| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Molecular Immunogenetics and Vaccine Research Section, Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;
Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112; and
Mucosal Immunity Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
We examined the interplay between cytokines and adjuvants to optimize the induction of CTL by a mucosal HIV peptide vaccine. We show synergy between IL-12 and GM-CSF when administered together with the HIV peptide PCLUS3–18IIIB and cholera toxin (CT) in the induction of CTL activity and protection against mucosal viral transmission. Further, we examine the efficacy of mutant Escherichia coli labile toxin, LT(R192G), as a less toxic adjuvant than CT. LT(R192G) was as effective as or more effective than CT at inducing a mucosal CTL response. Moreover, LT(R192G) was as effective without IL-12 as CT was when combined with IL-12, and the response elicited by LT(R192G) with the vaccine was not further enhanced by the addition of IL-12. GM-CSF synergized with LT(R192G) without exogenous IL-12. Therefore, LT(R192G) may induce a more favorable cytokine response by not inhibiting IL-12 production. In particular, less IL-4 is made after LT(R192G) than CT immunization, and the response is less susceptible to anti-IL-12 inhibition. Thus, the choice of mucosal adjuvant affects the cytokine environment, and the mucosal response and protection can be enhanced by manipulating the cytokine environment with synergistic cytokine combinations incorporated in the vaccine.
This article has been cited by other articles:
|
|
 |
|
  K. Yang, B. J. Whalen, R. S. Tirabassi, L. K. Selin, T. S. Levchenko, V. P. Torchilin, E. H. Kislauskis, and D. L. Guberski A DNA Vaccine Prime Followed by a Liposome-Encapsulated Protein Boost Confers Enhanced Mucosal Immune Responses and Protection J. Immunol., May 1, 2008; 180(9): 6159 - 6167. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. M. Belyakov, S. Kozlowski, M. Mage, J. D. Ahlers, L. F. Boyd, D. H. Margulies, and J. A. Berzofsky Role of {alpha}3 domain of class I MHC molecules in the activation of high- and low-avidity CD8+ CTLs Int. Immunol., December 1, 2007; 19(12): 1413 - 1420. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. M. Belyakov, D. Isakov, Q. Zhu, A. Dzutsev, and J. A. Berzofsky A Novel Functional CTL Avidity/Activity Compartmentalization to the Site of Mucosal Immunization Contributes to Protection of Macaques against Simian/Human Immunodeficiency Viral Depletion of Mucosal CD4+ T Cells J. Immunol., June 1, 2007; 178(11): 7211 - 7221. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. M. Belyakov, D. Isakov, Q. Zhu, A. Dzutsev, D. Klinman, and J. A. Berzofsky Enhancement of CD8+ T Cell Immunity in the Lung by CpG Oligodeoxynucleotides Increases Protective Efficacy of a Modified Vaccinia Ankara Vaccine against Lethal Poxvirus Infection Even in a CD4-Deficient Host J. Immunol., November 1, 2006; 177(9): 6336 - 6343. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. M. Belyakov, V. A. Kuznetsov, B. Kelsall, D. Klinman, M. Moniuszko, M. Lemon, P. D. Markham, R. Pal, J. D. Clements, M. G. Lewis, et al. Impact of vaccine-induced mucosal high-avidity CD8+CTLs in delay of AIDS viral dissemination from mucosa Blood, April 15, 2006; 107(8): 3258 - 3264. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Hajishengallis, S. Arce, C.M. Gockel, T.D. Connell, and M.W. Russell Immunomodulation with Enterotoxins for the Generation of Secretory Immunity or Tolerance: Applications for Oral Infections J. Dent. Res., December 1, 2005; 84(12): 1104 - 1116. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Glynn, C. J. Roy, B. S. Powell, J. J. Adamovicz, L. C. Freytag, and J. D. Clements Protection against Aerosolized Yersinia pestis Challenge following Homologous and Heterologous Prime-Boost with Recombinant Plague Antigens Infect. Immun., August 1, 2005; 73(8): 5256 - 5261. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Zhang, R. Fayad, X. Wang, D. Quinn, and L. Qiao Human Immunodeficiency Virus Type 1 Gag-Specific Mucosal Immunity after Oral Immunization with Papillomavirus Pseudoviruses Encoding Gag J. Virol., October 1, 2004; 78(19): 10249 - 10257. