Adjuvants for influenza vaccine

Cam, Nancy N Bouveret le; Ronco, J.; Françon, Alain; Blondeau, Christine; Fanget, B.

doi:10.1016/s0923-2494(98)80037-0

Cited by 26 publications

(3 citation statements)

References 6 publications

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“…In addition, PCPP has been safely tested in Phase I clinical trials as an adjuvant with an influenza vaccine on young and elderly human adults with enhanced immune responses in sera and no side effects [45]. PCPP also been used in clinical trials on a HIV vaccine [46].…”

Section: Discussionmentioning

confidence: 99%

PCEP enhances IgA mucosal immune responses in mice following different immunization routes with influenza virus antigens

Eng

Garlapati

Gerdts

et al. 2010

J Immune Based Ther Vaccines

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BackgroundWe previously demonstrated that polyphosphazenes, particularly PCEP, enhance immune responses in mice immunized subcutaneously and intranasally. The objective of the present study was to investigate the efficacy of polyphosphazenes as adjuvants when delivered through different routes of vaccine administration.MethodsBALB/c mice were immunized through intranasal, subcutaneous, oral and intrarectal delivery with vaccine formulations containing either influenza X:31 antigen alone or formulated in PCEP. Serum and mucosal washes were collected and assayed for antigen-specific antibody responses by ELISA, while splenocytes were assayed for antigen-specific cytokine production by ELISPOT.ResultsIntranasal immunization with PCEP+X:31 induced significantly higher IgA titers in all mucosal secretions (lung, nasal, and vaginal) compared to the other routes. Serum analysis showed that all mice given the PCEP+X:31 combination showed evidence of enhanced IgG2a titers in all administered routes, indicating that PCEP can be effective as an adjuvant in enhancing systemic immune responses when delivered via different routes of administration.ConclusionsWe conclude that PCEP is a potent and versatile mucosal adjuvant that can be administered in a variety of routes and effectively enhances systemic and local immune responses. Furthermore, intranasal immunization was found to be the best administration route for enhancing IgA titers, providing further evidence for the potential of PCEP as a mucosal adjuvant.

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Section: Discussionmentioning

confidence: 99%

PCEP enhances IgA mucosal immune responses in mice following different immunization routes with influenza virus antigens

Eng

Garlapati

Gerdts

et al. 2010

J Immune Based Ther Vaccines

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“…The exact reasons for this are yet not fully understood [174], but it would appear that the high density of binding sites and high conformational adaptability of the PPz main chain can aid protein binding and presentation [167]. The most investigated structures, PCPP and poly[di(sodium carboxylatoethylphenoxy)phosphazene] (PCEP) (Figure 39), have shown positive results in combination with a diverse range of antigens in large animals [175,176] and phase I and phase II clinical trials in humans [174,177,178], and they have been developed as microneedle patches [179,180] for intradermal administration. Chemical structures of some polyacid poly(organo)phosphazenes.…”

Section: Vaccine Adjuvantsmentioning

confidence: 99%

Main-Chain Phosphorus-Containing Polymers for Therapeutic Applications

Strasser

Teasdale

2020

Molecules

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Polymers in which phosphorus is an integral part of the main chain, including polyphosphazenes and polyphosphoesters, have been widely investigated in recent years for their potential in a number of therapeutic applications. Phosphorus, as the central feature of these polymers, endears the chemical functionalization, and in some cases (bio)degradability, to facilitate their use in such therapeutic formulations. Recent advances in the synthetic polymer chemistry have allowed for controlled synthesis methods in order to prepare the complex macromolecular structures required, alongside the control and reproducibility desired for such medical applications. While the main polymer families described herein, polyphosphazenes and polyphosphoesters and their analogues, as well as phosphorus-based dendrimers, have hitherto predominantly been investigated in isolation from one another, this review aims to highlight and bring together some of this research. In doing so, the focus is placed on the essential, and often mutual, design features and structure–property relationships that allow the preparation of such functional materials. The first part of the review details the relevant features of phosphorus-containing polymers in respect to their use in therapeutic applications, while the second part highlights some recent and innovative applications, offering insights into the most state-of-the-art research on phosphorus-based polymers in a therapeutic context.

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“…Water-soluble ionic polyphosphazenes—hybrid organic–inorganic macromolecules—are potent vaccine adjuvants which realize in vivo activity via synergistic antigen delivery and immunostimulation mechanisms [ 14 , 15 ]. Poly[di(carboxylatophenoxy)phosphazene] (PCPP) is an important representative of this class of immunoadjuvants, which has demonstrated its safety and potency in clinical trials [ 16 , 17 , 18 , 19 ] and continues to show significant potential with newly emerging antigens or with alternative administration routes, such as microneedle-based intradermal vaccination [ 20 , 21 , 22 , 23 , 24 , 25 ]. The ability of PCPP to promote immune responses of enhanced magnitude, breadth and durability is closely associated with its exceptional capability to spontaneously self-assemble with antigenic proteins under physiological conditions [ 21 , 25 , 26 , 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

Fluorine-Functionalized Polyphosphazene Immunoadjuvant: Synthesis, Solution Behavior and In Vivo Potency

et al. 2023

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The inclusion of fluorine motifs in drugs and drug delivery systems is an established tool for modulating their biological potency. Fluorination can improve drug specificity or boost the vehicle’s ability to cross cellular membranes. However, the approach has yet to be applied to vaccine adjuvants. Herein, the synthesis of fluorinated bioisostere of a clinical stage immunoadjuvant—poly[di(carboxylatophenoxy)phosphazene], PCPP—is reported. The structure of water-soluble fluoropolymer—PCPP-F, which contains two fluorine atoms per repeat unit—was confirmed using 1H, 31P and 19F NMR, and its molecular mass and molecular dimensions were determined using size-exclusion chromatography and dynamic light scattering. Insertion of fluorine atoms in the polymer side group resulted in an improved solubility in acidic solutions and faster hydrolytic degradation rate, while the ability to self-assemble with an antigenic protein, lysozyme—an important feature of polyphosphazene vaccine adjuvants—was preserved. In vivo assessment of PCPP-F demonstrated its greater ability to induce antibody responses to Hepatitis C virus antigen when compared to its non-fluorinated counterpart. Taken together, the superior immunoadjuvant activity of PCPP-F, along with its improved formulation characteristics, demonstrate advantages of the fluorination approach for the development of this family of macromolecular vaccine adjuvants.

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Adjuvants for influenza vaccine

Cited by 26 publications

References 6 publications

PCEP enhances IgA mucosal immune responses in mice following different immunization routes with influenza virus antigens

PCEP enhances IgA mucosal immune responses in mice following different immunization routes with influenza virus antigens

Main-Chain Phosphorus-Containing Polymers for Therapeutic Applications

Fluorine-Functionalized Polyphosphazene Immunoadjuvant: Synthesis, Solution Behavior and In Vivo Potency

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