34 results on '"Jean, D"'
Search Results
2. Comparative ability of plasmid IL-12 and IL-15 to enhance cellular and humoral immune responses elicited by a SIVgag plasmid DNA vaccine and alter disease progression following SHIV 89.6P challenge in rhesus macaques
- Author
-
Chong, Siew-Yen, Egan, Michael A., Kutzler, Michele A., Megati, Shakuntala, Masood, Amjed, Roopchard, Vidia, Garcia-Hand, Dorys, Montefiori, David C., Quiroz, Jorge, Rosati, Margherita, Schadeck, Eva B., Boyer, Jean D., Pavlakis, George N., Weiner, David B., Sidhu, Maninder, Eldridge, John H., and Israel, Zimra R.
- Published
- 2007
- Full Text
- View/download PDF
3. A dose sparing effect by plasmid encoded IL-12 adjuvant on a SIVgag-plasmid DNA vaccine in rhesus macaques
- Author
-
Schadeck, Eva B., Sidhu, Maninder, Egan, Michael A., Chong, Siew-Yen, Piacente, Priscilla, Masood, Amjed, Garcia-Hand, Dorys, Cappello, Sarah, Roopchand, Vidia, Megati, Shakuntala, Quiroz, Jorge, Boyer, Jean D., Felber, Barbara K., Pavlakis, George N., Weiner, David B., Eldridge, John H., and Israel, Zimra R.
- Published
- 2006
- Full Text
- View/download PDF
4. Rhesus macaques with high levels of vaccine induced IFN-gamma producing cells better control viral set-point following challenge with SIV239
- Author
-
Boyer, Jean D., Maciag, Paulo C., Parkinson, Rose, Wu, Ling, Lewis, Mark G., Weiner, David B., and Paterson, Yvonne
- Published
- 2006
- Full Text
- View/download PDF
5. Efficacy of novel plasmid DNA encoding vaccinia antigens in improving current smallpox vaccination strategy
- Author
-
Otero, Miguel, Calarota, Sandra A., Dai, Anlan, De Groot, Anne S., Boyer, Jean D., and Weiner, David B.
- Published
- 2006
- Full Text
- View/download PDF
6. Plasmid vaccination of stable HIV-positive subjects on antiviral treatment results in enhanced CD8 T-cell immunity and increased control of viral “blips”
- Author
-
MacGregor, Rob Roy, Boyer, Jean D., Ugen, Kenneth E., Tebas, Pablo, Higgins, Terry J., Baine, Yaela, Ciccarelli, Richard B., Ginsberg, Richard S., and Weiner, David B.
- Published
- 2005
- Full Text
- View/download PDF
7. Resiquimod is a modest adjuvant for HIV-1 gag-based genetic immunization in a mouse model
- Author
-
Otero, Miguel, Calarota, Sandra A., Felber, Barbara, Laddy, Dominic, Pavlakis, George, Boyer, Jean D., and Weiner, David B.
- Published
- 2004
- Full Text
- View/download PDF
8. HIV-1 DNA vaccines and chemokines
- Author
-
Boyer, Jean D., Kim, Jong, Ugen, Ken, Cohen, Adam D., Ahn, Lois, Schumann, Kristen, Lacy, Kim, Bagarazzi, Mark L., Javadian, Ali, Ciccarelli, Richard B., Ginsberg, Richard S., MacGregor, Rob Roy, and Weiner, David B.
- Published
- 1999
- Full Text
- View/download PDF
9. High antibody and cellular responses induced to HIV-1 clade C envelope following DNA vaccines delivered by electroporation
- Author
-
Tatiana Arango, David B. Weiner, Jian Yan, Anlan Dai, Ruth M. Ruprecht, Jonathan LeCureux, David Montefiore, Michele A. Kutzler, Jiangmei Yin, Niranjan Y. Sardesai, Amir S. Khan, Jean D. Boyer, and Mark G. Lewis
- Subjects
Enzyme-Linked Immunospot Assay ,T-Lymphocytes ,medicine.medical_treatment ,HIV Infections ,HIV Antibodies ,Genes, env ,DNA vaccination ,Interferon-gamma ,Adjuvants, Immunologic ,Neutralization Tests ,Immunity ,Vaccines, DNA ,medicine ,Animals ,Humans ,Chemokine CCL5 ,AIDS Vaccines ,Immunity, Cellular ,General Veterinary ,General Immunology and Microbiology ,biology ,business.industry ,Electroporation ,Vaccination ,Public Health, Environmental and Occupational Health ,Viral Load ,Genes, gag ,Genes, pol ,Macaca mulatta ,Virology ,Immunity, Humoral ,Infectious Diseases ,Viral replication ,Antibody Formation ,Immunology ,HIV-1 ,biology.protein ,Human Immunodeficiency Virus DNA ,Molecular Medicine ,Simian Immunodeficiency Virus ,Antibody ,business ,Immunologic Memory ,Adjuvant - Abstract
Background Clade C is the predominant HIV-1 strain infecting people in sub-Saharan Africa, India, and China and there is a critical need for a vaccine targeted to these areas. In this study we tested a DNA based vaccine that encodes the SIVgag, SIVpol and HIV-1 envelope clade C. Methods Rhesus macaques were immunized by electroporation with the DNA plasmid encoding optimized SIVgag, SIVpol and an HIV-1 env clade C with or without the adjuvant RANTES. Animals were monitored for immune responses and challenged following the final immunization with 25 animal infectious doses (AID) of SHIV-1157ipd3N4. Results We found that the vaccine induced high levels of antigen specific IFN-γ producing effector cells and the capacity for CD4+ and CD8+ to proliferate upon antigen stimulation. Importantly, we found that the vaccine induced antibody titers as high as 1/4000. These antibodies were capable of neutralizing tier 1 HIV-1 viruses. Finally, when macaques were challenged with SHIV, viral loads were controlled in vaccinated groups. Conclusion We conclude that immunization with a simian/human immunodeficiency virus DNA-based vaccine delivered by electroporation can induce cellular and humoral immune responses that are able to control viral replication.
