Perspective of Peptide Vaccine Composed of Epitope Peptide, CpG-DNA, and Liposome Complex Without Carriers

Lee, Younghee; Lee, Young Seek; Cho, Soo Young; Kwon, Hyung‐Joo

doi:10.1016/bs.apcsb.2015.03.004

Cited by 10 publications

(9 citation statements)

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“…Three peptides (2, 9, and 41) were eliminated from further consideration due to similarities (.50% sequence identity) with human proteins including rootletin (Ciliary rootlet coiled-coil protein), Dynactin 1, B cell receptor associated protein 29, microtubule-actin cross linking factor 1, and myosin (heavy polypeptide 7B, cardiac muscle, b, Isoform CRA_c). Hence, seven peptides emerged from the primary screen (5,6,11,13,40, 66, and 72), which involved mutations at four positions: S1E, S1V, R2N, R2D, K6N, K10R, and K10M within the p145 minimal epitope (Fig. 1C).…”

Section: Resultsmentioning

confidence: 99%

Enhancing Vaccine Efficacy by Engineering a Complex Synthetic Peptide To Become a Super Immunogen

Nordström

Pandey

Calcutt

et al. 2017

The Journal of Immunology

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Peptides offer enormous promise as vaccines to prevent and protect against many infectious and noninfectious diseases. However, to date, limited vaccine efficacy has been reported and none have been licensed for human use. Innovative ways to enhance their immunogenicity are being tested, but rational sequence modification as a means to improve immune responsiveness has been neglected. Our objective was to establish a two-step generic protocol to modify defined amino acids of a helical peptide epitope to create a superior immunogen. Peptide variants of p145, a conserved helical peptide epitope from the M protein of , were designed by exchanging one amino acid at a time, without altering their α-helical structure, which is required for correct antigenicity. The immunogenicities of new peptides were assessed in outbred mice. Vaccine efficacy was assessed in a skin challenge and invasive disease model. Out of 86 variants of p145, seven amino acid substitutions were selected and made the basis of the design for 18 new peptides. Of these, 13 were more immunogenic than p145; 7 induced Abs with significantly higher affinity for p145 than Abs induced by p145 itself; and 1 peptide induced more than 10,000-fold greater protection following challenge than the parent peptide. This peptide also only required a single immunization (compared with three immunizations with the parent peptide) to induce complete protection against invasive streptococcal disease. This study defines a strategy to rationally improve the immunogenicity of peptides and will have broad applicability to the development of vaccines for infectious and noninfectious diseases.

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Section: Resultsmentioning

confidence: 99%

Enhancing Vaccine Efficacy by Engineering a Complex Synthetic Peptide To Become a Super Immunogen

Nordström

Pandey

Calcutt

et al. 2017

The Journal of Immunology

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“…), chemokines (MIP-2, MCP-1, RANTES, IP-10, etc. ), MHC class II molecules, and co-stimulatory molecules (CD40, CD80, CD83, CD86) is stimulated [74]. In an early work [75], immunization of mice with a mixture of CpG-ODN and liposomes (PC-PG-Chol, 2 : 0.2 : 1) encapsulating the MHC class Irestricted OVA and gp33 peptide epitopes activated maturation of DCs, promoted cross-presentation, and induction of an immune response along the T H 1 pathway.…”

Section: Effect Of Immunostimulatory Molecules (Prr Ligands)mentioning

confidence: 99%

“…Synthetic CpG ODNs are successfully used in the design of liposomal vaccines. The immunostimulant can be co-encapsulated in the internal aqueous volume of liposomes or adsorbed on surface of cationic liposomes [74,76,77]. Recently, a new platform for the development of vaccines has been proposed: a covalent conjugate of CpG-ODN with a conserved Streptococcus agalactiae (a group B streptococcus) pili protein was adsorbed onto cationic liposomes.…”

Section: Effect Of Immunostimulatory Molecules (Prr Ligands)mentioning

confidence: 99%

“…The incorporation of antigens, particularly peptides, in the form of lipid conjugates with into the liposome membrane solves these problems. In recent years, interest in liposome-based peptide vaccines has grown [41,43,74,99]. This is due to (1) the development of powerful bioinformatics resources, which can significantly reduce the time and labor costs for the search for new epitopes of biological targets, and (2) improvement of technologies for solid-phase chemical synthesis of peptides.…”

Section: Liposomal Vaccines Carrying the Antigen-lipid Conjugatesmentioning

confidence: 99%

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Liposomes as Adjuvants and Vaccine Delivery Systems