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Stevens, K. E. Howard, S. Nordone, M. Burkhard, and G. A. Dean Oral Immunization with Recombinant Listeria monocytogenes Controls Virus Load after Vaginal Challenge with Feline Immunodeficiency Virus J. Virol., August 1, 2004; 78(15): 8210 - 8218. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Garulli, Y. Kawaoka, and M. R. Castrucci Mucosal and Systemic Immune Responses to a Human Immunodeficiency Virus Type 1 Epitope Induced upon Vaginal Infection with a Recombinant Influenza A Virus J. Virol., January 15, 2004; 78(2): 1020 - 1025. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. U. Vogel, M. R. Reynolds, D. H. Fuller, K. Vielhuber, T. Shipley, J. T. Fuller, K. J. Kunstman, G. Sutter, M. L. Marthas, V. Erfle, et al. Multispecific Vaccine-Induced Mucosal Cytotoxic T Lymphocytes Reduce Acute-Phase Viral Replication but Fail in Long-Term Control of Simian Immunodeficiency Virus SIVmac239 J. Virol., December 15, 2003; 77(24): 13348 - 13360. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Daftarian, S. Ali, R. Sharan, S. F. Lacey, C. La Rosa, J. Longmate, C. Buck, R. F. Siliciano, and D. J. Diamond Immunization with Th-CTL Fusion Peptide and Cytosine-Phosphate-Guanine DNA in Transgenic HLA-A2 Mice Induces Recognition of HIV-Infected T Cells and Clears Vaccinia Virus Challenge J. Immunol., October 15, 2003; 171(8): 4028 - 4039. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. M. Belyakov, P. Earl, A. Dzutsev, V. A. Kuznetsov, M. Lemon, L. S. Wyatt, J. T. Snyder, J. D. Ahlers, G. Franchini, B. Moss, et al. Shared modes of protection against poxvirus infection by attenuated and conventional smallpox vaccine viruses PNAS, August 5, 2003; 100(16): 9458 - 9463. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. N. Boyaka, M. Ohmura, K. Fujihashi, T. Koga, M. Yamamoto, M.-N. Kweon, Y. Takeda, R. J. Jackson, H. Kiyono, Y. Yuki, et al. Chimeras of Labile Toxin One and Cholera Toxin Retain Mucosal Adjuvanticity and Direct Th Cell Subsets Via Their B Subunit J. Immunol., January 1, 2003; 170(1): 454 - 462. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Ahlers, I. M. Belyakov, M. Terabe, R. Koka, D. D. Donaldson, E. K. Thomas, and J. A. Berzofsky A push-pull approach to maximize vaccine efficacy: Abrogating suppression with an IL-13 inhibitor while augmenting help with granulocyte/macrophage colony-stimulating factor and CD40L PNAS, October 1, 2002; 99(20): 13020 - 13025. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. P. Bradney, G. D. Sempowski, H.-X. Liao, B. F. Haynes, and H. F. Staats Cytokines as Adjuvants for the Induction of Anti-Human Immunodeficiency Virus Peptide Immunoglobulin G (IgG) and IgA Antibodies in Serum and Mucosal Secretions after Nasal Immunization J. Virol., January 15, 2002; 76(2): 517 - 524. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Bukreyev, I. M. Belyakov, J. A. Berzofsky, B. R. Murphy, and P. L. Collins Granulocyte-Macrophage Colony-Stimulating Factor Expressed by Recombinant Respiratory Syncytial Virus Attenuates Viral Replication and Increases the Level of Pulmonary Antigen-Presenting Cells J. Virol., December 15, 2001; 75(24): 12128 - 12140. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Ahlers, I. M. Belyakov, S. Matsui, and J. A. Berzofsky Signals delivered through TCR instruct IL-12 receptor (IL-12R) expression: IL-12 and tumor necrosis factor-{alpha} synergize for IL-12R expression at low antigen dose Int. Immunol., November 1, 2001; 13(11): 1433 - 1442. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. F. Staats, C. P. Bradney, W. M. Gwinn, S. S. Jackson, G. D. Sempowski, H.-X. Liao, N. L. Letvin, and B. F. Haynes Cytokine Requirements for Induction of Systemic and Mucosal CTL After Nasal Immunization J. Immunol., November 1, 2001; 167(9): 5386 - 5394. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Ahlers, I. M. Belyakov, S. Matsui, and J. A. Berzofsky Mechanisms of cytokine synergy essential for vaccine protection against viral challenge Int. Immunol., July 1, 2001; 13(7): 897 - 908. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