- Published
- 2011
10. Viral reservoir is suppressed but not eliminated by CD8 vaccine specific lymphocytes
- Author
-
Anlan Dai, Jean D. Boyer, Jonathan LeCureux, Mark G. Lewis, Jiangmei Yin, and Anding Shen
- Subjects
viruses ,Simian Acquired Immunodeficiency Syndrome ,Gene Products, gag ,CD8-Positive T-Lymphocytes ,Biology ,Virus Replication ,medicine.disease_cause ,Virus ,DNA vaccination ,Interferon-gamma ,Immune system ,Vaccines, DNA ,medicine ,Animals ,Cell Proliferation ,Immunity, Cellular ,General Veterinary ,General Immunology and Microbiology ,SAIDS Vaccines ,Public Health, Environmental and Occupational Health ,Viral Load ,Simian immunodeficiency virus ,biology.organism_classification ,Interleukin-12 ,Virology ,Infectious Diseases ,Viral replication ,Lentivirus ,Immunology ,Interleukin 12 ,Macaca ,Molecular Medicine ,Simian Immunodeficiency Virus ,Immunologic Memory ,Viral load - Abstract
It has long been postulated that while CD8 lymphocytes are capable of suppressing human immunodeficiency virus (HIV)-1 replication it is unlikely that the viral reservoirs once formed can be cleared. Our previous studies demonstrate that co-immunizing cynomologous macaques with a simian/human immunodeficiency virus (SHIV) DNA-based vaccines induces a strong cellular immune response that is able to suppress viral replication. We further demonstrated that interleukin (IL)-12 could significantly enhance the vaccine specific CD8 lymphocyte response. In this manuscript cynomologous macaques were vaccinated with a SHIV DNA-based vaccine co-delivered with IL-12. The macaques were then challenged with SHIV89.6p. Two years post-immunization and viral challenge we transiently depleted CD8(+) T cells. Plasma viral load increased, demonstrating the central role of CD8(+) T cells in viral suppression yet an inability to clear the viral reservoirs. Furthermore, in the data presented here, we found a higher number of IFN-gamma producing vaccine specific cells did not enhance suppression of viral replication.
- Published
- 2010
11. Comparative ability of plasmid IL-12 and IL-15 to enhance cellular and humoral immune responses elicited by a SIVgag plasmid DNA vaccine and alter disease progression following SHIV89.6P challenge in rhesus macaques
- Author
-
Vidia Roopchard, Amjed Masood, Zimra R. Israel, Michele A. Kutzler, Shakuntala Megati, Maninder K. Sidhu, Dorys Garcia-Hand, Margherita Rosati, John H. Eldridge, Siew-Yen Chong, George N. Pavlakis, Michael A. Egan, David B. Weiner, Eva B. Schadeck, Jean D. Boyer, David C. Montefiori, and Jorge Quiroz
- Subjects
CD4-Positive T-Lymphocytes ,Male ,Cellular immunity ,Simian Acquired Immunodeficiency Syndrome ,Gene Products, gag ,Enzyme-Linked Immunosorbent Assay ,CD8-Positive T-Lymphocytes ,Biology ,Antibodies, Viral ,DNA vaccination ,Interferon-gamma ,Immune system ,Plasmid ,Neutralization Tests ,Immunity ,Vaccines, DNA ,Animals ,Interleukin-15 ,Immunity, Cellular ,General Veterinary ,General Immunology and Microbiology ,Immunogenicity ,SAIDS Vaccines ,Public Health, Environmental and Occupational Health ,Interleukin-12 ,Macaca mulatta ,Virology ,CD4 Lymphocyte Count ,Infectious Diseases ,Antibody Formation ,Humoral immunity ,Immunology ,Disease Progression ,biology.protein ,Molecular Medicine ,Antibody ,Plasmids - Abstract
Plasmid-based IL-12 has been demonstrated to successfully enhance the immunogenicity of DNA vaccines, thus enabling a reduction of the amount of DNA required for immunization. IL-15 is thought to affect the maintenance and enhance effector function of CD8(+) memory T cells. Since the ability to elicit a long-term memory response is a desirable attribute of a prophylactic vaccine, we sought to evaluate the ability of these plasmid-based cytokines to serve as vaccine adjuvants in rhesus macaques. Macaques were immunized with plasmid DNA encoding SIVgag in combination with plasmid IL-12, IL-15, or a combination of IL-12 and IL-15. The plasmid-based cytokines were monitored for their ability to augment SIVgag-specific cellular and humoral immune responses and to alter the clinical outcome following pathogenic SHIV(89.6P) challenge. Macaques receiving SIVgag pDNA in combination with plasmid IL-12 alone, or in combination with plasmid IL-12 and IL-15, demonstrated significantly elevated cell-mediated and humoral immune responses resulting in an improved clinical outcome following virus challenge compared to macaques receiving SIVgag pDNA alone. Macaques receiving SIVgag pDNA in combination with plasmid IL-15 alone demonstrated minor increases in cell-mediated and humoral immune responses, however, the clinical outcome following virus challenge was not improved. These results have important implications for the continued development of plasmid DNA vaccines for the prevention of HIV-1 infection.
