In Silico Design and Immunological Studies of Two Novel Multiepitope DNA-Based Vaccine Candidates Against High-Risk Human Papillomaviruses

Abstract

Human papillomaviruses (HPV)-16 and 18 are the most prevalent types associated with cervical cancer. HPV L1 and L2 capsid proteins and E7 oncoprotein play crucial roles in HPV-related diseases. Hence, these proteins were proposed as target antigens for preventive and therapeutic vaccines. In this study, two multiepitope DNA-based HPV vaccine candidates were designed using in silico analysis including the immunogenic and conserved epitopes of HPV16/18 L1, L2 and E7 proteins (the L1-L2-E7 fusion DNA), and of heat shock protein 70 (HSP70) linked to the L1-L2-E7 DNA construct (the HSP70-L1-L2-E7 fusion DNA). Next, the expression of the L1-L2-E7 and HSP70-L1-L2-E7 multiepitope DNA constructs was evaluated in a mammalian cell line. Finally, immunological responses and antitumor effects of the DNA constructs were investigated in C57BL/6 mice. Our data indicated high expression rates of the designed multiepitope L1-L2-E7 DNA (~ 56.16%) and HSP70-L1-L2-E7 DNA (~ 80.45%) constructs in vitro. The linkage of HSP70 epitopes to the L1-L2-E7 DNA construct significantly increased the gene expression. Moreover, the HSP70-L1-L2-E7 DNA construct could significantly increase immune responses toward Th1 response and CTL activity, and induce stronger antitumor effects in mouse model. Thus, the designed HSP70-L1-L2-E7 DNA construct represents promising results for development of HPV DNA vaccine candidates. KeywordsHuman papillomavirus • Early protein • Late protein • Immunoinformatics tools • Multiepitope DNA vaccine * Azam Bolhassani

Immunoinformatics studies of heat shock proteins 27 and 70: Development of potent therapeutic vaccine constructs against human papillomavirus-related cancers

“…In silico tools for the design of immunogenic multiepitope constructs reduce the time and cost of experimental testing. Identification of T-cell epitopes is one of the most important steps in determining the immunodominant regions of a protein [ 21 ]. For eliciting the most effective immune response, these epitopes should mimic natural immunity, and interact with both MHC class I and II molecules [ 22 ].…”

“…Regarding that CD4 + T-cell activation requires a good binding of HTL epitope to MHC-II [ 21 ], four T-cell epitope prediction tools including NetMHCIIpan 4.0 ( http://www.cbs.dtu.dk/services/NetMHCIIpan/ ), IEDB ( http://tools.iedb.org/mhcii/ ), Syfpeithi ( http://www.syfpeithi.de/bin/MHCServer.dll/EpitopePrediction.htm ), and ProPred ( http://crdd.osdd.net/raghava/propred/ ) web servers with default parameters were used to predict interactions between HTL epitopes (14–16 residues) and frequent MHC-II alleles. Potential HTL epitopes with the best binding affinity to prevalent MHC-II alleles in human and mouse were selected by four prediction tools.…”

Progress and prospects on vaccine development against monkeypox infection

“…Highly active expression vectors based on those created for synthesizing recombinant proteins are used to get the most extraordinary immune responses. DNA vaccines have been explored against various viral, bacterial, and parasitic infections due to their simplicity in development and testing [ [147] , [148] , [149] ].…”

New Perspectives in Therapeutic Vaccines for HPV: A Critical Review

“…The main cause involved in cervical cancer development is Human Papillomavirus (HPV), which represents the most common sexually transmitted infection [ 3 ], and more than 200 genotypes were recognized, but alone, HPV16 and HPV18 cause 70% of cervical cancers [ 4 , 5 , 6 ].…”

“…HPV-associated cancers also include squamous cell carcinoma of the oropharynx, anus, rectum, penis, vagina, and vulva [ 2 , 7 ]. In relation to HPV role in oncogenesis, considerable effort has been made to control HPV-induced diseases using prophylactic or therapeutic approaches [ 6 ].…”