Poly[di(sodium carboxylatoethylphenoxy)phosphazene] (PCEP) is a potent enhancer of mixed Th1/Th2 immune responses in mice immunized with influenza virus antigens

Mutwiri, George; Benjamin, Philip; Soita, H. W.; Townsend, H. G. G.; Yost, Richard; Roberts, Bryan E.; Andrianov, Alexander K.; Babiuk, Lorne A.

doi:10.1016/j.vaccine.2006.10.011

Cited by 104 publications

(102 citation statements)

References 17 publications

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“…antigens and other adjuvants, increasing their stability and allowing for multimeric presentation. Delivery of antigens formulated with PP has been successful in enhancing antibody responses to influenza (Mutwiri et al, 2007;Payne et al, 1995), rotavirus (McNeal et al, 1999 and cholera (Wu et al, 2001). Protection was also enhanced in the latter two models.…”

Section: Introductionmentioning

confidence: 99%

Intranasal immunization of mice with a formalin-inactivated bovine respiratory syncytial virus vaccine co-formulated with CpG oligodeoxynucleotides and polyphosphazenes results in enhanced protection

Mapletoft

Oumouna

Kovacs-Nolan

et al. 2008

Journal of General Virology

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As respiratory syncytial virus (RSV) targets the mucosal surfaces of the respiratory tract, induction of both systemic and mucosal immunity will be critical for optimal protection. In this study, the ability of an intranasally delivered, formalin-inactivated bovine RSV (FI-BRSV) vaccine co-formulated with CpG oligodeoxynucleotides (ODN) and polyphosphazenes (PP) to induce systemic and mucosal immunity, as well as protection from BRSV challenge, was evaluated. Intranasal immunization of mice with FI-BRSV formulated with CpG ODN and PP resulted in both humoral and cell-mediated immunity, characterized by enhanced production of BRSV-specific serum IgG, as well as increased gamma interferon and decreased interleukin-5 production by in vitro-restimulated splenocytes. These mice also developed mucosal immune responses, as was evident from increased production of BRSV-specific IgG and IgA in lung-fragment cultures. Indeed, the increases in serum and mucosal IgG, and in particular mucosal IgA and virusneutralizing antibodies, were the most critical differences observed between FI-BRSV formulated with both CpG ODN and PP in comparison to formulations with CpG ODN, non-CpG ODN or PP individually. Finally, FI-BRSV/CpG/PP was the only formulation that resulted in a significant reduction in viral replication upon BRSV challenge. Co-formulation of CpG ODN and PP is a promising new vaccine platform technology that may have applications in mucosal immunization in humans. INTRODUCTIONHuman respiratory syncytial virus (HRSV) is a leading cause of respiratory disease in infants and young children worldwide (Heilman, 1990) and is responsible for significant economic loss; in the year 2000 alone, there were 86 000 HRSV infection-related hospitalizations in the USA, costing a total of $394 000 000 (Paramore et al., 2004). Nearly 98 % of these hospitalizations occurred in children under 5 years old. Between 1997 and 2000, HRSV bronchiolitis was the leading cause of infant hospitalization and, in 1999, an estimated 360 HRSV-associated postneonatal deaths (i.e. in children aged between 28 days and 1 year) occurred in the USA (Leader & Kohlhase, 2003).Like HRSV, bovine respiratory syncytial virus (BRSV) is an enveloped, non-segmented, single-stranded RNA pneumovirus of the family Paramyxoviridae and order Mononegavirales. BRSV is responsible for significant economic loss to the cattle industry (Stott & Taylor, 1985) and is one of the four known viral components of bovine shipping fever. HRSV and BRSV have similar clinical outcomes in their respective host species, ranging from asymptomatic infection to bronchiolitis and pneumonia, and sometimes death (Philippou et al., 2000). The distribution of both viruses is worldwide.Whilst there are several commercial BRSV vaccines currently available for immunizing cattle, better vaccines that are more efficacious in the face of maternal antibodies and that induce longer-lasting protection would be desirable. Also, there is currently no safe and effective vaccine against HRSV available for use in h...