- Published
- 2007
12. Rhesus macaques with high levels of vaccine induced IFN-gamma producing cells better control viral set-point following challenge with SIV239
- Author
-
Yvonne Paterson, David B. Weiner, Paulo Cesar Maciag, Rose Parkinson, Mark G. Lewis, Ling Wu, and Jean D. Boyer
- Subjects
CD4-Positive T-Lymphocytes ,Male ,viruses ,animal diseases ,T cell ,Enzyme-Linked Immunosorbent Assay ,CD8-Positive T-Lymphocytes ,medicine.disease_cause ,DNA vaccination ,Interferon-gamma ,Immune system ,Antigen ,medicine ,Animals ,DNA Primers ,Immunity, Cellular ,Base Sequence ,General Veterinary ,General Immunology and Microbiology ,biology ,Public Health, Environmental and Occupational Health ,Viral Vaccines ,Viral Load ,biochemical phenomena, metabolism, and nutrition ,Simian immunodeficiency virus ,biology.organism_classification ,Macaca mulatta ,Virology ,Infectious Diseases ,medicine.anatomical_structure ,Viral replication ,Lentivirus ,Immunology ,RNA, Viral ,Molecular Medicine ,Female ,Simian Immunodeficiency Virus ,Viral load - Abstract
HIV-1 specific cellular immune responses play a significant part in controlling HIV-1 viral replication and are an important component of an HIV-1 vaccine induced immune response. We reported earlier that recombinant DNA vaccine delivered intramuscularly, and recombinant Listeria monocytogenes, delivered orally induced CD8+ and CD4+ T cell immune responses in rhesus macaques and that this vaccine protocol showed partial protection against an SIV239 challenge. In this paper, we have analyzed the SIV antigen-specific immune responses at the time of challenge and during the subsequent infection course. We find that the immune status of the animals, as measured by the frequency of antigen-specific IFN-gamma secreting peripheral blood mononuclear cells, at the time of challenge correlates more strongly with viral loads at set point than peak viral loads. The correlation between the immune response and viral load was strongest early, as viral set-point was just being established and disintegrates overtime. This study demonstrates the cellular immune response to SIV at the time of challenge of a nonhuman primate is able to impact on viral set-point following SIV239 challenge. Further, this study demonstrates that as virus replicates the T cell immune response to SIV antigens induced by the vaccine is modulated by antigen encountered by immune cells during viral replication.
- Published
- 2006
13. Plasmid vaccination of stable HIV-positive subjects on antiviral treatment results in enhanced CD8 T-cell immunity and increased control of viral ?blips?
- Author
-
Yaela Baine, David B. Weiner, Richard B. Ciccarelli, Richard S. Ginsberg, Terry J. Higgins, Rob Roy MacGregor, Pablo Tebas, Jean D. Boyer, and Kenneth E. Ugen
- Subjects
Adult ,Male ,Viremia ,CD8-Positive T-Lymphocytes ,HIV Antibodies ,Virus ,Double-Blind Method ,Antiretroviral Therapy, Highly Active ,HIV Seropositivity ,Vaccines, DNA ,medicine ,Humans ,HIV vaccine ,AIDS Vaccines ,General Veterinary ,General Immunology and Microbiology ,biology ,Public Health, Environmental and Occupational Health ,virus diseases ,Middle Aged ,biology.organism_classification ,medicine.disease ,Virology ,CD4 Lymphocyte Count ,Vaccination ,Infectious Diseases ,HIV Antigens ,Immunology ,Lentivirus ,RNA, Viral ,Molecular Medicine ,Female ,Viral disease ,Safety ,Viral load ,Plasmids - Abstract
Antiviral therapy prolongs suppression of viral replication and allows for significant immune reconstitution but has not been effective in eradicating reservoirs of virus, which produce resurgent viremia when highly active antiretroviral therapy (HAART) is discontinued. Immune-based therapy may provide an additional antiviral effect. We vaccinated stable HIV-positive patients on HAART with an HIV plasmid vaccine to determine safety, immunogenicity, and therapeutic potential. Volunteers received a combination of two HIV DNA plasmid constructs, which drive expression of env/rev and gag/pol genes. The vaccine was well tolerated with no toxicity. CD4 and CD8 lymphocyte counts did not change significantly among volunteers. CD8 MHC class I-restricted responses to HIV antigens were assayed. Eight of 13 vaccinees responded after vaccination with detectable ELISpot result. Importantly, we observed a difference in viral detection events in vaccinated compared to control patients. Three out of the five placebo recipients had "viral blips" (transient elevations of HIV RNA) during follow-up (10/49 assays) while these were only present in one of 13 vaccinees on one occasion (1/130 assays; p0.04). The decrease in the frequency of transient viremia and failure suggests that DNA immunization with CD8-generating vaccines in HAART-controlled HIV-positive subjects may have therapeutic potential.
- Published
- 2005
14. Issues for improving multiplasmid DNA vaccines for HIV-1
- Author
-
Joseph Kim, David B. Weiner, Velpandi Ayyavoo, Donghui Zhang, Karuppiah Muthumani, Sagar B. Kudchodkar, Jean D. Boyer, Mark L. Bagarazzi, and George N. Pavlakis
- Subjects
Cellular immunity ,Genes, vpr ,Genetic Vectors ,Dose-Response Relationship, Immunologic ,Drug Resistance ,Biology ,DNA vaccination ,Interferon-gamma ,Mice ,Antibiotic resistance ,Immune system ,Plasmid ,Antigen ,T-Lymphocyte Subsets ,Genes, Synthetic ,Vaccines, DNA ,Animals ,Humans ,Selection, Genetic ,Codon ,Promoter Regions, Genetic ,AIDS Vaccines ,Vaccines, Synthetic ,General Veterinary ,General Immunology and Microbiology ,Immunogenicity ,Vaccination ,Public Health, Environmental and Occupational Health ,biology.organism_classification ,Genes, rev ,Infectious Diseases ,Drug Design ,Immunology ,Lentivirus ,HIV-1 ,Molecular Medicine ,Safety ,Genetic Engineering - Abstract
Since the first reports of plasmid vaccines, there have been substantial changes made to the design of plasmid backbones, as well as to the antibiotic resistance markers chosen for clinical vectors compared with first generation vectors. These changes aid manufacturing, production and scale up and at the same time aid conceptual safety by limiting the ability of the vaccines to transfer useful genetic selection genes to other bacterial infectious agents. In contrast, there has been little change to the original promoters or polyadenlyation tracts in the last decade. We have learned that these first generation plasmid vaccines for HIV-1 appear very well tolerated in humans. However, while safe and immunogenic, improving the immune potency of DNA vaccines is a critical goal for this technology. The combination of antigens used should be carefully examined for possible immune interference. Such interference may only become apparent when each component of the vaccine is tested individually. This interference also suggests one mechanism of immune pathogenesis possibly by HIV-1. Optimization of the immune response can come through manipulation of the transfection efficiency, expression or through the use of various T cell and B cell plasmid adjuvants. It is likely that the combination of such advancements will significantly improve the clinical phenotype of this important vaccine modality.
