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Objective: A phosphorylcholine (PC)-derivative with high binding ability (PCDB) was intranasally administered to mice with ovalbumin (OVA), and immune responses were investigated to determine whether PCDB has antigenicity and adjuvanticity., Methods: BALB/c mice were intranasally immunized with PCDB coupled with OVA, unbound PCDB plus OVA, cholera toxin (CT) plus OVA, OVA alone, and PCDB alone. Then, the production of OVA- and PC-specific antibodies in external secretions and serum, and the secretion of cytokines such as IL-4 and IFN-γ from splenic mononuclear cells by stimulation with PCDB and OVA were examined. Furthermore, the secretion of IL-12p40 from CD11c + cells following stimulation with PCDB was observed to clarify the adjuvant effect of PCDB through TLR4., Results: Intranasal immunization with PCDB plus OVA increased OVA- and PC-specific IgA in external secretions and OVA- and PC-specific antibodies in the serum. The analysis of IgG subclasses specific to OVA and PC showed a higher production of IgG1 than IgG2, and the secretion of both IL-4 and IFN-γ was enhanced. However, IL-12p40 secretion from CD11c + cells was increased and OVA-specific IgE production was not promoted by PCDB stimulation., Conclusion: Intranasal administration of the protein antigen with PCDB enhanced immune responses specific to the mixed antigen and PC. Although PCDB acted to bias the immune response toward the Th2-type, antigen-specific IgE production did not increase. These findings suggest that PCDB has the potential to be a mucosal vaccine with both adjuvanticity and antigenicity without causing side effects due to type I allergy., (Copyright © 2023. Published by Elsevier B.V.)

Phosphorylcholine (PC) is a structural component of a wide variety of pathogens including Streptococcus pneumoniae and Haemophilus influenzae, and anti-PC immune responses are known to protect mice against invasive bacterial diseases. The present study tested the capability of PC as an intranasal plurispecific vaccine against upper airway infections. BALB/c mice immunized with intranasal PC-keyhole limpet hemocyanin (KLH) plus cholera toxin (CT) as a mucosal adjuvant showed increased PC-specific IgM in serum, IgA in nasal wash and saliva, and numbers of PC-specific nasal and splenic antibody producing cells. Enhanced production of IL-4 and IFN-gamma by CD4+ T cells indicated the participation of Th2- and Th1-type cells. Salivary IgA antibodies produced by intranasal immunization with PC-KLH plus CT reacted to most strains of S. pneumoniae and H. influenzae. Further we demonstrated that the clearance of S. pneumoniae and H. influenzae from the nasal tract was significantly enhanced by nasal immunization with PC-KLH and CT. Thus, intranasal vaccination to induce PC-specific immune responses might help to prevent upper airway infections caused by S. pneumoniae and H. influenzae.

We aimed to investigate the inhibitory effect of 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer on the adherence of Streptococcus pneumoniae (Spn) and nontypeable Haemophilus influenzae (NTHi) in vitro and in vivo. Phosphorylcholine (PC) expression of 21 strains each of Spn and NTHi was evaluated using fluorescence-activated cell sorting; the adherence of bacteria to Detroit 562 cells and to the nasal mucosa of BALB/c mice was determined. MPC polymer-mediated inhibitory effects were compared with PC-keyhole limpet hemocyanin (PC-KLH)-mediated inhibitory effects. In vitro experiments showed that pretreatment with MPC polymer markedly inhibited the adherence of Spn and NTHi in a concentration dose–dependent manner independently of PC expression. No correlation was observed between PC expression and MPC polymer-mediated inhibitory effects. Contrarily, there was a significant negative correlation between PC-KLH-mediated inhibitory effects and PC expression in Spn and NTHi. The same results were obtained via in vivo experiments. The MPC polymer did not affect the histology of the nasal mucosa. MPC polymer might be effective to reduce the occurrence of upper respiratory tract infection caused by Spn and NTHi and could be applied for the development of local treatments, such as topical gargles and nebulizer medications. [ABSTRACT FROM AUTHOR]