期刊
VACCINES
卷 9, 期 7, 页码 -出版社
MDPI
DOI: 10.3390/vaccines9070782
关键词
malaria; recombinant vaccine; fusion chimera; dipeptide; hydrogel; immunogenicity
资金
- Department of Biotechnology, New Delhi, India [BT/PR31130/MED/15/197/2019]
A fusion chimeric vaccine composed of multiple protective domains was developed to enhance immune responses and reduce morbidity caused by Plasmodium falciparum. The tag-free recombinant PfMSPFu24 was successfully expressed and purified, and shown to be highly immunogenic with a human-compatible adjuvant. Additionally, two dipeptides based hydrogels were investigated as effective delivery platforms for the antigen, showing promising results in stimulating specific antibody titers and invasion inhibitory activity.
A fusion chimeric vaccine comprising multiple protective domains of different blood-stage Plasmodium falciparum antigens is perhaps necessary for widening the protective immune responses and reducing the morbidity caused by the disease. Here we continue to build upon the prior work of developing a recombinant fusion chimera protein, His-tagged PfMSP-Fu24, by producing it as a tag-free recombinant protein. In this study, tag-free recombinant PfMSPFu24 (rFu24) was expressed in Escherichia coli, and the soluble protein was purified using a three-step purification involving ammonium sulphate precipitation followed by 2-step ion exchange chromatography procedures and shown that it was highly immunogenic with the human-compatible adjuvant Alhydrogel. We further investigated two dipeptides, phenylalanine-alpha, beta-dehydrophenylalanine (F Delta F) and Leucine-alpha, beta-dehydrophenylalanine (L Delta F) based hydrogels as effective delivery platforms for rFu24. These dipeptides self-assembled spontaneously to form a highly stable hydrogel under physiological conditions. rFu24 was efficiently entrapped in both the F increment F and L increment F hydrogels, and the three-dimensional (3D) mesh-like structures of the hydrogels remained intact after the entrapment of the antigen. The two hydrogels significantly stimulated rFu24-specific antibody titers, and the sera from the immunized mice showed an invasion inhibitory activity comparable to that of Alhydrogel. Easily synthesized dipeptide hydrogels can be used as an effective antigen delivery platform to induce immune responses.
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