- Published
- 2002
15. Safety and immunogenicity of HIV-1 DNA constructs in chimpanzees
- Author
-
David B. Weiner, Richard B. Ciccarelli, M. Ali Javadian, Ami Shah, Michael A. Chattergoon, Mark L. Bagarazzi, Leslie R. Coney, Mosi Bennett, Richard A. Carrano, Jean D. Boyer, and Kenneth E. Ugen
- Subjects
Male ,Cellular immunity ,Pan troglodytes ,HIV Infections ,chemical and pharmacologic phenomena ,Lymphocyte proliferation ,HIV Antibodies ,Biology ,Virus ,Immune system ,Pregnancy ,Vaccines, DNA ,Animals ,AIDS Vaccines ,General Veterinary ,General Immunology and Microbiology ,Immunogenicity ,Public Health, Environmental and Occupational Health ,biochemical phenomena, metabolism, and nutrition ,biology.organism_classification ,Virology ,Lymphocyte Subsets ,Disease Models, Animal ,Infectious Diseases ,Immunization ,DNA, Viral ,Humoral immunity ,Immunology ,Lentivirus ,HIV-1 ,bacteria ,Molecular Medicine ,Female - Abstract
A global effort to control the HIV epidemic is likely to rely heavily on immunization strategies. As our closest genetic relative, the chimpanzee provides the most important model for preclinical safety and immunogenicity studies. We have immunized adult, pregnant and infant chimpanzees with our plasmid vaccines. We have found these vaccines to be safe and well tolerated in all of these groups. The same vaccines have induced both humoral and cellular immunity in each instance.
- Published
- 1998
16. Development of a multicomponent candidate vaccine for HIV-1
- Author
-
Michael A. Chattergoon, Jong J. Kim, Bin Wang, Mark L. Bagarazzi, Jean D. Boyer, David B. Weiner, and Velpandi Ayyavoo
- Subjects
chemical and pharmacologic phenomena ,HIV Antibodies ,Biology ,DNA vaccination ,Mice ,Immune system ,Antigen ,Immunity ,Vaccines, DNA ,medicine ,Antigenic variation ,Animals ,AIDS Vaccines ,Acquired Immunodeficiency Syndrome ,Immunity, Cellular ,Mice, Inbred BALB C ,General Veterinary ,General Immunology and Microbiology ,Polyvalent Vaccine ,Immunogenicity ,Public Health, Environmental and Occupational Health ,T-Lymphocytes, Helper-Inducer ,T helper cell ,biochemical phenomena, metabolism, and nutrition ,Virology ,Infectious Diseases ,medicine.anatomical_structure ,DNA, Viral ,Immunology ,HIV-1 ,bacteria ,Molecular Medicine ,Female ,T-Lymphocytes, Cytotoxic - Abstract
Nucleic acid or DNA immunization represents a novel approach to both vaccine and immune therapeutic development. DNA vaccination induces antigen-specific cellular and humoral immune responses through the delivery of non-replicating transcription units which drive the synthesis of specific foreign proteins within the inoculated host. We have previously reported on the potential use of DNA immunization as a novel vaccine strategy for HIV-1. We found that both antigen-specific cellular and humoral immune responses could be induced in vivo with various DNA vaccine constructs against different antigenic targets within HIV-1. In order to enhance the DNA vaccine's ability to elicit cell-mediated immune responses, we co-delivered plasmids encoding costimulatory molecule B7 and interleukin-12 genes with DNA vaccine for HIV-1. We observed a dramatic increase in both antigen-specific T helper cell proliferation and CTL response. Eventual development of successful vaccines for HIV-1 would likely involve targeting multiple antigenic components of the virus to direct and empower the immune system to protect the host from viral infection. We present here the utility of multicomponent DNA immunization to elicit specific humoral and cell-mediated immune responses against different antigenic targets of HIV-1 as well as the ability of this immunization strategy to achieve significant enhancements of antigen-specific cellular immune responses.
