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Immunomodulatory effects of IP-10 chemokine along with PEI600-Tat delivery system in DNA vaccination against HPV infections.

Abstract : Although DNA vaccines represent an attractive approach for generating antigen-specific immunity, improvement of their potency is highly demanded. In the present study, three strategies including linkage to immunostimulatory molecules (N-terminal of gp96), co-administration of chemokines (IP-10 or RANTES) and PEI600-Tat as non-viral gene delivery system have been applied to enhance DNA vaccine efficacy against HPV infections. We found that C57BL/6 immunization with E7-NT-gp96 fusion gene led to increased level of IFN- compared to E7 alone. The fused genes showed considerable protective potency in tumor mice model. In addition, E7-NT-gp96 delivered with PEI600-Tat was more protective against E7-expressing tumors comparing with E7-NT-gp96 alone. Our results showed that co-administration of IP-10 with E7-NT-gp96 delivered by PEI600-Tat elicits significant IFN- production and consequently a strong preventive response against TC-1 tumor cells in contrast to increased tumor growth by RANTES co-delivery. Also in therapeutic experiment, our data showed that co-immunization of IP-10 at the same inoculation site of TC-1 along with E7-NT-gp96 delivery by PEI600-Tat is able to significantly suppress TC-1 tumor growth. The successful treatment by this immunization protocol was associated with the elevated levels of IFN- and IL-2 production in the lymph nodes. These data indicated that fusion of NT-gp96 to E7 in combination with IP-10 co-administration and PEI600-Tat delivery system can synergistically enhance the potency of HPV DNA vaccines. Therefore, this approach suggests a combinational therapeutic strategy against cervical and other HPV-related cancers.
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https://hal-riip.archives-ouvertes.fr/pasteur-00789216
Contributor : Sima Rafati <>
Submitted on : Sunday, February 17, 2013 - 11:14:50 AM
Last modification on : Wednesday, October 14, 2020 - 4:09:50 AM

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Elham Mohit, Azam Bolhassani, Farnaz Zahedifard, Negar Seyed, Ali Eslamifar, et al.. Immunomodulatory effects of IP-10 chemokine along with PEI600-Tat delivery system in DNA vaccination against HPV infections.. Molecular Immunology, Elsevier, 2013, 53 (1-2), pp.149-60. ⟨10.1016/j.molimm.2012.07.011⟩. ⟨pasteur-00789216⟩

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