The immunogenicity of the tumor-associated antigen α-fetoprotein is enhanced by a fusion with a transmembrane domain

肿瘤相关抗原甲胎蛋白的免疫原性通过与跨膜结构域融合而增强

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作者:Lucile Tran, Jean-Paul Judor, Vanessa Gauttier, Michel Geist, Chantal Hoffman, Ronald Rooke, Georges Vassaux, Sophie Conchon

Aim

To investigate the ability of recombinant modified vaccinia virus Ankara (rMVA) vector to induce an immune response against a well-tolerated self-antigen.

Conclusions

The AFP transmembrane form is more immunogenic. Expressing a membrane-bound form in the context of an MVA vaccination could enhance the immunogenicity of a self-antigen.

Methods

rMVA vectors expressing different form of α-fetoprotein (AFP) were produced and characterized. Naïve mice were vaccinated with MVA vectors expressing the AFP antigen in either a secreted, or a membrane-bound, or an intracellular form. The immune response was monitored by an IFNΓ ELISpot assay and antibody detection.

Results

Vaccination with the membrane-associated form of AFP induced a stronger CD8(+) T-cell response compared to the ones obtained with the MVA encoding the secreted or the intracellular forms of AFP. Moreover, the vaccination with the membrane-bound AFP elicited the production of AFP-specific antibodies. Conclusions: The AFP transmembrane form is more immunogenic. Expressing a membrane-bound form in the context of an MVA vaccination could enhance the immunogenicity of a self-antigen.

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