No abstract

Two human papillomavirus (HPV) viral oncoproteins, E6 and E7 represent ideal targets for development of a therapeutic HPV vaccine. It is important to reduce the rate of HPVassociated malignancies through improvement of vaccine modalities. In this study, we used a short amphipathic peptide carrier, Pep-1, for delivery of the full-length HPV16 E7 protein into mammalian cells and evaluated immune responses and protective effects of different formulations in C57BL/6 tumor mice model. Our results showed that the complexes of E7/ Pep-1 protein form stable nanoparticles through noncovalent binding with an average size of 120 to 250 nm. The efficient delivery of E7 protein by Pep-1 at molar ratio of 1:20 was detected in HEK-293T cell line for 1 h and 3 h posttransfection. Immunization with E7/Pep-1 nanoparticles at a ratio of 1:20 induced a higher Th1 cellular immune response with the predominant IgG2a and IFN-c levels than those induced by E7 protein in a murine tumor model. These data suggest that Pep-1 peptide would indicate promising applications for improvement of HPV therapeutic vaccines. V C 2016 IUBMB Life, 68(6): [459][460][461][462][463][464][465][466][467] 2016

Advances of in silico, ex vivo, and in vivo testing of the preclinical safety of newly developed pharmaceutical drugs before being administered in humans, is a fundamental step in drug manufacturing. Nowadays, animal testing plays an essential role in the evaluation of drug safety before progression into clinical trials. In recent years, several ex vivo tests have been developed and used in new screening processes to evaluate the toxicity of potential therapeutic molecules. This has led to a great replacement or reduction of in vivo assays. Accordingly, many pharmaceutical industries have a high demand for in vitro assays, and they are inclined to support the primary knowledge of developing novel drugs with adherence to the strategy of 3Rs (reduction, refinement, and replacement). It asserts that in vivo tests should be reduced, refined, and replaced by other preclinical techniques. Recently, using combinational chemistry and highthroughput screening (HTS) has increased the required information on a wide range of candidate molecules in terms of their absorption, distribution, metabolism, excretion, and toxicity (ADMET); which has resulted in a lot of ex vivo ADMET assessments. In this review, we have discussed the methods and tests which have the potential to replace the animal assays; and have addressed their advantages and limitations.

High-risk genotypes of human papillomavirus (HPV) are associated with genital cancers especially cervical cancer. United State Food and Drug Administration (USFDA) has recently licensed two first-generation prophylactic vaccines (i.e., Gardasil and Cervarix), for control of HPV 16 and 18 infections. Both vaccines are able to generate neutralizing antibodies against major capsid protein L1 assembled as virus-like particles (VLPs). To enhance protection against other HPV genotypes, second-generation vaccines are underway. A HPV L1-based nonavalent vaccine showed is potent and safe in prevention of precancerous lesions associated with HPV types 16/18/31/33/45/52/58, as well as anogenital warts associated with HPV types 6/11. This vaccine is in the advanced stage of phase III clinical trials. Other second-generation vaccines were based on L1-pentameric subunits and also the minor capsid protein L2 that have shown to be effective in preclinical studies. The L2 protein co-assembles with the L1 protein for VLP formation increasing virion aggregation. This mini-review describes two vaccination strategies including first-generation and second-generation vaccines against HPV infections.