Double conjugation strategy to incorporate lipid adjuvants into multiantigenic vaccines

Hussein, Waleed M.; Liu, Tzu-Yu; Maruthayanar, Pirashanthini; Mukaida, Saori; Moyle, Peter M.; Wells, James W.; Tóth, István; Skwarczynski, Mariusz

doi:10.1039/c5sc03859f

Cited by 25 publications

(32 citation statements)

References 44 publications

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“…Thus, to achieve a well-defined vaccine candidate in a reproducible manner, a recently developed double conjugation strategy was proposed. 20 First, an acryloyl derivative of E6 43-57 (13) was conjugated to the mercapto-azide derivative of E7 44-57 (14) at pH ~7.3 to produce compound 15 in 90% yield (Scheme 3). 20 The azide 15 was then conjugated to the dendrimer 8 in the presence of Cu wire to give 7 (Scheme 3).…”

Section: Synthesis and Characterization Of Polymer-peptide Conjugatesmentioning

confidence: 99%

“…20 First, an acryloyl derivative of E6 43-57 (13) was conjugated to the mercapto-azide derivative of E7 44-57 (14) at pH ~7.3 to produce compound 15 in 90% yield (Scheme 3). 20 The azide 15 was then conjugated to the dendrimer 8 in the presence of Cu wire to give 7 (Scheme 3). Vaccine candidates 1-7 were all self-assembled into particles via the solvent replacement method (DMF/water).…”

Section: Synthesis and Characterization Of Polymer-peptide Conjugatesmentioning

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: Synthesis and Characterization Of Polymer-peptide Conjugatesmentioning

confidence: 99%

Section: Synthesis and Characterization Of Polymer-peptide Conjugatesmentioning

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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“…Recently, Hussein conjugated different lipidic moieties (7 and 10) to HPV cytotoxic T lymphocyte (CTL) epitopes E6 [43][44][45][46][47][48][49][50][51][52][53][54][55][56][57] (QLLRREVYDFAFRDL) and 8Q min to produce self-assembled nanovaccines (see Fig. 4) [108]. 10-(8Q min )E6 [43][44][45][46][47][48][49][50][51][52][53][54][55][56][57] formed 350-750 nm nanoparticles, while 7-(8Q min )E6 [43][44][45][46][47][48][49][50][51][52][53][54][55][56][57] formed much larger particles (> 5 μm).…”

Section: Lipid-based Self-assembled Nanostructurementioning

confidence: 99%

The application of self-assembled nanostructures in peptide-based subunit vaccine development

Zhao

Chandrudu

Skwarczynski

et al. 2017

European Polymer Journal

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Please cite this article as: Zhao, G., Chandrudu, S., Skwarczynski, M., Toth, I., The application of self-assembled nanostructures in peptide-based subunit vaccine development, European Polymer Journal (2017), doi: http:// dx.doi.org/10. 1016/j.eurpolymj.2017.02.014 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. 1The application of self-assembled nanostructures in

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“…Therefore, CD8+ peptide epitopes from E7 capable of activating CTLs are commonly used to develop vaccines against cervical cancer. [5][6][7][8][9] In general, peptides alone are unable to stimulate the immune system because of their poor immunogenic properties; therefore, their integration with appropriate adjuvants and/or a delivery system is required. 10 Unfortunately, many adjuvants are toxic, unsuitable for human use, or too weak to stimulate immune responses against weak peptide antigens.…”

Section: Introductionmentioning

confidence: 99%

Liposomal formulation of polyacrylate-peptide conjugate as a new vaccine candidate against cervical cancer

Tóth¹,

Khongkow²,

Liu³

et al. 2018

prnano

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Peptide-based vaccines have been proposed as a therapeutic strategy for many infectious diseases, including human papilloma virus (HPV)-related cervical cancer. Peptide-based vaccines are a better treatment option than traditional chemotherapeutic agents and surgery, as they rely on the use of the body’s immune system to fight cancer cells, resulting in minimal risk of side effects. However, to increase the efficacy of peptide-based vaccines, the application of potent adjuvant and a suitable delivery system is essential. In this study, we developed a self-adjuvanting delivery system based on a combination of polymer and liposomes, for a therapeutic vaccine against cervical cancer. Peptide epitope (8Qm) derived from HPV-16 E7 protein was conjugated to dendritic poly(tert-butyl acrylate) as a primary delivery system and incorporated into cationic liposomes, which served as a secondary delivery system. Our vaccine candidate was able to kill established HPV-16 E7-positive tumor (TC-1) cells in mice following a single immunization. The immunized mice had 80% survival rate after two months. In contrast, both polymer-8Qm conjugate and liposomes bearing 8Qm failed to eradicate TC-1 tumors. The survival rate of mice was only 20% when immunized with 8Qm formulated with standard incomplete Freund’s adjuvant.

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Double conjugation strategy to incorporate lipid adjuvants into multiantigenic vaccines

Abstract: Conjugation of multiple peptides by their N-termini is a promising technique to produce branched multiantigenic vaccines.

Cited by 25 publications

References 44 publications

Multiantigenic peptide–polymer conjugates as therapeutic vaccines against cervical cancer

Multiantigenic peptide–polymer conjugates as therapeutic vaccines against cervical cancer

The application of self-assembled nanostructures in peptide-based subunit vaccine development

Liposomal formulation of polyacrylate-peptide conjugate as a new vaccine candidate against cervical cancer

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