| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
CUTTING EDGE |
,
,§
*
Loeb Research Institute, Ottawa, Canada;
Departments of Cellular and Molecular Medicine and
Microbiology, Immunology, and Biochemistry, Faculty of Medicine, and
§
School of Rehabilitation Sciences, Faculty of Health Sciences, University of Ottawa, Ottawa, Canada
Mucosal immunity is difficult to induce with subunit vaccines unless such vaccines are administered with a mucosal adjuvant such as cholera toxin (CT); however, CT is toxic in humans. Synthetic oligodeoxynucleotides containing immunostimulatory CpG motifs (CpG) are potent adjuvants for the induction of Th1-like systemic immune responses against parenterally delivered proteins. Here, we show in mice that intranasal delivery of hepatitis B surface Ag, which alone has no effect, elicits good immune responses when given with CpG oligodeoxynucleotides and/or CT. Overall, CpG is superior to CT for the induction of humoral and cell-mediated systemic immunity as well as mucosal immune responses (IgA) at local (lung) and distant (feces) sites. Furthermore, CpG and CT act synergistically, giving stronger responses than those observed with 10 times more of either adjuvant alone. Ab isotypes were predominantly IgG1 (Th2-like) with CT, mixed IgG1/IgG2a (Th0) with CpG, and predominantly IgG2a (Th1-like) with CpG and CT together.
This article has been cited by other articles:
|
|
 |
|
  E. Meoni, E. Faenzi, E. Frigimelica, L. Zedda, D. Skibinski, S. Giovinazzi, A. Bonci, R. Petracca, E. Bartolini, G. Galli, et al. CT043, a Protective Antigen That Induces a CD4+ Th1 Response during Chlamydia trachomatis Infection in Mice and Humans Infect. Immun., September 1, 2009; 77(9): 4168 - 4176. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Klinman, H. Shirota, D. Tross, T. Sato, and S. Klaschik Synthetic oligonucleotides as modulators of inflammation J. Leukoc. Biol., October 1, 2008; 84(4): 958 - 964. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. W. Mapletoft, M. Oumouna, J. Kovacs-Nolan, L. Latimer, G. Mutwiri, L. A. Babiuk, and S. van Drunen Littel-van den Hurk Intranasal immunization of mice with a formalin-inactivated bovine respiratory syncytial virus vaccine co-formulated with CpG oligodeoxynucleotides and polyphosphazenes results in enhanced protection J. Gen. Virol., January 1, 2008; 89(1): 250 - 260. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Adamsson, M. Lindblad, A. Lundqvist, D. Kelly, J. Holmgren, and A. M. Harandi Novel immunostimulatory agent based on CpG oligodeoxynucleotide linked to the nontoxic B subunit of cholera toxin. J. Immunol., April 15, 2006; 176(8): 4902 - 4913. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Q. Jiang, A. Patrick, R. B. Moss, and K. L. Rosenthal CD8+ T-Cell-Mediated Cross-Clade Protection in the Genital Tract following Intranasal Immunization with Inactivated Human Immunodeficiency Virus Antigen Plus CpG Oligodeoxynucleotides J. Virol., January 1, 2005; 79(1): 393 - 400. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. F. Pinto, R. O. Pinheiro, A. Rayol, V. Larraga, and B. Rossi-Bergmann Intranasal Vaccination against Cutaneous Leishmaniasis with a Particulated Leishmanial Antigen or DNA Encoding LACK Infect. Immun., August 1, 2004; 72(8): 4521 - 4527. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-i. Ito, K. J. Ishii, H. Shirota, and D. M. Klinman CpG Oligodeoxynucleotides Improve the Survival of Pregnant and Fetal Mice following Listeria monocytogenes Infection Infect. Immun., June 1, 2004; 72(6): 3543 - 3548. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. H. Bashir, S. Louie, H. N. Shi, and C. Nagler-Anderson Toll-Like Receptor 4 Signaling by Intestinal Microbes Influences Susceptibility to Food Allergy J. Immunol., June 1, 2004; 172(11): 6978 - 6987. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Coban, K. J. Ishii, A. W. Stowers, D. B. Keister, D. M. Klinman, and N. Kumar Effect of CpG Oligodeoxynucleotides on the Immunogenicity of Pfs25, a Plasmodium falciparum Transmission-Blocking Vaccine Antigen Infect. Immun., January 1, 2004; 72(1): 584 - 588. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. A. Prince, J. J. Mond, D. D. Porter, K. C. Yim, S. J. Lan, and D. M. Klinman Immunoprotective Activity and Safety of a Respiratory Syncytial Virus Vaccine: Mucosal Delivery of Fusion Glycoprotein with a CpG Oligodeoxynucleotide Adjuvant J. Virol., December 15, 2003; 77(24): 13156 - 13160. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. N. Boyaka, A. Tafaro, R. Fischer, S. H. Leppla, K. Fujihashi, and J. R. McGhee Effective Mucosal Immunity to Anthrax: Neutralizing Antibodies and Th Cell Responses Following Nasal Immunization with Protective Antigen J. Immunol., June 1, 2003; 170(11): 5636 - 5643. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-M. Kang and R. W. Compans Enhancement of Mucosal Immunization with Virus-Like Particles of Simian Immunodeficiency Virus J. Virol., March 15, 2003; 77(6): 3615 - 3623. