Abstract
Polyphosphazenes are a class of experimental adjuvants that have shown great versatility as vaccine adjuvants in many animal species ranging from laboratory rodents to large animal species. Their adjuvant activity has shown promising results with numerous viral and bacterial antigens, as well as with crude and purified antigens. Vaccines adjuvanted with polyphosphazenes can be delivered via systemic and mucosal administration including respiratory, oral, rectal, and intravaginal routes. Polyphosphazenes can be used in combination with other adjuvants, further enhancing immune responses to antigens. The mechanisms of action of polyphosphazenes have not fully been defined, but several systematic studies have suggested that they act primarily by activating innate immunity. In the present review, we will highlight progress in the development of polyphosphazenes as adjuvants in animals and their other medical applications.
Highlights
Polyphosphazenes are high molecular weight, water-soluble, synthetic polymers that have been investigated for various biomedical applications including tissue regeneration and scaffolding, drug delivery, and stent and denture coatings
Based on evidence from several MOA studies in mice, we have proposed a model to explain the MOA of PCEP, which is summarized in a diagram (Figure 2)
Birds that received CpG ODN + PCEP had a significantly higher survival rate compared to the other groups (55%), and relative risk of mortality was significantly reduced in poly [di(carboxylatophenoxy)phosphazene] (PCPP) (0.25) and PCEP (0.33) formulations as well (Taghavi et al, 2009)
Summary
Polyphosphazenes are high molecular weight, water-soluble, synthetic polymers that have been investigated for various biomedical applications including tissue regeneration and scaffolding, drug delivery, and stent and denture coatings. They have been extensively investigated as adjuvants to improve immune responses to vaccines. Adjuvants are critical components of vaccines because they enhance antigen-specific immune responses that contribute to protection against disease. Polyphosphazenes are a relatively new class of adjuvants that enhance the magnitude, quality and duration of immune responses when co-administered with bacterial and viral antigens in several animal species including mice, pigs, sheep and cattle (McNeal et al, 1999; Andrianov et al, 2006, 2009, 2011; Mutwiri et al, 2007, 2008; Eng et al, 2010; Garlapati et al, 2011; Dar et al, 2012; Magiri et al, 2018). PCEP has been shown to significantly increase IgG1 and IgG2a antibody production compared to PCPP (Mutwiri et al, 2008) and to induce 1,000-fold higher antibody titers compared to alum when co-administered subcutaneously
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