Th2 balance, the phytol compounds fared better in reducing the onset of autoimmune syndromes. However, SIS is least inflammatory among the adjuvants evaluated.

Field safety experience with an autologous cancer vaccine in tumor-bearing cats: a retrospective study of 117 cases (2015–2020)

“…31,32 Moreover, the adjuvant (MIM-SIS) used in the ACV studied here is a non-irritating adjuvant that has a very low incidence of AEs, while also being capable of producing a robust immune response against co-administered antigens. 33,34 Based on the reported safety of autologous cancer vaccines among various species, and the properties of MIM-SIS, the low AE rate reported in this population of cats is likely representative of what could be expected with more widespread use.…”

Effects of Small Intestinal Submucosa (SIS) on the Murine Innate Immune Microenvironment Induced by Heat-Killed Staphylococcus aureus

“…In an earlier study, we have reported the efficiency of SIS in augmenting the immunogenic potential of soluble protein antigens like ovalbumin and keyhole-limpet hemocyanin [18]. We also described that SIS exhibits adjuvanticity without inducing any adverse pathologic inflammatory response even in autoimmune prone NZB/WF1 mice [19]. In this respect, SIS is better than some commercial adjuvants that often induce inflammatory tissue damage at sites of injection.…”

Phytol-derived novel isoprenoid immunostimulants

“…All adjuvant-treated groups registered high levels of anti-inflammatory cytokines TNFRII, TNFRI, TIMP-1. Interestingly, the Th1 and Th2 responses generated by different adjuvants was directed more toward phthalate as evident by induction of the IgG subclass, whereas the cross reactive anti-ds DNA response was mostly IgM with little IgG subclass switching, indicating no affinity maturation or memory induction, characteristics of T helper activity on antigen-specific B cells (Ghosh and Aachoui, 2011 ).…”