- Published
- 1997
17. Immunologic consequences of chemotherapy for ovarian cancer: impaired responses to the influenza vaccine
- Author
-
Wade T. Rogers, Jean D. Boyer, Christina S. Chu, Eline T. Luning Prak, Abbas F. Jawad, Kathleen E. Sullivan, and Kenyetta McDonald
- Subjects
endocrine system diseases ,Cyclophosphamide ,Influenza vaccine ,medicine.medical_treatment ,Antineoplastic Agents ,Biology ,Antibodies, Viral ,Article ,Pharmacotherapy ,Drug Therapy ,Influenza, Human ,medicine ,Humans ,Ovarian Neoplasms ,Chemotherapy ,General Veterinary ,General Immunology and Microbiology ,ELISPOT ,Public Health, Environmental and Occupational Health ,Hemagglutination Inhibition Tests ,Middle Aged ,medicine.disease ,Infectious Diseases ,Vaccines, Inactivated ,Influenza Vaccines ,Immunology ,biology.protein ,Leukocytes, Mononuclear ,Molecular Medicine ,Monoclonal B-cell lymphocytosis ,Female ,Antibody ,Ovarian cancer ,medicine.drug - Abstract
To examine the effect of chemotherapy for ovarian cancer on immunologic function and to define the effect on the serologic response to the influenza vaccine.Under IRB approved protocols, patients with ovarian cancer were administered seasonal trivalent killed influenza vaccines. Peripheral blood was collected for immunologic assessments. Serum was analyzed for hemagglutination inhibition (HAI) antibody titers. Peripheral blood mononuclear cells were isolated to characterize T and B cell populations and function.Thirty-one patients were recruited: 13 in remission receiving a dendritic cell vaccine with or without a single dose of low-dose cyclophosphamide, 3 in remission not receiving treatment, and 15 undergoing standard therapy. Significant effects on T cell and B cell subset distributions were seen. Functional effects were also seen. Few patients were able to mount a 4-fold HAI antibody response. A 4-fold response was observed for H1N1 in 20%, for H3N2 in 26%, and for influenza B in 6%. Pre-existing exposure to influenza was predictive of responders.Despite CDC recommendations that patients undergoing chemotherapy receive influenza vaccine, there is little evidence to support its serologic effectiveness in this population. Patients with ovarian cancer are almost uniformly unable to mount a meaningful antibody response. These findings have serious implications for future resource allocation for both seasonal and novel pandemic influenza outbreak and understanding the immunologic deficits as a result of chemotherapy may improve patient care.
- Published
- 2013
18. Facilitated DNA inoculation induces anti-HIV-1 immunity in vivo
- Author
-
Catherine J. Pachuk, Jean D. Boyer, Kesen Deng, M.J. Newman, David B. Weiner, Kenneth E. Ugen, William V. Williams, Daniel E. Mccallus, Karin Moelling, Kathleen Herold, Bin Wang, Michael G. Agadjanyan, Lori Gilbert, Michael Merva, Leslie R. Coney, and Vasantha Srikantan
- Subjects
Cellular immunity ,Biology ,HIV Envelope Protein gp160 ,Immune system ,Antigen ,Immunity ,Animals ,Humans ,Protein Precursors ,AIDS Vaccines ,Attenuated vaccine ,General Veterinary ,General Immunology and Microbiology ,Public Health, Environmental and Occupational Health ,Gene Products, env ,Virology ,Fusion Proteins, gag-pol ,Vaccination ,Infectious Diseases ,HIV Antigens ,DNA, Viral ,Humoral immunity ,Immunology ,HIV-1 ,Molecular Medicine ,T-Lymphocytes, Cytotoxic - Abstract
Vaccine design against HIV-1 is complicated both by the latent aspects of lentiviral infection and the diversity of the virus. The type of vaccine approach used is therefore likely to be critically important. In general, vaccination strategies have relied on the use of live attenuated material or inactivated/subunit preparations as specific immunogens. Each of these methodologies has advantages and disadvantages in terms of the elicitation of broad cellular and humoral immune responses. Although most success has been achieved with live attenuated vaccines, there is a conceptual safety concern associated with the use of these vaccines for the prevention of human infections. In contrast, subunit or killed vaccine preparations enjoy advantages in preparation and conceptual safety; however, their ability to elicit broad immunity is more limited. In theory, inoculation of a plasmid DNA that supports in vivo expression of proteins, and therefore presentation of the processed protein antigen to the immune system, could be used to combine the features of a subunit vaccine and a live attenuated vaccine. We have designed a strategy for intramuscular DNA inoculation to elicit humoral and cellular immune responses against expressed HIV antigens. Uptake and expression are significantly enhanced if DNA is administered in conjunction with the facilitating agent bupivacaine-HCl. Using this technique we have demonstrated functional cellular and humoral immune responses against the majority of HIV-1 encoded antigens in both rodents and non-human primates.
- Published
- 1994
19. A dose sparing effect by plasmid encoded IL-12 adjuvant on a SIVgag-plasmid DNA vaccine in rhesus macaques
- Author
-
John H. Eldridge, George N. Pavlakis, Shakuntala Megati, Vidia Roopchand, Priscilla Piacente, Barbara K. Felber, Jorge Quiroz, David B. Weiner, Zimra R. Israel, Sarah Cappello, Eva B. Schadeck, Dorys Garcia-Hand, Maninder K. Sidhu, Siew-Yen Chong, Jean D. Boyer, Michael A. Egan, and Amjed Masood
- Subjects
Vaccination schedule ,viruses ,animal diseases ,medicine.medical_treatment ,Gene Products, gag ,Enzyme-Linked Immunosorbent Assay ,Biology ,medicine.disease_cause ,Antibodies, Viral ,Immune system ,Adjuvants, Immunologic ,Immunopathology ,medicine ,Vaccines, DNA ,Animals ,Immunity, Cellular ,General Veterinary ,General Immunology and Microbiology ,ELISPOT ,Public Health, Environmental and Occupational Health ,Simian immunodeficiency virus ,Virology ,Interleukin-12 ,Macaca mulatta ,Vaccination ,Infectious Diseases ,Cytokine ,Immunology ,Molecular Medicine ,Simian Immunodeficiency Virus ,Adjuvant ,Plasmids - Abstract
An experimental pDNA vaccine adjuvant expressing IL-12 was evaluated for its ability to augment the humoral and cellular immune responses elicited by a SIVmac239 gag p39 expressing pDNA vaccine. To determine the effect of vaccine dose on the immune response, rhesus macaques were immunized with 1.5 mg or 5.0 mg of SIVmac239 gag pDNA, with or without co-immunization of IL-12 pDNA at 1.5 mg and 5.0 mg, respectively. Serum antibody responses to simian immunodeficiency virus (SIV) gag were increased 10-fold ( p = 0.044, 0.002) in macaques receiving IL-12 pDNA. Cellular immune responses, monitored by SIV gag-specific IFN-γ ELISpot assay, were also significantly higher ( p = 0.007, 0.019) when the pDNA vaccine was co-immunized with IL-12 pDNA at high and low doses. There was no statistical difference between the immune responses elicited by the high and low dose of IL-12 pDNA ( p = 0.221, 0.917), a finding which could allow a dose reduction of vaccine without the concomitant loss of imunogenicity. Furthermore, analysis of the breadth of the T-cell response during the vaccination schedule, using overlapping peptides to SIV gag, demonstrated a significant correlation ( p = 0.0002) between the magnitude and breadth of the immune responses in the vaccines. These results have important implications for the continuing development of an effective, safe low dose pDNA vaccine adjuvant suitable for human use.
