Effects of the Chemical Structures of Oligoarginines Conjugated to Biocompatible Polymers as a Mucosal Adjuvant on Antibody Induction in Nasal Cavities

Mohri, Kunihiko; Miyata, Koichiro; Egawa, Tomomi; Tanishita, Sohei; Endo, Rikito; Yagi, Haruya; Ukawa, Masami; Ochiai, Kyohei; Hiwatari, Ken‐ichiro; Tsubaki, Kazufumi; Shigeno, Koichi; Tobita, Etsuo; Uto, Takuhiro; Baba, Masanori; Sakuma, Shinji

doi:10.1248/cpb.c17-00834

Cited by 12 publications

(20 citation statements)

References 28 publications

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“… a Both oligoarginine-linked PNVA- co -AAs were characterized in the previous study (weight-average molecular weight (Mw) of PNVA- co -AA, 350 kDa; NVA units/AA units of PNVA- co -AA, 70/30) b Percentage of the number of the respective monomer units to the total number of monomer units. c Weight percentage of oligoarginines grafted onto polymers (oligoarginines excluding glycine segments/oligoarginine-linked polymers). d Mw of oligoarginine-linked polymers calculated on the basis of Mw of original polymers (hyaluronic acid, 27 kDa; PNVA- co -AA, 350 kDa), Mw of oligoarginines, and the grafting degree. …”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Mice immunized with inactivated PRI viruses in the presence of d -octaarginine-linked PNVA- co -AA were perfectly protected from infection with mouse-adapted PRI viruses; however, a similar protection against a homologous virus infection was not observed when mice were immunized with the antigen alone . Adjuvant activities of d -octaarginine-linked PNVA- co -AA also increased with an elevation of the grafting degree of the peptide onto the polymeric backbone …”

Section: Introductionmentioning

confidence: 95%

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Biodegradable Hyaluronic Acid Modified with Tetraglycine-l-octaarginine as a Safe Adjuvant for Mucosal Vaccination

et al. 2019

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We have been investigating the potential use of polymers modified with cell-penetrating peptides as an adjuvant for mucosal vaccination and have already developed nondegradable poly(N-vinylacetamide-co-acrylic acid) (PNVA-co-AA) with which D-octaarginine, a typical cell-penetrating peptide, was grafted. Our previous murine infection experiments demonstrated that immunoglobulin G (IgG) and immunoglobulin A (IgA) were induced in systemic circulation and secreted on nasal mucosa, respectively, through 4-time nasal inoculations with a mixture of influenza viral antigens and D-octaarginine-linked PNVA-co-AA at 7-day intervals, and that immunized mice were perfectly protected from homologous virus infection. In the present study, we designed novel biodegradable polymers bearing cell-penetrating peptides from a perspective of clinical application. Hyaluronic acid whose glucuronic acid was modified with tetraglycine-L-octaarginine at a monosaccharide unit ratio of 30% was successfully developed. The hyaluronic acid derivative exhibited adjuvant activities identical to PNVA-co-AA bearing either D-octaarginine or tetraglycine-D-octaarginine under the above-mentioned inoculation schedule. We further found that there was no difference in humoral immunity between the 4-time inoculations at 7-day intervals and the 2-time inoculations at 28-day intervals. Intranasal IgA induced through the latter schedule with a smaller number of inoculations, which is clinically practical, exhibited cross-reactivity beyond the subtype of viral strains. In vitro toxicity studies demonstrated that the hyaluronic acid derivative was much less toxic than the corresponding PNVA-co-AA derivatives, and that both the polymers and their metabolites did not exhibit genotoxicity. Our results suggested that tetraglycine-L-octaarginine-linked hyaluronic acid would be a clinically valuable and safe adjuvant for mucosal vaccination.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

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Biodegradable Hyaluronic Acid Modified with Tetraglycine-l-octaarginine as a Safe Adjuvant for Mucosal Vaccination

et al. 2019

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“…In contrast, mice immunized with polyarginine-PNVA-co-AA containing antigenic influenza virus hemagglutinin (HA) protein induced both mucosal and systemic immune responses against influenza virus, similar to those of HA protein administered with CTB. Upon introduction of linker between polyarginine and PNVA-co-AA further, increase of HA protein-specific IgA titers was observed [97].…”

Section: Applications Of Cpps In Vaccine Deliverymentioning

confidence: 99%

Cell-penetrating Peptides: Efficient Vectors for Vaccine Delivery

Yang

Luo

Shibu

et al. 2019

CDD

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Subunit vaccines are composed of pathogen fragments that, on their own, are generally poorly immunogenic. Therefore, the incorporation of an immunostimulating agent, e.g. adjuvant, into vaccine formulation is required. However, there are only a limited number of licenced adjuvants and their immunostimulating ability is often limited, while their toxicity can be substantial. To overcome these problems, a variety of vaccine delivery systems have been proposed. Most of them are designed to improve the stability of antigen in vivo and its delivery into immune cells. Cell-penetrating peptides (CPPs) are especially attractive component of antigen delivery systems as they have been widely used to enhance drug transport into the cells. Fusing or co-delivery of antigen with CPPs can enhance antigen uptake, processing and presentation by antigen presenting cells (APCs), which are the fundamental steps in initiating an immune response. This review describes the different mechanisms of CPP intercellular uptake and various CPP-based vaccine delivery strategies.

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“…CPPs have also been incorporated into other delivery systems, especially nanoparticles [5,11,12]. For example, the TAT synthetic analog, polyarginine, was conjugated to N-vinylacetamide-co-acrylic acid (VA-AA) and administered to mice with influenza virus antigens [13]. The strongest immune responses were observed when a linker between polyarginine and VA-AA was introduced, which influenced grafting efficacy of VA-AA with polyarginine, ζ-potential of formed nanoparticles and presumably conformation of polyarginine unit, demonstrating that how CPP is incorporated into the delivery system is also important.…”

mentioning

confidence: 99%

Cell-penetrating Peptides in Vaccine Delivery: facts, Challenges and Perspectives

Skwarczynski

Tóth

2019

Ther. Deliv.

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Effects of the Chemical Structures of Oligoarginines Conjugated to Biocompatible Polymers as a Mucosal Adjuvant on Antibody Induction in Nasal Cavities

Cited by 12 publications

References 28 publications

Biodegradable Hyaluronic Acid Modified with Tetraglycine-l-octaarginine as a Safe Adjuvant for Mucosal Vaccination

Biodegradable Hyaluronic Acid Modified with Tetraglycine-l-octaarginine as a Safe Adjuvant for Mucosal Vaccination

Cell-penetrating Peptides: Efficient Vectors for Vaccine Delivery

Cell-penetrating Peptides in Vaccine Delivery: facts, Challenges and Perspectives

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