title: Priming characteristics of peptide mimotopes of carbohydrate antigens.
abstract: Immunization with peptide mimetics of carbohydrate antigens can induce functional carbohydrate-reactive antibodies. Here, we examine the immune characteristics of alternative approaches in prime and boost strategies using glycosylated HIV-1 envelope protein and model tumor associated carbohydrate antigens. Our results indicate that peptide mimotopes either in a DNA or carrier-conjugated format can induce comparable levels of IgM and IgG. Carbohydrate boosting of peptide-primed animals does not affect end-point titer, however, boosting mediates a stable long lasting carbohydrate reactive IgM response, not achievable by carbohydrate immunization alone. Boosting with carbohydrate in animals primed with DNA- or peptide-conjugate, facilitates the induction of detectable IgG with a dominant IgG2a isotype. Immunization with HIV-1 envelope glycoprotein of peptide-primed animals induces different IgG isotype profiles with a dominant IgG1 antibody. We observed that HIV-1 envelope glycoprotein immunization of peptide primed mice induces a cross-reactive cellular response, as detected by cytokine secretion, which lends to IFN-gamma production upon splenocyte stimulation and CTL activity against recombinant vaccinia virus infected cells after in vitro stimulation. DNA immunization with mimotope, inclusion of a T-cell epitope from the HIV-1 envelope protein in the expression cassette and co-administration with IL-12 or GM-CSF encoding plasmids activate a cellular response to the HIV-1 envelope protein.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Behjatolah
authors.initials: B
authors.lastname: Monzavi-Karbassi
authors.forename: Shahram
authors.initials: S
authors.lastname: Shamloo
authors.forename: Matthew
authors.initials: M
authors.lastname: Kieber-Emmons
authors.forename: Fariba
authors.initials: F
authors.lastname: Jousheghany
authors.forename: Ping
authors.initials: P
authors.lastname: Luo
authors.forename: Kaity Y
authors.initials: KY
authors.lastname: Lin
authors.forename: Gina
authors.initials: G
authors.lastname: Cunto-Amesty
authors.forename: David B
authors.initials: DB
authors.lastname: Weiner
authors.forename: Thomas
authors.initials: T
authors.lastname: Kieber-Emmons
mesh_terms: D000818:Animals; D000917:Antibody Formation; D016466:CHO Cells; D002241:Carbohydrates / Q000737:chemistry* / Q000276:immunology; D006224:Cricetinae; D003429:Cross Reactions; D018984:Epitopes, T-Lymphocyte / Q000235:genetics; D006031:Glycosylation; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology*; D007074:Immunoglobulin G / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D066298:In Vitro Techniques; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D018716:Molecular Mimicry; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology
chemical_list: D002241:Carbohydrates; D018984:Epitopes, T-Lymphocyte; D015699:HIV Envelope Protein gp120; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D010455:Peptides; D019444:Vaccines, DNA; D007371:Interferon-gamma