- Published
- 2005
20. Efficacy of novel plasmid DNA encoding vaccinia antigens in improving current smallpox vaccination strategy
- Author
-
Miguel Otero, Sandra A. Calarota, Jean D. Boyer, David B. Weiner, Anlan Dai, and Anne S. De Groot
- Subjects
Cellular immunity ,viruses ,Vaccinia virus ,Biology ,Virus ,DNA vaccination ,chemistry.chemical_compound ,Interferon-gamma ,Mice ,Plasmid ,Vaccines, DNA ,Animals ,Cloning, Molecular ,Smallpox vaccine ,Antigens, Viral ,DNA Primers ,Mice, Inbred BALB C ,General Veterinary ,General Immunology and Microbiology ,Base Sequence ,Public Health, Environmental and Occupational Health ,virus diseases ,Flow Cytometry ,Virology ,Vaccination ,Mice, Inbred C57BL ,Infectious Diseases ,chemistry ,Humoral immunity ,Immunology ,Molecular Medicine ,Female ,Vaccinia ,Smallpox Vaccine ,Plasmids - Abstract
We tested a DNA vaccine strategy in order to improve the efficacy and safety of the current live smallpox vaccine involving priming with DNA vaccines and boosting with live vaccinia virus (VacV). We generated DNA plasmids encoding the A4L, A27L and H5R VacV genes. A considerable increase in antigen-specific IFN-gamma responses, high proliferative and humoral antigen-specific responses were detected in experimental primed Balb/C mice compared to controls after VacV boost. The VacV-DNA plasmids elicited IFN-gamma production in HLA-A2.1 transgenic mice in response to predicted HLA-A2.1 restricted peptide epitopes, providing valuable data for further vaccine development.
- Published
- 2005
21. Resiquimod is a modest adjuvant for HIV-1 gag-based genetic immunization in a mouse model
- Author
-
George Pavlakis, Jean D. Boyer, Dominick Laddy, Sandra A. Calarota, David B. Weiner, Barbara Felber, and Miguel Otero
- Subjects
medicine.medical_treatment ,Gene Products, gag ,Context (language use) ,Biology ,CD8-Positive T-Lymphocytes ,HIV Antibodies ,Injections, Intramuscular ,DNA vaccination ,chemistry.chemical_compound ,Interferon-gamma ,Mice ,Immune system ,Adjuvants, Immunologic ,medicine ,Vaccines, DNA ,Animals ,Lymphocyte Count ,AIDS Vaccines ,Immunity, Cellular ,Mice, Inbred BALB C ,General Veterinary ,General Immunology and Microbiology ,ELISPOT ,Public Health, Environmental and Occupational Health ,Antibody titer ,Imidazoles ,Virology ,Infectious Diseases ,chemistry ,Immunoglobulin G ,Immunology ,Antibody Formation ,biology.protein ,Molecular Medicine ,Cytokines ,Female ,Resiquimod ,Antibody ,Adjuvant ,Plasmids - Abstract
DNA vaccines have been effective at generating useful immune responses in many animal species. However, it is clearly desirable to increase their potency. The identification of adjuvants that increase their cell-mediated immune (CMI) response is therefore an important goal. Resiquimod is an imiquimod analog proven to activate dendritic cells through TLR-7. The adjuvant capacity of resiquimod has not, to our knowledge, been studied in the context of genetic immunization. Here, we studied resiquimod as an adjuvant for plasmid vaccine therapy by intra-muscular immunization of BALB/c mice with HIV-1 gag DNA vaccine without and with several concentrations of resiquimod (ranging from 5-100nM). We observed that resiquimod moderately enhanced IFN-gamma production as measured by a peptide-based ELISPOT assay compared to that obtained in mice immunized with DNA gag only. Antigen-specific T-cell proliferation studies showed a several-fold increase in the stimulation index in mice immunized with DNA gag +50 nM of resiquimod as compared to mice receiving DNA gag alone. Antibody titer also increased, while the antibody isotyping data showed a strong Th1 biased type response. Analysis of cytokine production in serum samples demonstrated a stronger Th1 cytokine bias in the presence of resiquimod. Furthermore, relevant increase in IL-4 production, as measured by ELISPOT assay, was not observed. Our results show that resiquimod can have modest adjuvant activity, in a DNA formulation, driving the immune system towards a cell-mediated immune response. Additional studies involving this adjuvant for DNA vaccines are underway.