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Jiang, H. J. Baker, and B. F. Smith Mucosal Immunization with Helicobacter, CpG DNA, and Cholera Toxin Is Protective Infect. Immun., January 1, 2003; 71(1): 40 - 46. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. FATTORINI, R. CRETI, R. NISINI, R. PIETROBONO, Y. FAN, A. STRINGARO, G. ARANCIA, O. SERLUPI-CRESCENZI, E. IONA, and G. OREFICI Recombinant GroES in combination with CpG oligodeoxynucleotides protects mice against Mycobacterium avium infection J. Med. Microbiol., December 1, 2002; 51(12): 1071 - 1079. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. He, A. Mitchell, T. Morcol, and S. J. D. Bell Calcium Phosphate Nanoparticles Induce Mucosal Immunity and Protection against Herpes Simplex Virus Type 2 Clin. Vaccine Immunol., September 1, 2002; 9(5): 1021 - 1024. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. P. Juffermans, J. C. Leemans, S. Florquin, A. Verbon, A. H. Kolk, P. Speelman, S. J. H. van Deventer, and T. van der Poll CpG Oligodeoxynucleotides Enhance Host Defense during Murine Tuberculosis Infect. Immun., January 1, 2002; 70(1): 147 - 152. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Horner, S. K. Datta, K. Takabayashi, I. M. Belyakov, T. Hayashi, N. Cinman, M.-D. Nguyen, J. H. Van Uden, J. A. Berzofsky, D. D. Richman, et al. Immunostimulatory DNA-Based Vaccines Elicit Multifaceted Immune Responses Against HIV at Systemic and Mucosal Sites J. Immunol., August 1, 2001; 167(3): 1584 - 1591. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Shirota, K. Sano, N. Hirasawa, T. Terui, K. Ohuchi, T. Hattori, K. Shirato, and G. Tamura Novel Roles of CpG Oligodeoxynucleotides as a Leader for the Sampling and Presentation of CpG-Tagged Antigen by Dendritic Cells J. Immunol., July 1, 2001; 167(1): 66 - 74. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. S. Gallichan, R. N. Woolstencroft, T. Guarasci, M. J. McCluskie, H. L. Davis, and K. L. Rosenthal Intranasal Immunization with CpG Oligodeoxynucleotides as an Adjuvant Dramatically Increases IgA and Protection Against Herpes Simplex Virus-2 in the Genital Tract J. Immunol., March 1, 2001; 166(5): 3451 - 3457. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Peng, H. Wang, X. Mao, K. T. HayGlass, and F. E. R. Simons CpG oligodeoxynucleotide vaccination suppresses IgE induction but may fail to down-regulate ongoing IgE responses in mice Int. Immunol., January 1, 2001; 13(1): 3 - 11. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. N. Shi, H. Y. Liu, and C. Nagler-Anderson Enteric Infection Acts as an Adjuvant for the Response to a Model Food Antigen J. Immunol., December 1, 2000; 165(11): 6174 - 6182. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Meyer, K. T. Wilson, and S. P. James Modulation of Innate Cytokine Responses by Products of Helicobacter pylori Infect. Immun., November 1, 2000; 68(11): 6265 - 6272. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Olszewska, C. D. Partidos, and M. W. Steward Antipeptide Antibody Responses following Intranasal Immunization: Effectiveness of Mucosal Adjuvants Infect. Immun., September 1, 2000; 68(9): 4923 - 4929. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. L. Freidag, G. B. Melton, F. Collins, D. M. Klinman, A. Cheever, L. Stobie, W. Suen, and R. A. Seder CpG Oligodeoxynucleotides and Interleukin-12 Improve the Efficacy of Mycobacterium bovis BCG Vaccination in Mice Challenged with M. tuberculosis Infect. Immun., May 1, 2000; 68(5): 2948 - 2953. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Shirota, K. Sano, T. Kikuchi, G. Tamura, and K. Shirato Regulation of T-helper Type 2 Cell and Airway Eosinophilia by Transmucosal Coadministration of Antigen and Oligodeoxynucleotides Containing CpG Motifs Am. J. Respir. Cell Mol. Biol., February 1, 2000; 22(2): 176 - 182. [Abstract] [Full Text]
|
|
|
|
|
|
D. M. Klinman, J. Conover, and C. Coban Repeated Administration of Synthetic Oligodeoxynucleotides Expressing CpG Motifs Provides Long-Term Protection against Bacterial Infection Infect. Immun., November 1, 1999; 67(11): 5658 - 5663. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Wild, M. J. Grusby, R. Schirmbeck, and J. Reimann Priming MHC-I-Restricted Cytotoxic T Lymphocyte Responses to Exogenous Hepatitis B Surface Antigen Is CD4+ T Cell Dependent J. Immunol., August 15, 1999; 163(4): 1880 - 1887. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Schirmbeck, K. Melber, and J. Reimann Adjuvants that enhance priming of cytotoxic T cells to a Kb-restricted epitope processed from exogenous but not endogenous hepatitis B surface antigen Int. Immunol., July 1, 1999; 11(7): 1093 - 1102. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. B. Millan, R. Weeratna, A. M. Krieg, C.-A. Siegrist, and H. L. Davis CpG DNA can induce strong Th1 humoral and cell-mediated immune responses against hepatitis B surface antigen in young mice PNAS, December 22, 1998; 95(26): 15553 - 15558. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