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Section: Introductionmentioning

confidence: 99%

Intranasal immunization of mice with a formalin-inactivated bovine respiratory syncytial virus vaccine co-formulated with CpG oligodeoxynucleotides and polyphosphazenes results in enhanced protection

Mapletoft

Oumouna

Kovacs-Nolan

et al. 2008

Journal of General Virology

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“…Polyphosphazenes are high-molecular weight synthetic polymers consisting of an alternating phosphorus-nitrogen backbone with organic side groups attached to each phosphorous atom [115]. The properties of these macromolecules can be easily modified by the incorporation of different ionic moieties to their structural backbone [115,116].…”

Section: Pcepmentioning

confidence: 99%

“…The properties of these macromolecules can be easily modified by the incorporation of different ionic moieties to their structural backbone [115,116].…”

Section: Pcepmentioning

confidence: 99%

“…According to a number of animal studies, PCEP induces long-lasting immune responses to a variety of bacterial and viral protein antigens [117]. In the context of vaccines, this polyphosphazene has the potential to form noncovalent protein-polymer complexes in solution, promote balanced cell-mediated and humoral immune responses, act as a delivery system, and strongly modulate the early innate immune response at the site of immunization [115,[117][118][119]. In addition, it has been shown that intranasal delivery of PCEP with influenza virus X:31 antigen can induce both systemic and mucosal immune responses in mice [117].…”

Section: Pcepmentioning

confidence: 99%

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Intranasal treatment with a novel immunomodulator mediates innate immune protection against lethal pneumonia virus of mice

et al. 2016

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Respiratory syncytial virus (RSV) is the major causative agent of acute lower respiratory tract infections in infants and young children. Unfortunately, there are no licensed RSV vaccines available, and the few treatment options for high-risk individuals are either extremely costly or cause severe side effects and toxicity. Thus, the development of effective vaccines and therapeutic interventions against RSV is a preeminent public health priority.

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“…It is well documented that several polymeric systems act as adjuvant especially, poly(glycolide) (PGA), 15 poly(lactide-co-glycolide) (PLGA), 16,17 polyacrylic acid (PAA) and its alkyl esters, 18 poloxamers, 19 polyphosphazenes, 20 polyoxyethylene (POE), 21 polyoxypropylene (POP), polyacrylate 22 , and chitosan polymers. 23 These biocompatible and biodegradable polymers have advantages over conventional adjuvants, mainly in the manipulation of degradation kinetics, by varying the concentration of monomers and cross-linkers, 24 thereby modulating the physicochemical properties of polymers and leading to different release profiles of an antigen.…”

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confidence: 99%

Collagen Type II and a Thermo-Responsive Polymer of N-Isopropylacrylamide Induce Arthritis Independent of Toll-Like Receptors

Shakya

Kumar

Klaczkowska

et al. 2011

The American Journal of Pathology

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We established and characterized an arthritis mouse model using collagen type II (CII) and a thermo-responsive polymer, poly(N-isopropylacrylamide) (PNiPAAm). The new PNiPAAm adjuvant is TLR-independent, as all immunized TLR including MyD88-deficient mice developed an anti-CII response. Unlike other adjuvants, PNiPPAm did not skew the cytokine response (IL-1␤, IFN-␥, IL-4, and IL-17), as there was no immune deviation towards any one type of immune spectrum after immunization with CII/ PNiPPAm. Hence, using PNiPAAm, we studied the actual immune response to the self-protein, CII. We observed arthritis and autoimmunity development in several murine strains having different major histocompatibility complex (MHC) haplotypes after CII/ PNiPAAm immunization but with a clear MHC association pattern. Interestingly, C57Bl/6 mice did not develop CII-induced arthritis, with PNiPAAm demonstrating absolute requirement for a classical adjuvant. Presence of a gene (Ncf1) mutation in the NADPH oxidation complex has a profound influence in arthritis and using PNiPAAm we could show that the high CIA severity in Ncf1 mutated mice is independent of any classical adjuvant. Macrophages, neutrophils, eosinophils, and osteoclasts but not mast cells dominated the inflamed joints. Furthermore, arthritis induction in the adjuvant-free, eosinophil-dependent V␤12 DBA/1 mice could be shown to develop arthritis independent of eosinophils using CII/PNiPAAm. Thus, biocompatible and biodegradable PNiPAAm offers unique opportunities to study actual autoimmunity independent of TLR and a particular cytokine phenotype profile.

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Poly[di(sodium carboxylatoethylphenoxy)phosphazene] (PCEP) is a potent enhancer of mixed Th1/Th2 immune responses in mice immunized with influenza virus antigens

Cited by 104 publications

References 17 publications

Intranasal immunization of mice with a formalin-inactivated bovine respiratory syncytial virus vaccine co-formulated with CpG oligodeoxynucleotides and polyphosphazenes results in enhanced protection

Intranasal immunization of mice with a formalin-inactivated bovine respiratory syncytial virus vaccine co-formulated with CpG oligodeoxynucleotides and polyphosphazenes results in enhanced protection

Intranasal treatment with a novel immunomodulator mediates innate immune protection against lethal pneumonia virus of mice

Collagen Type II and a Thermo-Responsive Polymer of N-Isopropylacrylamide Induce Arthritis Independent of Toll-Like Receptors

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