- Published
- 2004
22. A Gag-Pol/Env-Rev SIV239 DNA vaccine improves CD4 counts, and reduce viral loads after pathogenic intrarectal SIV(mac)251 challenge in rhesus Macaques
- Author
-
Dan Conway, Zimmra Israel, David B. Weiner, Richard B. Ciccarelli, Jong Kim, David C. Montefiori, Jean D. Boyer, Nancy Miller, Kenneth E. Ugen, Karuppiah Muthumani, Kelledy Manson, Mark L. Bagarazzi, and Daniel S. Hwang
- Subjects
viruses ,Simian Acquired Immunodeficiency Syndrome ,Biology ,medicine.disease_cause ,DNA vaccination ,medicine ,Vaccines, DNA ,Animals ,General Veterinary ,General Immunology and Microbiology ,SAIDS Vaccines ,Vaccination ,Public Health, Environmental and Occupational Health ,Gene Products, env ,Simian immunodeficiency virus ,Viral Load ,biology.organism_classification ,Virology ,Macaca mulatta ,CD4 Lymphocyte Count ,Fusion Proteins, gag-pol ,Infectious Diseases ,HIV Antigens ,Gene Products, rev ,Immunology ,Lentivirus ,Molecular Medicine ,Viral disease ,Viral load - Abstract
DNA vaccines are an important vaccine approach for many infectious diseases including human immunodeficiency virus (HIV). Recently, there have been exciting results reported for plasmid vaccination in pathogenic SHIV model systems. In these studies, plasmid vaccines supplemented by IL-2 Ig cytokine gene adjuvants or boosted by recombinant MVA vectors expressing relevant SIV and HIV antigens prevented CD4(+) T-cell loss and lowered viral loads following pathogenic challenge. However, similar results have not been reported in a direct pathogenic macaque challenge model. Here we report on a study of the ability of a multiplasmid SIV DNA vaccine in a pathogenic SIV251 rhesus mucosal challenge study. We observed that pGag/Pol+pEnv/Rev plasmid vaccines could not prevent SIV infection; however, vaccinated animals exhibited significant improvement in control of viral challenge compared to control animals. Furthermore, vaccinated animals exhibited protection against CD4(+) T-cell loss.
- Published
- 2003
23. Immunologic consequences of chemotherapy for ovarian cancer: Impaired responses to the influenza vaccine
- Author
-
Chu, Christina S., primary, Boyer, Jean D., additional, Jawad, Abbas, additional, Mcdonald, Kenyetta, additional, Rogers, Wade T., additional, Luning Prak, Eline T., additional, and Sullivan, Kathleen E., additional
- Published
- 2013
- Full Text
- View/download PDF
24. HIV-1 DNA vaccines and chemokines
- Author
-
David B. Weiner, Richard B. Ciccarelli, Mark L. Bagarazzi, Kristen Schumann, Jean D. Boyer, Kenneth E. Ugen, Rob Roy MacGregor, Richard S. Ginsberg, Adam D. Cohen, Ali Javadian, Kim Lacy, Lois Ahn, and Jong Kim
- Subjects
Cellular immunity ,Chemokine ,Pan troglodytes ,Virus ,DNA vaccination ,Mice ,Plasmid ,Immune system ,Tumor Cells, Cultured ,Animals ,Humans ,AIDS Vaccines ,Clinical Trials as Topic ,Mice, Inbred BALB C ,General Veterinary ,General Immunology and Microbiology ,biology ,Immunogenicity ,Public Health, Environmental and Occupational Health ,Virology ,Infectious Diseases ,Immunology ,Humoral immunity ,DNA, Viral ,biology.protein ,HIV-1 ,Molecular Medicine ,Female ,Chemokines - Abstract
DNA vaccines have a demonstrated ability to induce humoral and cellular immune responses in animal models and humans. The technology, although it dates back to the 1950's, has had an insurgence of interest within the past few years following concurrent research papers. The basic technology is being applied broadly to viral, bacterial and parasitic infections. It has also been demonstrated that genes delivered via plasmid expression vectors result in expression of functional proteins in the inoculated host. Further, injection of plasmids encoding cytokine, chemokine or co-stimulatory molecules, also referred to as immunomodulatory plasmids can lead to the further expansion of this technology to include directed immunology. We have been developing DNA technology specifically with a focus as a vaccine against HIV-1 infection. We report that such vaccines can stimulate immune responses in a variety of relevant animal systems including humoral and cellular responses as well as the production of beta-chemokines. We describe that the beta-chemokines can both modulate the immune response induced by DNA vaccines and be modulated by the DNA vaccines in the murine and chimpanzee models as well as in humans.
- Published
- 1999
25. Mucosal immunization with a DNA vaccine induces immune responses against HIV-1 at a mucosal site
- Author
-
Michael J. Merva, David B. Weiner, Feng Li, Kesen Dang, Michael G. Agadjanyan, Jean D. Boyer, William V. Williams, Kenneth E. Ugen, Vasantha Srikantan, and Bin Wang
- Subjects
Enzyme-Linked Immunosorbent Assay ,HIV Antibodies ,Virus ,DNA vaccination ,HIV Envelope Protein gp160 ,Mice ,Immune system ,Genes, Reporter ,Vaccines, DNA ,Animals ,Immunity, Mucosal ,AIDS Vaccines ,Acquired Immunodeficiency Syndrome ,General Veterinary ,General Immunology and Microbiology ,biology ,Public Health, Environmental and Occupational Health ,beta-Galactosidase ,Virology ,Mucosal Infection ,Administration, Intravaginal ,Infectious Diseases ,Immunization ,Humoral immunity ,Immunology ,DNA, Viral ,biology.protein ,HIV-1 ,Molecular Medicine ,Female ,Antibody - Abstract
Mucosal immunity is the first defense system in protection against mucosal infection by sexually transmitted diseases and subsequent systemic dissemination of infection. Development of vaccines which can induce protective mucosal immunity would have great promise for preventing sexually transmitted diseases including AIDS. DNA vaccines have recently shown certain advantages over other types of vaccines in safety and elicitation of specific immune responses. We have hypothesized that direct delivery of a DNA plasmid coding the HIV-1 envelope (pcMN160) via mucosal routes will stimulate mucosal immunity against HIV-1. The expression of DNA plasmid inoculated intravaginally was detected in various tissues. Intravaginal inoculation of pcMN160 elicits production of vaginal immunoglobulins which specifically bind to the HIV-1 envelope and neutralize HIV-1 infectivity in vitro. These results indicate the feasibility of inducing mucosal immunity following mucosal inoculation of DNA vaccines. When coupled with systemic inoculation of appropriate DNA constructs, effective mucosal and systemic immunity may be generated.