Tretiakova

Водовозова

2022

Biochem. Moscow Suppl. Ser. A

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The review considers liposomes as systems of substantial interest as adjuvant carriers in vaccinology due to their versatility and maximal biocompatibility. Research and development on the use of liposomes and lipid nanoparticles to create subunit vaccines for the prevention and treatment of infectious diseases has been going on for several decades. In recent years, the area has seen serious progress due to the improvement of the technology of industrial production of various high-grade lipids suitable for parenteral administration and the emergence of new technologies and equipment for the production of liposomal preparations. When developing vaccines, it is necessary to take into account how the body's immune system (innate and adaptive immunity) functions. The review briefly describes some of the fundamental mechanisms underlying the mobilization of immunity when encountering an antigen, as well as the influence of liposome carriers on the processes of internalization of antigens by immunocompetent cells and ways of immune response induction. The results of the studies on the interactions of liposomes with antigen-presenting cells in function of the liposome size, charge, and phase state of the bilayer, which depends on the lipid composition, are often contradictory and should be verified in each specific case. The introduction of immunostimulant components into the composition of liposomal vaccine complexes-ligands of the pathogen-associated molecular pattern receptors-permits modulation of the strength and type of the immune response. The review briefly discusses liposomebased vaccines approved for use in the clinic for the treatment and prevention of infectious diseases, including mRNA-loaded lipid nanoparticles. Examples of liposomal vaccines that undergo various stages of clinical trials are presented.

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“…Immune stimulating activity of CpG-DNA was enhanced by encapsulation in a liposome complex consisting of DOPE: cholesterol hemisuccinate (CHEMS) (1:1 ratio). We named CpG-DNA co-encapsulated with DOPE:CHEMS “Lipoplex(O)” 31,32. Liposome complex consisting of B cell epitope and Lipoplex(O) successfully induced antibodies specifically recognizing viral proteins and cancer-associated proteins 31,32…”

Section: Introductionmentioning

confidence: 99%

A peptide-CpG-DNA-liposome complex vaccine targeting TM4SF5 suppresses growth of pancreatic cancer in a mouse allograft model

Jung

Park

et al. 2018

OTT

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BackgroundPatients with pancreatic cancer have a poor prognosis and are usually diagnosed at a late stage. Because TM4SF5 is known to be overexpressed in hepatocellular carcinoma, colon cancer, and pancreatic cancer, it is considered as one of the candidate molecular targets for an anticancer strategies.PurposeThe purpose of this study was to evaluate possible utility of TM4SF5 to treat pancreatic cancer using a mouse allograft model.Materials and methodsWe analyzed expression of TM4SF5 in pancreatic cancer tissues using immunohistochemistry. We established a mouse pancreatic cancer cell line stably expressing TM4SF5 and identified the effect of TM4SF5 expression in vitro. We used the CpG-DNA-peptide-liposome complex as a peptide vaccine and investigated antitumor effects of the vaccine in a mouse model with TM4SF5 expressing pancreatic cells. To investigate the function of produced antibody, we evaluated effects of the anti-TM4SF5 monoclonal antibody in vitro in terms of cell growth and migration properties.ResultsImmunohistochemical analysis showed that 36.4% of pancreatic cancer tissue samples expressed TM4SF5. Expression of TM4SF5 induced increased cell proliferation and motility in vitro. Injection of the TM4SF5 peptide vaccine induced the production of anti-hTM4SF5 antibodies and reduced the growth of pancreatic tumors in mice established by subcutaneous injection of the TM4SF5-expressing mouse pancreatic cancer cell line. The treatment of TM4SF5-expressing cells with the anti-hTM4SF5 monoclonal antibody reduced cell growth, modulated the expression of the epithelial–mesenchymal transition markers Vimentin and E-cadherin, and decreased cell motility in vitro.ConclusionOur results showed that the TM4SF5 peptide vaccine had a protective effect against pancreatic tumors expressing TM4SF5, and this effect was mediated, at least in part, by the production and suppressive function of the anti-TM4SF5 antibodies. Therefore, we suggest that targeting TM4SF5 could be a novel strategy to prevent or treat pancreatic cancer.

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Perspective of Peptide Vaccine Composed of Epitope Peptide, CpG-DNA, and Liposome Complex Without Carriers

Cited by 10 publications

References 121 publications

Enhancing Vaccine Efficacy by Engineering a Complex Synthetic Peptide To Become a Super Immunogen

Enhancing Vaccine Efficacy by Engineering a Complex Synthetic Peptide To Become a Super Immunogen

Liposomes as Adjuvants and Vaccine Delivery Systems

A peptide-CpG-DNA-liposome complex vaccine targeting TM4SF5 suppresses growth of pancreatic cancer in a mouse allograft model

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