Enhancement of the immune response to poorly immunogenic gangliosides after incorporation into very small size proteoliposomes (VSSP). Vaccine

Finlay Institute, Ave. 27 No. 19805, La Lisa, P.O. Box 16 017, C. de La Habana, Cuba
Vaccine (Impact Factor: 3.62). 09/1999; 18(1):190-197. DOI: 10.1016/S0264-410X(99)00219-4
Source: PubMed


Certain gangliosides are tumor-associated antigens that constitute potential targets for cancer immunotherapy. A major drawback in the design of ganglioside-based cancer vaccines, however, is the poor immunogenicity of these glycolipids. Here we report the immunological and physicochemical properties of very small size proteoliposomes (VSSP) obtained by using anionic detergents to incorporate gangliosides into the outer membrane protein complex (OMPC) of N. meningitidis. VSSP of three different gangliosides, GM3, NGcGM3 and GD3, were tested. These gangliosides differ in level of expression in normal tissues and in immunogenicity in different animal species. We show that the immunization with VSSP in an oil adjuvant consistently induced both IgM and IgG anti-ganglioside antibodies. In the mouse, the anti-ganglioside IgG fraction was not restricted to the typical T-independent isotype IgG3. Unexpectedly, significant levels of the T-dependent IgG1, IgG2a and particularly IgG2b were also found. VSSP-mediated enhancement of the immunogenicity was not restricted to the relatively immunogenic ganglioside GD3, satisfactory immune responses against highly tolerated GM3 and NGcGM3 were also obtained. Similar results were achieved in chickens and monkeys. No reactogenicity was observed even when self-gangliosides were used for immunization. VSSP overcame natural tolerance to gangliosides in an adjuvant dependent fashion.

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    • "Animal experiment was approved by the CIM's Institutional Animal Care and Use Committee (CIM, Cuba). For the immunization experiment, vaccines were prepared by mixing Her1-ECD (100 g) with very small size proteoliposomes (VSSP) adjuvant, which is obtained from the combinations of the outer membrane proteins of Neisseria meningitides with GM3 ganglioside [21]. Then, the Her1-ECD/VSSP preparations were emulsified (water in oil emulsion) in Montanide ISA51 (Mont) (Seppic, France). "
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    • "2.2. CIGB-247-v CIGB-247-V is a combination of a recombinant mutated variant of human VEGF-A isoform 121, fused to the first 47 aminoacids of the Neisseria meningitidis P64K protein (Morera et al., 2008), and a bacterially-derived adjuvant formed by very small size particles (VSSP) obtained from the N. meningitidis outer membrane (Estevez et al., 1999 "
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    • "Moreover, some adjuvants are able to reduce the inhibitory function of tumor-induced MDSCs [23-25]. Among these, we have previously reported the VSSP, which is a nanoparticulated adjuvant obtained by the combination of outer membrane vesicles from Neisseria meningitidis (containing TLR2 and TLR4 agonists) and GM3 ganglioside [26]. This adjuvant induces DCs maturation and antigen cross-presentation to CD8+ T cells in tumor-free mice [27,28]. "
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