Induction of Th1 and Th2 CD4⁺ T cell responses by oral or parenteral immunization with ISCOMS

Abstract

We examined the ability of oral or parenteral immunization with immune stimulating complexes containing ovalbumin (ISCOMS-OVA) to prime T cell proliferative and cytokine responses. A single subcutaneous immunization with ISCOMS-OVA primed potent antigen-specific proliferative responses in the draining popliteal lymph node, which were entirely dependent on the presence of CD4+ T cells. CD8+ T cells did not proliferate in vitro even in the presence of the appropriate peptide epitope and exogenous interleukin (IL)-2. Primed popliteal lymph node cells produced IL-2, IL-5 and interferon (IFN)-gamma, but not IL-4 when restimulated with OVA in vitro. Serum antigen-specific IgG1 and IgG2a antibody responses were also primed by subcutaneous immunization with ISCOMS-OVA, confirming the stimulation of both Th1 and Th2 cells in vivo. Spleen cells from subcutaneously primed mice produced a similar pattern of cytokines, indicating that disseminated priming had occurred. Oral immunization with ISCOMS-OVA also primed local antigen-specific proliferative responses in the mesenteric lymph node and primed an identical pattern of systemic cytokine responses in the spleen. The ability of ISCOMS to prime both Th1 and Th2 CD4+ T cell responses may be central to their potent adjuvant activities and confirm the potential of ISCOMS as future oral vaccine vectors.

Immunological properties of recombinant classical swine fever virus NS3 protein in vitro and in vivo

“…Nevertheless, it can be concluded that a likely scenario is that translation of the in vitro antigenic potential of NS3 to the in vivo situation requires an appropriate delivery of the NS3 to antigen presenting cells (APC) enabling cross-presentation to CD8 + T cells. One potential alternative formulation concept which should mediate cross-presentation is the use of delivery vehicles such as virus-like particles (VLP) [3], immune complexes [26], ISCOMS [19,32] or bacterial toxin-delivery into the APC cytoplasm [6,9,18]. Alternatively, DNA vaccination approaches could possibly be improved by addition of the NS3 gene.…”

CTA1-DD-Immune Stimulating Complexes: a Novel, Rationally Designed Combined Mucosal Vaccine Adjuvant Effective with Nanogram Doses of Antigen

“…Mice were bled for primary serum Ab responses at this time and also 7 days after DTH challenge to assess secondary responses. Anti-OVA total IgG, IgG1, and IgG2a isotype responses were measured by ELISA, as described previously (21).…”

ISCOMs: an adjuvant with multiple functions

“…Production of IL-2 was first observed in a study by Fossum et al [86] and has been demonstrated after immunization with several antigens in ISCOMs, including influenza antigen [77,80,82,86,87], OVA [88,89], HSV type 1 glycoproteins [90], and EBV gp340 [91]. Immunization with ISCOMs containing these antigens [77,80,82,[87][88][89][90][91], or antigens from the parasites L. major [28,92,93] [76].…”