Nasal and subcutaneous administration of recombinant vaccine loaded in PLGA nanoparticles: Cytokine responses against HTLV-۱

Human T-cell leukemia/Lymphoma virus type ۱ (HTLV-۱) is estimated to infect approximately ۲۵ million people worldwide. The major HTLV-۱ diseases are adult T-cell leukemia (ATL) and tropical spastic paraparesis (TSP/HAM), as well as other chronic inflammatory diseases [۱]. The HTLV-۱ genome of ۹۰۳۲ nucleotides contains the gag, pol, env genes, and pX region, that pX encodes Tax and Rex proteins, which are crucial for viral replication, and regulation of mRNA splicing, respectively. Indeed, the structural proteins of HTLV-۱ are encoded by gag and env genes. Gag proteins are sufficient to assemble and release virus particles, while pol proteins are required for transcription and protease functions. Additionally, envelope glycoproteins comprising gp۲۱ and gp۴۶ subunits are exposed at the HTLV-۱ surface and infected host cells to access the immune system of the host during the infectious process and stimulate systemic immune responses in HTLV-۱ infected individuals. The stability of the HTLV-۱ genome provides a promising approach to design and construct an effective vaccine against HTLV-۱ [۲,۳]. The biodegradable, biocompatible, and non-toxic PLGA NPs have been approved by the FDA as the controlled release delivery system [۴]. The potent adjuvant effect of PLGA nanospheres was confirmed by various studies using a model antigen such as tetanus toxoid or diphtheria, which is associated with their ability to be effectively taken up by APCs. The small size and large surface area of polymeric particles are significant factors in determining the rate of antigen release and the type of immunity. According to previous investigations, the PLGA NPs with a size of about ۲۰۰ nm, are optimal to interact with DCs and induce a strong cellular immune response [۵,۶]. In the present study, the immunogenicity of HTLV-۱ fusion epitope-loaded PLGA nanoparticles (NPs) was assessed in a mice model using subcutaneous (SC) or nasal inoculation.

کلیدواژه ها:

Recombinant vaccine ، PLGA ، Cellular response ، Cytokine assay ، HTLV-۱.