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

Abstract

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.

Evaluation of the effect of MPL and delivery route on immunogenicity and protectivity of different formulations of FimH and MrpH from uropathogenic Escherichia coli and Proteus mirabilis in a UTI mouse model

“…Immunization with MPL and vaccine antigens has been shown to result in a mixed Th1 and Th2 or a shift toward either Th1 or Th2 response and it has been suggested that in addition to the route of administration, variables such as strains of the mice used, type of antigens as well as the concentration of antigen and MPL may affect the Th1/Th2 phenotype [25,26,39,42,43]. Baldridge et al [13] showed that hepatitis B and influenza antigens formulated with MPL and administered IN produced significantly higher IgG2a than IgG1, whereas tetanus toxoid mixed with MPL induced a lower IgG2a than IgG1.…”

Co-delivery of GPI-anchored CCL28 and influenza HA in chimeric virus-like particles induces cross-protective immunity against H3N2 viruses

“…Unfortunately, many mucosal vaccine candidates fail to elicit strong antibody immune responses (67). Thus, there is a great need for mucosal adjuvants as they can break the tolerance and lead to enhanced immune responses.…”

Intranasal vaccination with an adjuvanted polyphosphazenes nanoparticle-based vaccine formulation stimulates protective immune responses in mice

“…Thus, when mice were immunized subcutaneously or intranasally using 50 µg of PCEP in combination with the influenza antigen X:31, PCEP stimulated enhanced production of IgG2a. 47 The same is true when mice received pertussis toxoid in combination with CpG, IDR and 10 µg of PCEP by subcutaneous route. 15 However, only little is known about the quality of the stimulated cellular immune responses following mucosal or parenteral vaccination using polyphosphazenes as adjuvant carrier system.…”