title: Novel mucosal vaccines generated by genetic conjugation of heterologous proteins to pneumolysin (PLY) from Streptococcus pneumoniae.
abstract: Induction of immunity at mucosal surfaces is thought to be an essential feature in the protection of the host against the many pathogens that gain access through these surfaces. Here we describe how strong local and systemic immune responses can be generated when proteins are genetically conjugated to pneumolysin (PLY) from Streptococcus pneumoniae. Using green fluorescent protein (eGFP) and PsaA from S. pneumoniae, we have shown that genetic fusion (eGFPPLY and PsaAPLY) is essential to ensure high levels of antigen specific IgG and IgA in the serum and at mucosal surfaces. This form of vaccination is highly effective with antigen specific antibodies detected after a single dose of nanogram quantities of the conjugated proteins. In addition, generation of a non-toxic variant (eGFPDelta6PLY) indicated that while the toxic activity of PLY was not essential for adjuvanticity, it contributed to the magnitude of the response generated. Whilst vaccination with the PsaAPLY fusion proteins did not protect the animals from challenge, these studies confirm the utility of pneumolysin to act as a novel mucosal adjuvant to substantially increase the local and systemic humoral response to genetically fused protein antigens.
authors.affiliation: Division of Infection and Immunity, Faculty of Biomedical and Life Sciences, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow G12 8TA, UK.
authors.forename: Gill
authors.initials: G
authors.lastname: Douce
authors.forename: Kirsty
authors.initials: K
authors.lastname: Ross
authors.forename: Graeme
authors.initials: G
authors.lastname: Cowan
authors.forename: Jiangtao
authors.initials: J
authors.lastname: Ma
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Mitchell
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000235:genetics / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000906:Antibodies / Q000097:blood; D001426:Bacterial Proteins / Q000235:genetics / Q000494:pharmacology / Q000633:toxicity; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000276:immunology; D006801:Humans; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000032:analysis / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008074:Lipoproteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011506:Proteins / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D017384:Sequence Deletion; D013301:Streptolysins / Q000235:genetics / Q000494:pharmacology* / Q000633:toxicity; D014612:Vaccines / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology
chemical_list: D018829:Adhesins, Bacterial; D000276:Adjuvants, Immunologic; D000906:Antibodies; D001426:Bacterial Proteins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008074:Lipoproteins; D011506:Proteins; C085000:PsaA protein, Streptococcus; D011993:Recombinant Fusion Proteins; D013301:Streptolysins; D014612:Vaccines; D014614:Vaccines, Synthetic; C485184:enhanced green fluorescent protein; C032290:plY protein, Streptococcus pneumoniae; D049452:Green Fluorescent Proteins