title: Vaccination with heat-killed leishmania antigen or recombinant leishmanial protein and CpG oligodeoxynucleotides induces long-term memory CD4+ and CD8+ T cell responses and protection against leishmania major infection.
abstract: CpG oligodeoxynucleotides (ODN) have potent effects on innate and adaptive cellular immune responses. In this report, the ability of CpG ODN to confer long-term immunity and protection when used as a vaccine adjuvant with a clinical grade of leishmanial antigen, autoclaved Leishmania major (ALM), or a recombinant leishmanial protein was studied. In two different mouse models of L. major infection, vaccination with ALM plus CpG ODN was able to control infection and markedly reduce lesion development in susceptible BALB/c and resistant C57BL/6 (B6) mice, respectively, up to 12 wk after immunization. Moreover, B6 mice immunized with ALM plus CpG ODNs were still protected against infectious challenge even 6 mo after vaccination. In terms of immune correlates of protection, ALM plus CpG ODN-vaccinated mice displayed L. major-specific T helper cell 1 and CD8+ responses. In addition, complete protection was markedly abrogated in mice depleted of CD8+ T cells at the time of vaccination. Similarly, mice vaccinated with a recombinant leishmanial protein plus CpG ODN also had long-term protection that was dependent on CD8+ T cells in vivo. Together, these data demonstrate that CpG ODN, when used as a vaccine adjuvant with either a recombinant protein or heat-killed leishmanial antigen, can induce long-term protection against an intracellular infection in a CD8-dependent manner.
authors.affiliation: Cellular Immunology Section, Vaccine Research Center, Bethesda, MD 20892, USA.
authors.forename: Elizabeth G
authors.initials: EG
authors.lastname: Rhee
authors.forename: Susana
authors.initials: S
authors.lastname: Mendez
authors.forename: Javeed A
authors.initials: JA
authors.lastname: Shah
authors.forename: Chang-you
authors.initials: CY
authors.lastname: Wu
authors.forename: Joanna R
authors.initials: JR
authors.lastname: Kirman
authors.forename: Tara N
authors.initials: TN
authors.lastname: Turon
authors.forename: Dylan F
authors.initials: DF
authors.lastname: Davey
authors.forename: Heather
authors.initials: H
authors.lastname: Davis
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Klinman
authors.forename: Rhea N
authors.initials: RN
authors.lastname: Coler
authors.forename: David L
authors.initials: DL
authors.lastname: Sacks
authors.forename: Robert A
authors.initials: RA
authors.lastname: Seder
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000008:administration & dosage*; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018899:CpG Islands; D005260:Female; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D018320:Leishmania major / Q000276:immunology*; D007896:Leishmaniasis / Q000517:prevention & control*; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage; D015800:Protozoan Proteins / Q000008:administration & dosage*; D016052:Protozoan Vaccines / Q000008:administration & dosage*; D011994:Recombinant Proteins / Q000008:administration & dosage
chemical_list: D000953:Antigens, Protozoan; D009838:Oligodeoxyribonucleotides; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D011994:Recombinant Proteins; D007371:Interferon-gamma