Recent Advances in Peptide-Based Subunit Nanovaccines

Skwarczynski, Mariusz; Tóth, István

doi:10.2217/nnm.14.187

Cited by 178 publications

(142 citation statements)

References 81 publications

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“…5 In contrast to whole-cell or protein vaccines, vaccine non-redundant peptide components are non-toxic and non-infectious, and significantly lower the risks of allergic and/or autoimmune responses in patients. 6 They have high specificity as their peptide epitopes are purposely designed to recognize certain pathogenic targets. The pure peptides are easily produced under simple and economical methods, and microbe culturing is not required.…”

Section: Introductionmentioning

confidence: 99%

“…Commercially available adjuvants are often weak inducers of anticancer immune responses and/or toxic, and, therefore, new delivery platforms/adjuvants are needed. 6,7 To be effective, a therapeutic vaccine must be able to induce antitumor T-lymphocyte responses to directly kill cancer cells and, subsequently, to regress tumor growth. 8 The identification of appropriate peptide epitopes capable of initiating effective antitumor Tlymphocyte responses is critical for the design of a therapeutic vaccine.…”

Section: Introductionmentioning

confidence: 99%

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Multiantigenic peptide–polymer conjugates as therapeutic vaccines against cervical cancer

Hussein

Liu

Jia

et al. 2016

Bioorganic & Medicinal Chemistry

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Immunotherapy is one of the most promising strategies for the treatment of cancer. Human papillomavirus (HPV) is responsible for virtually all cases of cervical cancer. The main purpose of a therapeutic HPV vaccine is to stimulate CD8 + cytotoxic T lymphocytes (CTLs) that can eradicate HPV infected cells. HPV oncoproteins E6 and E7 are continuously expressed and are essential for maintaining the growth of HPV-associated tumor cells. We designed polymer-based multi-antigenic formulations/constructs that were comprised of the E6 and E7 peptide epitopes.We developed an N-terminus-based epitope conjugation to conjugate two unprotected peptides to poly tert-butyl acrylate. This method allowed for the incorporation of the two antigens into a polymeric dendrimer in a strictly equimolar ratio. The most effective formulations eliminated tumors in up to 50% of treated mice. Tumor recurrence was not observed up to 3 months post initial challenge.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Multiantigenic peptide–polymer conjugates as therapeutic vaccines against cervical cancer

Hussein

Liu

Jia

et al. 2016

Bioorganic & Medicinal Chemistry

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“…One of the directions for vaccine development is the use of conserved B-cell epitopes from the M-protein (e.g. J14) [5,18,19]. However, peptide-based vaccines are not immunogenic and require the addition of adjuvants or a delivery system for optimum efficacy.…”

Section: Resultsmentioning

confidence: 99%

“…Due to its antiphagocytic function, the GAS cell-surface M-protein is a major virulence factor inGAS infections. However, the use of whole proteins as a vaccine component may be associated with several disadvantages, such as the presence of impurities, unwanted side effects, allergies and manufacturing difficulties [5]. Importantly, some fragments of M-proteins could induce an autoimmune response.…”

Section: Introductionmentioning

confidence: 99%

Poly-L-lysine-coated nanoparticles are ineffective in inducing mucosal immunity against group a streptococcus

Marasini¹,

Giddam²,

Batzloff³

et al. 2017

Bio Chem Comp

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Background: Group A Streptococcus (GAS) can cause a range of maladies, from simple throat infections to lethal complication, such as rheumatic heart disease. The M-protein, a bacterial cell surface protein, is the major virulence factor ofGAS. Several attempts have been made over the past few decades to develop vaccines against GASthat employed peptides derived from the M-protein. One suchapproach used lipopeptides or lipid core peptide (LCP) systems that incorporated a B-cell epitope derived from the conserved region of the M-protein. Methods:In the present study, we prepared different biodegradable polymer [dextran, poly-(lacticcoglycolic-acid) (PLGA), and poly-L-lysine] nanoparticles (NPs)-based delivery systems for a lipopeptidevaccine candidate (LCP-1).The NPs were characterised by their size, charge, morphology, antigen-presenting cells (APCs) uptake and subsequent APCs maturations efficacy, followed by in vivo nasal immunisation in mice. Results:All produced NPs ranged in size from 100-205 nm, and their charge varied depending upon the nature of polymer. A high APCs uptake efficacy for dextran and poly-L-lysine NPswere observed, compared to PLGA NPs. Despite the high uptake by APCs, dextran and poly-L-lysine NPs failed to improve APCs maturation that resulted in low antibody titres. In contrast, while LCP-1 encapsulated into PLGA showed low APCs uptake,it induced significant maturation of DCs and higher antibody titres compared to other NPs. Conclusions: Positively-charged poly-L-lysine NPswere non-immunogenic, while negatively charged PLGA NPs induced similar responses to antigens adjuvanted with cholera toxin B (CTB).

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“…Importantly, peptide-based vaccines can be designed to stimulate only the desired immune response and can even trigger protective immune responses more efficiently than whole protein-based approaches [15,16]. In addition, peptide-based vaccines can be produced easily in large-scale with high purity, freeze-dried, stored in solid form and customized for an appropriate immune response [17]. However, peptides by themselves are not immunogenic and to overcome this problem an adjuvant or appropriate delivery system is necessary [18,19].…”

Section: Biochemical Compoundsmentioning

confidence: 99%

Synthesis and immunological evaluation of peptide-based vaccine candidates against malaria

Chandrudu¹,

Skwarczynski²,

Pattinson³

et al. 2016

Bio Chem Comp

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Background: Malaria, caused by the protozoan parasite Plasmodium, is one of the main causes of morbidity and mortality of the whole human population.Intensive, ongoing research aims to develop an effective vaccine against malaria; however, it has been unsuccessful for over a century. The circumsporozoite protein (CSP) plays crucial a role in the parasite life cycle. CSP is the most dominant surface antigen of the initial pre-erythrocytic stage. We designed vaccine constructs using four different CD4 + and CD8 + T cell epitopes derived from the CSP and used the lipid core peptide (LCP) as a self-adjuvanting delivery system. Methods: All the constructs were synthesized using microwave-assisted solid phase peptide synthesis (SPPS). Immunological evaluation was carried out following subcutaneous administration of LCP-based vaccine candidates in a BALB/c mouse model. Interferon gamma (IFN-γ) production was used to measure the induction of epitope-specific cellular immune responses after vaccination. Results: Self-adjuvanting LCP malaria vaccines composed of different epitopes were synthesized.To determine whether the vaccine candidates were able to induce cellular immunity, mice were immunized with LCP constructs or peptide epitopes adjuvanted with cholera toxin.Two of the tested constructs induced a high level of INF-γ in mice after subcutaneous immunization. Conclusions: We have demonstrated here for the first time that the LCP delivery system induced epitopespecific cellular immune responses against an antigen derived from Plasmodium.

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Recent Advances in Peptide-Based Subunit Nanovaccines

Cited by 178 publications

References 81 publications

Multiantigenic peptide–polymer conjugates as therapeutic vaccines against cervical cancer

Multiantigenic peptide–polymer conjugates as therapeutic vaccines against cervical cancer

Poly-L-lysine-coated nanoparticles are ineffective in inducing mucosal immunity against group a streptococcus

Synthesis and immunological evaluation of peptide-based vaccine candidates against malaria

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