The attenuated or non-pathogenic live vectors have been evolved specifically to deliver DNA into cells as efficient delivery tools in gene therapy. Recently, a non-pathogenic protozoan, Leishmania tarentolae (L.tar) has attracted a great attention. In current study, we used Leishmania expression system (LEXSY) for stable expression of HPV16 E7 linked to different mini-chaperones [N-/C-terminal of gp96] and compared their immunogenicity and protective effects in C57BL/6 mice against TC-1 challenge. TC-1 murine model is primary C57BL/6 mice lung epithelial cells co-transformed with HPV16 E6, HPV16 E7 and ras oncogenes. Our results showed that subcutaneous administration of mice with both the recombinant L.tar-E7-NT

The development of an efficient vaccine against high-risk HPV types can reduce the incidence rates of cervical cancer by generating anti-tumor protective responses. Traditionally, the majority of prophylactic viral vaccines are composed of live, attenuated or inactivated viruses. Among them, the design of an effective and low-cost vaccine is critical. Inactivated vaccines especially heat-killed yeast cells have emerged as a promising approach for generating antigen-specific immunotherapy. Recent studies have indicated that yeast cell wall components possess adjuvant activities. Moreover, a non-pathogenic protozoan, Leishmania tarentolae (L.tar) has attracted a great attention as a live candidate vaccine. In current study, immunological and protective efficacy of whole recombinant killed Pichia pastoris and Leishmania tarentolae expressing HPV16 L1 capsid protein was evaluated in tumor mice model. We found that Pichia-L1, L.tar-L1 and Gardasil groups increase the IgG2a/IgG1 ratio, indicating a relative preference for the induction of Th1 immune responses. Furthermore, subcutaneous injection of killed Pichia-L1 generated the significant L1-specific IFN-γ immune response as well as the best protective effects in vaccinated mice as compared to killed L.tar-L1, killed Pichia pastoris, killed L.tar and PBS groups. Indeed, whole recombinant Leishmania tarentolae could not protect mice against C3 tumor mice model. These data suggest that Pichia-L1 may be a candidate for the control of HPV infections.

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<p class="a">Successful vaccine development requires knowing which adjuvants to use and how to formulate adjuvants and antigens to achieve stable, safe and immunogenic vaccines. There is growing literature on immuno-regulatory and adjuvant functions of heat shock proteins (HSPs) in the development of preventive and therapeutic vaccines against cancer and infectious diseases. These extremely conserved molecules associate with antigenic peptides from tumor, virus and intracellular bacteria, present these loaded antigens to both MHC class I and class II molecules and activate specific T cells. This review aims to summarize the data on the HSP roles as the efficient tools in cancer. The ability of heat shock proteins to chaperone peptides (e.g., antigenic peptides); interact with antigen presenting cells (APCs) through a receptor; stimulate APCs to secrete inflammatory cytokines; and mediate maturation of dendritic cells, permit the utilization of these proteins to develop a new generation of prophylactic and therapeutic vaccines against cancers and infectious diseases. Furthermore, some cancers demonstrate elevated levels of HSPs and their expression has been associated with cell proliferation and disease prognosis. New adjuvant development is needed to identify novel combinations of adjuvants and formulations capable of inducing strong, long lasting humoral and cellular immune responses in humans. Numerous challenges remain related to adjuvant development. Among efficient adjuvants, it has been shown that heat shock proteins induce cross-presentation of antigens by dendritic cells (DC) as well as DC maturation. These properties make HSP-antigen complexes good candidates to prime CD8+ T cell responses against tumor-associated antigens. Moreover, these conserved proteins can be used as diagnostic biomarkers in various cancers.</p>

One approach to improve the vaccine quality is the incorporation of immunomodulators and/or adjuvants with modified delivery systems. The use of delivery systems especially chemical carriers is a promising strategy in the prevention and treatment of infections, cancers, allergies and autoimmune diseases. These systems are able to elicit an effective immune response as well as stability and safety in vaccine development. Synthetic microparticles, liposomes, chitosan, virus like particle, polymeric nanogel, phytosome, noisome, and micro/ nanospheres have been applied as carriers, providing a broad variety of immunomodulatory effects in vaccines. The potency and nature of immune responses rely on the physicochemical properties of the vaccine constructs (e.g., size and charge), the route of injection, the biochemical characteristics and the amount of antigen. Three main steps are necessary for vaccine efficiency such as targeting, activation and transfection/ antigen presentation. These systems can generally influence the type and direction of immune responses. This review describes different vaccine delivery systems developed to generate immunomodulatory effects.