Efficacy of poly[di(sodium carboxylatophenoxy)phosphazene] (PCPP) as mucosal adjuvant to induce protective immunity against respiratory pathogens.
Polyphosphazene polyelectrolyte, a potent new mucosal adjuvant candidate, was tested for its ability to elicit protective immunity against several respiratory diseases. Groups of mice were intranasally (i.n.) vaccinated with poly[di(sodium carboxylatophenoxy)phosphazene] (PCPP) together with several vaccine antigens such as pertussis toxoid, pneumococcal surface protein A, and formalin-inactivated PR8 influenza virus. Results showed predominant levels of antigen-specific IgG and IgA antibodies in serum and bronchial alveolar lavage fluids after vaccination with PCPP plus antigen when compared to antigen alone. In addition, there were significantly higher levels of the secretory form of IgA antibody in the mucosal secretions (i.e., nasal wash, saliva, vaginal wash, and fecal extracts). Moreover, i.n. vaccination with PCPP resulted in brisk numbers of IgG and IgA antibody-forming cells in the nasal passage, lung, and sub-mandibular glands of vaccinated mice. Of note, PCPP administration resulted in mixed Th1 and Th2 type responses (i.e., high levels of IgG2a and IgG1 as well as IFN-gamma and IL-4). Most interestingly, i.n. challenge with vaccine antigens together with PCPP elicited strong protective efficacy against respiratory infection with Bordetella pertussis, Streptococcus pneumoniae, and influenza virus. Taken together, these results suggest that PCPP may be a promising candidate for mucosal adjuvant to elicit protective immunity against respiratory infectious diseases.
Shim
Doo-Hee
DH
Mucosal Immunology Section, International Vaccine Institute, Seoul 151-818, Republic of Korea.
Ko
Hyun-Jeong
HJ
Volker
Gerdts
G
Potter
Andrew A
AA
Mutwiri
George
G
Babiuk
Lorne A
LA
Kweon
Mi-Na
MN
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis / Q000097:blood; D000914:Antibodies, Viral / Q000032:analysis / Q000097:blood; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016207:Cytokines / Q000032:analysis; D005260:Female; D007070:Immunoglobulin A / Q000032:analysis / Q000097:blood; D007074:Immunoglobulin G / Q000032:analysis / Q000097:blood; D007252:Influenza Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009092:Mucous Membrane / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000517:prevention & control; D010567:Pertussis Vaccine / Q000276:immunology*; D010666:Phenylpropionates / Q000008:administration & dosage*; D022242:Pneumococcal Vaccines / Q000276:immunology*; D011018:Pneumonia, Pneumococcal / Q000517:prevention & control; D011108:Polymers / Q000008:administration & dosage*; D012141:Respiratory Tract Infections / Q000517:prevention & control*; D016896:Treatment Outcome; D014917:Whooping Cough / Q000517:prevention & control
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000914:Antibodies, Viral; D016207:Cytokines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D010567:Pertussis Vaccine; D010666:Phenylpropionates; D022242:Pneumococcal Vaccines; D011108:Polymers; C508285:poly(bis(carboxylatoethylphenoxy)phosphazene)