title: Intranasal vaccination with the recombinant Listeria monocytogenes ΔactA prfA* mutant elicits robust systemic and pulmonary cellular responses and secretory mucosal IgA.
abstract: We previously showed that recombinant (r) Listeria monocytogenes carrying ΔactA and a selected prfA* mutation (r-Listeria ΔactA prfA*) secreted >100-fold more immunogen in broth culture than wild-type r-Listeria or r-Listeria ΔactA and elicited much greater cellular and humoral immune responses than r-Listeria ΔactA after intravenous vaccination of mice. Here, we conducted comparative studies evaluating vaccine-elicited immune responses in systemic and mucosal sites after intranasal, intravenous, intraperitoneal, or subcutaneous immunization of mice with r-Listeria ΔactA prfA* vaccine candidates. Intranasal vaccination of mice with r-Listeria ΔactA prfA* vaccine candidates elicited a robust gamma interferon-positive (IFN-γ(+)) cellular response in systemic sites, although intravenous or intraperitoneal immunization was more efficient. Surprisingly, intranasal vaccination elicited an appreciable pulmonary IFN-γ(+) cellular response that was nonstatistically higher than the magnitude induced by the intravenous route but was significantly greater than that elicited by subcutaneous immunization. Furthermore, although intranasal r-Listeria ΔactA prfA* delivery induced poor systemic IgG responses, intranasal vaccination elicited appreciable secretory immunogen-specific IgA titers that were similar to or higher in mucosal fluid than those induced by subcutaneous and intravenous immunizations. Thus, intranasal vaccination with r-Listeria ΔactA prfA* appears to be a useful approach for eliciting robust systemic and pulmonary cellular responses and measurable secretory mucosal IgA titers.
authors.affiliation: Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago, Illinois 60612, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Qiu
authors.forename: Lin
authors.initials: L
authors.lastname: Yan
authors.forename: Jianbo
authors.initials: J
authors.lastname: Chen
authors.forename: Crystal Y
authors.initials: CY
authors.lastname: Chen
authors.forename: Ling
authors.initials: L
authors.lastname: Shen
authors.forename: Norman L
authors.initials: NL
authors.lastname: Letvin
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
authors.forename: Nancy
authors.initials: N
authors.lastname: Freitag
authors.forename: Lijun
authors.initials: L
authors.lastname: Rong
authors.forename: James T
authors.initials: JT
authors.lastname: Frencher
authors.forename: Dan
authors.initials: D
authors.lastname: Huang
authors.forename: Xunming
authors.initials: X
authors.lastname: Wang
authors.forename: Zheng W
authors.initials: ZW
authors.lastname: Chen
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood*; D001426:Bacterial Proteins / Q000235:genetics; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D007071:Immunoglobulin A, Secretory / Q000032:analysis*; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008089:Listeria monocytogenes / Q000235:genetics / Q000276:immunology*; D008168:Lung / Q000276:immunology*; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D010454:Peptide Termination Factors / Q000235:genetics; D014611:Vaccination / Q000379:methods*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D007071:Immunoglobulin A, Secretory; D008565:Membrane Proteins; D010454:Peptide Termination Factors; C545356:PrfA protein, Listeria monocytogenes; D014613:Vaccines, Attenuated; C072980:actA protein, Listeria monocytogenes