The iscom structure as an immune-enhancing moiety: experience with viral systems

Claassen, Ivo; Osterhaus, Albert D. M. E.

doi:10.1016/0923-2494(92)80065-s

Cited by 66 publications

(25 citation statements)

References 51 publications

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“…Although both ISCOMs and Iscom Matrix are immunostimulatory, there may be some advantages in incorporating molecules in ISCOMs, either naturally (through an intact transmembrane domain) or by chemically or physically altering the protein structure to obtain insertion or association [3,[10][11][12]. Possible advantages of associating proteins with ISCOMs include partial purification or enrichment of membrane-bound molecules, correct presentation of proteins for immune recognition, increased uptake of protein [3,[10][11][12][13], and enhanced induction of CTL [14].…”

Section: The Iscom Particlementioning

confidence: 99%

“…Possible advantages of associating proteins with ISCOMs include partial purification or enrichment of membrane-bound molecules, correct presentation of proteins for immune recognition, increased uptake of protein [3,[10][11][12][13], and enhanced induction of CTL [14].…”

Section: The Iscom Particlementioning

confidence: 99%

“…ISCOMs have been made with amphipathic molecules derived from many sources including cell wall and membrane proteins from viruses such as Herpes Simplex type 1 (HSV-1), cytomegalovirus (CMV), Epstein Barr virus (EBV), hepatitis B, rabies, and influenza; bacteria such as Neisseria gonorrhoeae, Escherichia coli, and Brucella abortus and parasites such as Toxoplasma gondii, Plasmodium falciparum, and Leishmania major [2,3,7,13,27,28]. Antigens that are derived from purified organisms or cell membranes and have the ability to incorporate into ISCOMs are generally proteins, glycoproteins, or lipoproteins that are normally anchored into the cell or viral membrane by a hydrophobic transmembrane sequence or by lipid [3,12,13,[28][29][30].…”

Section: Protein Association With Iscoms and Iscom Matrixmentioning

confidence: 99%

“…Antigens that are derived from purified organisms or cell membranes and have the ability to incorporate into ISCOMs are generally proteins, glycoproteins, or lipoproteins that are normally anchored into the cell or viral membrane by a hydrophobic transmembrane sequence or by lipid [3,12,13,[28][29][30]. When ISCOMs are made, these molecules are extracted by detergent treatment and integrate into the lipid-saponin matrix when the detergent is removed and ISCOM particles form [13,16].…”

Section: Protein Association With Iscoms and Iscom Matrixmentioning

confidence: 99%

“…These characteristics gave ISCOMs their ability to induce strong immune responses to a variety of antigens in a number of species. ISCOMs, unlike many other vaccine adjuvants, appear to promote a broad immune response by simultaneously promoting high levels of antibody and strong T cell responses, including enhanced cytokine secretion and activation of cytotoxic T lymphocyte (CTL) responses [2,3]. The ability to stimulate CTL may be important in generating effective immune responses to virusinfected cells and possibly cancerous cells.…”

Section: Introductionmentioning

confidence: 99%

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ISCOMs: an adjuvant with multiple functions

Sjölander

Cox

Barr

1998

Journal of Leukocyte Biology

158

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Section: The Iscom Particlementioning

confidence: 99%

Section: The Iscom Particlementioning

confidence: 99%

Section: Protein Association With Iscoms and Iscom Matrixmentioning

confidence: 99%

Section: Protein Association With Iscoms and Iscom Matrixmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

ISCOMs: an adjuvant with multiple functions

Sjölander

Cox

Barr

1998

Journal of Leukocyte Biology

158

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Antigen detection in vivo after immunization with different presentation forms of rabies virus antigen: involvement of marginal metallophilic macrophages in the uptake of immune‐stimulating complexes

1995

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Several mechanisms have been postulated to explain the relatively high immunogenicity of antigens presented in immune-stimulating complexes (iscom). Their potency can in part be explained by the specific targeting of these structures to cells presenting antigens to the immune system. However, until now no method for the subcellular detection of iscom in situ was available. In the present study, a novel, fast and simple method for the detection of iscoms in situ is demonstrated. By making use of the lipophilic fluorescent carbocyanine dyes, 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) and 3,3'-dioctadecyloxacarbocyanine perchlorate (DiO), rabies virus antigen and iscom prepared with this antigen were visualized with fluorescence microscopy. The labeled antigen and iscoms were observed in macrophages of spleen and liver of mice within 1-2 h after intravenous administration. When administered intramuscularly or in the footpad, uptake in macrophages of draining lymph nodes could be demonstrated. In the spleen, labeled inactivated virus antigen localized preferentially in the marginal zone macrophages and to a lesser extent in the red pulp macrophages. In contrast, antigen presented in iscom was taken up mainly by the marginal metallophilic macrophages and to a much lesser extend by marginal zone macrophages or follicular-dendritic and -B cells. This method enables the detection of iscom and membrane viruses and allows the analysis of their relation to antigen-presenting cells in situ. Here, we demonstrate that iscom containing rabies virus antigen are taken up by a subset of macrophages in the spleen distinct from those that take up inactivated rabies virus antigen not presented in iscom, thereby possibly explaining the observed difference in immunogenicity of these antigen preparations. Furthermore, we show a lower efficiency on the induction of humoral and cellular responses after intravenous immunization for both types of antigen when compared with subcutaneous immunization.

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

1995

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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.

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The iscom structure as an immune-enhancing moiety: experience with viral systems

Cited by 66 publications

References 51 publications

ISCOMs: an adjuvant with multiple functions

ISCOMs: an adjuvant with multiple functions

Antigen detection in vivo after immunization with different presentation forms of rabies virus antigen: involvement of marginal metallophilic macrophages in the uptake of immune‐stimulating complexes

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

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The iscom structure as an immune-enhancing moiety: experience with viral systems

Cited by 66 publications

References 51 publications

ISCOMs: an adjuvant with multiple functions

ISCOMs: an adjuvant with multiple functions

Antigen detection in vivo after immunization with different presentation forms of rabies virus antigen: involvement of marginal metallophilic macrophages in the uptake of immune‐stimulating complexes

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

Contact Info

Product

Resources

About

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