SIGNAL SEQUENCE OF VEGETABLE PROTEIN AS ADJUVANT IN DNA VACCINES
The invention relates to a signal sequence of plant proteins as an adjuvant in DNA vaccines. In particular, a sequence able to guide the processing of an antigen through the mammalian secretion pathway and increase the efficacy of DNA vaccines for the prevention / treatment of tumors and infections in which the signal sequence is fused to the N- portion terminal of an antigen.
The latest generation of preventive vaccines contain pathogens obtained from molecular immunology and genetic engineering. For tumors, the Human Papillomavirus (HPV) is at the basis of cervical squamous cell carcinoma and oropharyngeal carcinogenesis. Current HPV cancer therapies are moderately successful and show relapse. Preventive vaccines reduce cases but, without their growth, prophylaxis does not impact. Hence the need for new DNA vaccines. The PGIPss plant signal sequence is used to drive HPV antigens in the human secretory pathway: 1) an attenuated variant of the HPV-16 E7 oncoprotein E7 (E7GGG) antigen associated with cervical cancer; 2) a portion of the capsid of HPV-16, L2 investigated as antigen for broad spectrum vaccines against HPV-related diseases; 3) an additional E7GGG and L2 form fused into a chimeric gene to produce a preventive/therapeutic vaccine. The constructs are cloned into vectors for mammalian expression of pcDNA3.1 and pVAX1 and to immunize C57BL6 mice. Immunization with DNA constructs using plant ss induces remarkable responses in all cases. The invention offers a vaccine that induces a strong antibody response against HPV type 16 antigens and for the SARS-CoV protein N.
- Possibility of producing vaccines against different pathogens using a single plasmid with a simple structure in which to insert the fusion antigenic sequence.
- Plant nucleotide sequence associated with that of the antigen in a single plasmid;
- High antibody response;
- Reproducible on an industrial scale;
- Use of even large antigens as the fusion involves a few added nucleotides;
- Safe vaccines that do not involve the production of chemo / cytokines or animal antigens.