HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gherardi, M. M. Articles by Esteban, M. Search for Related Content PubMed PubMed Citation Articles by Gherardi, M. M. Articles by Esteban, M.

IL-12 Delivery from Recombinant Vaccinia Virus Attenuates the Vector and Enhances the Cellular Immune Response Against HIV-1 Env in a Dose-Dependent Manner¹

M. Magdalena Gherardi^2,*, Juan C. Ramirez^2,*, Dolores Rodríguez^*, Juan R. Rodríguez^*, Gen-Ichiro Sano, Fidel Zavala and Mariano Esteban^3,*

^* Department of Molecular and Cellular Biology, Centro Nacional de Biotecnologia, Consejo Superior de Investigaciones Cientificas, Campus Universidad Autónoma, Madrid, Spain; and Department of Medical and Molecular Parasitology, New York University Medical Center, New York, NY 10010

To develop vaccination strategies against HIV-1 infection aimed to specifically enhance the cell-mediated immunity (CMI), we have engineered vaccinia virus (VV) recombinants expressing HIV-1 Env (rVVenv) and murine IL-12 (rVVlucIL-12) genes or coexpressing both genes (rVVenvIL-12). In mice inoculated with rVVlucIL-12 there is a rapid clearance of the virus, and this correlates with the induction of high levels of IL-12 and IFN- in serum and spleen early after infection. Enzyme-linked immunospot analysis of mice inoculated with rVVlucIL-12, revealed a nearly 2-fold increase in the number of specific anti-VV CD8⁺ T cells compared with that in mice given control rVV, and the serum Ab response was biased in favor of a Th1 response. An enhancement of about 2-fold in the number of anti-gp160 IFN--secreting CD8⁺ T cells was observed in mice inoculated with rVVenvIL-12, when a dose of 1 x 10⁷ PFU/mouse was used, but this enhancement was not observed when mice were given 5 x 10⁷ PFU. This variation with virus dosage was confirmed in mice immunized simultaneously with different multiplicities of rVV expressing singly the env or IL-12 genes. The highest specific CMI was obtained in mice coadministered a low dose (2 x 10⁴ PFU) of rVVlucIL-12 and 1 x 10⁷ PFU of rVVenv. Our findings provide evidence for specific enhancement of the CMI to HIV-1 Env by the differential expression of IL-12 and env genes delivered from VV recombinants. This approach can be of wide vaccination interest as a means to improve immune responses to other Ags.

This article has been cited by other articles:

				Y. Peng, F.-c. Lin, P. H. Verardi, L. A. Jones, M. B. McChesney, and T. D. Yilma Pseudotyped Single-Cycle Simian Immunodeficiency Viruses Expressing Gamma Interferon Augment T-Cell Priming Responses In Vitro J. Virol., March 1, 2007; 81(5): 2187 - 2195. [Abstract] [Full Text] [PDF]

				J. L. Najera, C. E. Gomez, E. Domingo-Gil, M. M. Gherardi, and M. Esteban Cellular and Biochemical Differences between Two Attenuated Poxvirus Vaccine Candidates (MVA and NYVAC) and Role of the C7L Gene. J. Virol., June 1, 2006; 80(12): 6033 - 6047. [Abstract] [Full Text] [PDF]

				M. M. Gherardi and M. Esteban Recombinant poxviruses as mucosal vaccine vectors J. Gen. Virol., November 1, 2005; 86(11): 2925 - 2936. [Abstract] [Full Text] [PDF]

				N. W. Bartlett, L. Dumoutier, J.-C. Renauld, S. V. Kotenko, C. E. McVey, H.-J. Lee, and G. L. Smith A new member of the interleukin 10-related cytokine family encoded by a poxvirus J. Gen. Virol., June 1, 2004; 85(6): 1401 - 1412. [Abstract] [Full Text] [PDF]

				M. M. Gherardi, E. Perez-Jimenez, J. L. Najera, and M. Esteban Induction of HIV Immunity in the Genital Tract After Intranasal Delivery of a MVA Vector: Enhanced Immunogenicity After DNA Prime-Modified Vaccinia Virus Ankara Boost Immunization Schedule J. Immunol., May 15, 2004; 172(10): 6209 - 6220. [Abstract] [Full Text] [PDF]

