title: Intramuscular immunization with poliovirus replicons primes for a humoral and cellular immune response to soluble antigen.
abstract: Vaccines that stimulate both cellular and humoral immunity will probably be needed to control many infectious diseases. Previously, our laboratory generated a vaccine vector that uses poliovirus genomes (replicons) in which the capsid genes have been replaced by foreign proteins. In the current study, we have evaluated the immune responses induced by immunization using poliovirus replicons encoding green fluorescent protein (GFP). Although intramuscular administration of replicons resulted in GFP expression in the muscle, the levels of anti-GFP antibodies in serum were low compared to those of mice immunized with soluble, recombinant GFP (rGFP). Intramuscular booster immunization with rGFP in animals primed with replicons encoding GFP resulted in production of both serum IgG1 and IgG2a GFP-specific antibodies. The cells isolated from spleens of animals primed with replicons and boosted with rGFP secreted IFN-gamma after in vitro stimulation with rGFP. Intramuscular immunization of animals with a single dose of replicons encoding GFP followed by two intranasal applications of rGFP resulted in serum GFP-specific IgG1 and IgG2a isotypes, consistent with induction of both humoral and cellular responses. The results of this study establish that immunization with replicons followed by boost with soluble antigen, even at a different site, can generate a more diverse immune response compared with immunization regimen using soluble antigen alone. This strategy could be exploited for the development of new vaccine approaches against infectious diseases.
authors.affiliation: The Department of Microbiology, Research University of Alabama at Birmingham, Birmingham, Alabama 35294-0024, USA.
authors.forename: Miroslav J
authors.initials: MJ
authors.lastname: Novak
authors.forename: Zina
authors.initials: Z
authors.lastname: Moldoveanu
authors.forename: Wen Qiang
authors.initials: WQ
authors.lastname: Huang
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Jackson
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Palmer
authors.forename: Sylvia A
authors.initials: SA
authors.lastname: McPherson
authors.forename: Casey D
authors.initials: CD
authors.lastname: Morrow
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000941:Antigens / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology; D005822:Genetic Vectors / Q000008:administration & dosage / Q000276:immunology; D049452:Green Fluorescent Proteins; D006801:Humans; D007114:Immunization; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000097:blood; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000096:biosynthesis; D008164:Luminescent Proteins / Q000235:genetics / Q000276:immunology*; D008565:Membrane Proteins; D051379:Mice; D008822:Mice, Transgenic; D017955:Poliovirus / Q000235:genetics / Q000276:immunology*; D011991:Receptors, Virus / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D012093:Replicon / Q000235:genetics / Q000276:immunology*; D012995:Solubility; D013154:Spleen / Q000166:cytology / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D000941:Antigens; D036022:Capsid Proteins; D007074:Immunoglobulin G; D008164:Luminescent Proteins; D008565:Membrane Proteins; D011991:Receptors, Virus; D011994:Recombinant Proteins; C442540:VP1 protein, Poliovirus; C066100:poliovirus receptor; D049452:Green Fluorescent Proteins; D007371:Interferon-gamma