				F. A. Legrand, P. H. Verardi, L. A. Jones, K. S. Chan, Y. Peng, and T. D. Yilma Induction of Potent Humoral and Cell-Mediated Immune Responses by Attenuated Vaccinia Virus Vectors with Deleted Serpin Genes J. Virol., March 15, 2004; 78(6): 2770 - 2779. [Abstract] [Full Text] [PDF]

				H. Ozwara, J. A. M. Langermans, C. H. M. Kocken, A. van der Wel, P. H. van der Meide, R. A. W. Vervenne, J. M. Mwenda, and A. W. Thomas Transfected Plasmodium knowlesi Produces Bioactive Host Gamma Interferon: a New Perspective for Modulating Immune Responses to Malaria Parasites Infect. Immun., August 1, 2003; 71(8): 4375 - 4381. [Abstract] [Full Text] [PDF]

				M. M. Gherardi, J. C. Ramirez, and M. Esteban IL-12 and IL-18 act in synergy to clear vaccinia virus infection: involvement of innate and adaptive components of the immune system J. Gen. Virol., August 1, 2003; 84(8): 1961 - 1972. [Abstract] [Full Text] [PDF]

				M. M. Gherardi, J. L. Najera, E. Perez-Jimenez, S. Guerra, A. Garcia-Sastre, and M. Esteban Prime-Boost Immunization Schedules Based on Influenza Virus and Vaccinia Virus Vectors Potentiate Cellular Immune Responses against Human Immunodeficiency Virus Env Protein Systemically and in the Genitorectal Draining Lymph Nodes J. Virol., June 15, 2003; 77(12): 7048 - 7057. [Abstract] [Full Text] [PDF]

				C. Gonzalez-Lopez, J. Martinez-Costas, M. Esteban, and J. Benavente Evidence that avian reovirus {sigma}A protein is an inhibitor of the double-stranded RNA-dependent protein kinase J. Gen. Virol., June 1, 2003; 84(6): 1629 - 1639. [Abstract] [Full Text] [PDF]

				N. Garg and R. L. Tarleton Genetic Immunization Elicits Antigen-Specific Protective Immune Responses and Decreases Disease Severity in Trypanosoma cruzi Infection Infect. Immun., October 1, 2002; 70(10): 5547 - 5555. [Abstract] [Full Text] [PDF]

				A. A. Ansari, A. E. Mayne, J. B. Sundstrom, P. Bostik, B. Grimm, J. D. Altman, and F. Villinger Administration of Recombinant Rhesus Interleukin-12 during Acute Simian Immunodeficiency Virus (SIV) Infection Leads to Decreased Viral Loads Associated with Prolonged Survival in SIVmac251-Infected Rhesus Macaques J. Virol., February 15, 2002; 76(4): 1731 - 1743. [Abstract] [Full Text] [PDF]

				H.-W. Chen, C.-H. Pan, H.-W. Huan, M.-Y. Liau, J.-R. Chiang, and M.-H. Tao Suppression of Immune Response and Protective Immunity to a Japanese Encephalitis Virus DNA Vaccine by Coadministration of an IL-12-Expressing Plasmid J. Immunol., June 15, 2001; 166(12): 7419 - 7426. [Abstract] [Full Text] [PDF]

				J. C. Ramírez, M. M. Gherardi, D. Rodríguez, and M. Esteban Attenuated Modified Vaccinia Virus Ankara Can Be Used as an Immunizing Agent under Conditions of Preexisting Immunity to the Vector J. Virol., August 15, 2000; 74(16): 7651 - 7655. [Abstract] [Full Text]

				M. M. Gherardi, J. C. Ramírez, and M. Esteban Interleukin-12 (IL-12) Enhancement of the Cellular Immune Response against Human Immunodeficiency Virus Type 1 Env Antigen in a DNA Prime/Vaccinia Virus Boost Vaccine Regimen Is Time and Dose Dependent: Suppressive Effects of IL-12 Boost Are Mediated by Nitric Oxide J. Virol., July 15, 2000; 74(14): 6278 - 6286. [Abstract] [Full Text]

				J. C. Ramírez, M. M. Gherardi, and M. Esteban Biology of Attenuated Modified Vaccinia Virus Ankara Recombinant Vector in Mice: Virus Fate and Activation of B- and T-Cell Immune Responses in Comparison with the Western Reserve Strain and Advantages as a Vaccine J. Virol., January 1, 2000; 74(2): 923 - 933. [Abstract] [Full Text]