- Published
- 1997
26. Nucleic acid immunization of chimpanzees as a prophylactic/immunotherapeutic vaccination model for HIV-1: prelude to a clinical trial
- Author
-
David B. Weiner, Richard B. Ciccarelli, Pat Frost, Michael G. Agadjanyan, Jean D. Boyer, William V. Williams, Ali Javadian, Michael Merva, Mark L. Bagarazzi, Kenneth E. Ugen, Leslie R. Coney, Susan B. Nyland, and Bin Wang
- Subjects
Cellular immunity ,Pan troglodytes ,Molecular Sequence Data ,Drug Evaluation, Preclinical ,chemical and pharmacologic phenomena ,HIV Infections ,HIV Antibodies ,Immune system ,Vaccines, DNA ,Animals ,Amino Acid Sequence ,AIDS Vaccines ,General Veterinary ,General Immunology and Microbiology ,biology ,Immunogenicity ,Vaccination ,Public Health, Environmental and Occupational Health ,Virology ,CTL ,Disease Models, Animal ,Infectious Diseases ,Immunization ,Humoral immunity ,Immunology ,DNA, Viral ,biology.protein ,HIV-1 ,Molecular Medicine ,Antibody ,T-Lymphocytes, Cytotoxic - Abstract
Vaccine development strategies have often utilized recombinant envelope glycoproteins which usually generate strong humoral immune responses but which do not generate strong cytotoxic T lymphyocytes (CTL). A recent novel experimental vaccination approach involves the technology known as nucleic acid immunization in which DNA plasmids expressing a gene of interest is injected intramuscularly in experimental animals. These expressed proteins then are presented to the immune system with the subsequent development of strong antibody and cellular (particularly CTL) immune responses. These types of immune responses have been elicited in rodents as well as nonhuman primates including chimpanzees. Results from studies on nucleic acid immunization of HIV-1 infected chimpanzees with envelope glycoprotein expressing constructs indicated that this method was able to decrease substantially HIV-1 viral load in these chimpanzees. These data are useful for the development and implementation of human phase 1 clinical trials with HIV constructs expressing various genes from the HIV-1 genome.
- Published
- 1997
27. Inclusion of a CRF01_AE HIV envelope protein boost with a DNA/MVA prime-boost vaccine: Impact on humoral and cellular immunogenicity and viral load reduction after SHIV-E challenge
- Author
-
Cox, Josephine H., primary, Ferrari, Maria G., additional, Earl, Patricia, additional, Lane, James R., additional, Jagodzinski, Linda L., additional, Polonis, Victoria R., additional, Kuta, Ellen G., additional, Boyer, Jean D., additional, Ratto-Kim, Silvia, additional, Eller, Leigh-Anne, additional, Pham, Doan-Trang, additional, Hart, Lydia, additional, Montefiori, David, additional, Ferrari, Guido, additional, Parrish, Stephanie, additional, Weiner, David B., additional, Moss, Bernard, additional, Kim, Jerome H., additional, Birx, Deborah, additional, and VanCott, Thomas C., additional
- Published
- 2012
- Full Text
- View/download PDF
28. High antibody and cellular responses induced to HIV-1 clade C envelope following DNA vaccines delivered by electroporation
- Author
-
Yin, Jiangmei, primary, Dai, Anlan, additional, LeCureux, Jonathan, additional, Arango, Tatiana, additional, Kutzler, Michele A., additional, Yan, Jian, additional, Lewis, Mark G., additional, Khan, Amir, additional, Sardesai, Niranjan Y., additional, Montefiore, David, additional, Ruprecht, Ruth, additional, Weiner, David B., additional, and Boyer, Jean D., additional
- Published
- 2011
- Full Text
- View/download PDF
29. Viral reservoir is suppressed but not eliminated by CD8 vaccine specific lymphocytes
- Author
-
Yin, Jiangmei, primary, Dai, Anlan, additional, Shen, Anding, additional, LeCureux, Jonathan, additional, Lewis, Mark G., additional, and Boyer, Jean D., additional
- Published
- 2010
- Full Text
- View/download PDF
30. Comparative ability of plasmid IL-12 and IL-15 to enhance cellular and humoral immune responses elicited by a SIVgag plasmid DNA vaccine and alter disease progression following SHIV89.6P challenge in rhesus macaques
- Author
-
Chong, Siew-Yen, primary, Egan, Michael A., additional, Kutzler, Michele A., additional, Megati, Shakuntala, additional, Masood, Amjed, additional, Roopchard, Vidia, additional, Garcia-Hand, Dorys, additional, Montefiori, David C., additional, Quiroz, Jorge, additional, Rosati, Margherita, additional, Schadeck, Eva B., additional, Boyer, Jean D., additional, Pavlakis, George N., additional, Weiner, David B., additional, Sidhu, Maninder, additional, Eldridge, John H., additional, and Israel, Zimra R., additional
- Published
- 2007
- Full Text
- View/download PDF
31. Safety and immunogenicity of HIV-1 DNA constructs in chimpanzees
- Author
-
Bagarazzi, Mark L., primary, Boyer, Jean D., additional, Ugen, Kenneth E., additional, Ali Javadian, M., additional, Chattergoon, Michael, additional, Shah, Ami, additional, Bennett, Mosi, additional, Ciccarelli, Richard, additional, Carrano, Richard, additional, Coney, Leslie, additional, and Weiner, David B., additional
- Published
- 1998
- Full Text
- View/download PDF
32. DNA vaccination with HIV-1 expressing constructs elicits immune responses in humans
- Author
-
Ugen, Kenneth E., primary, Nyland, Susan B., additional, Boyer, Jean D., additional, Vidal, Cristina, additional, Lera, Liana, additional, Rasheid, Sowsan, additional, Chattergoon, Michael, additional, Bagarazzi, Mark L., additional, Ciccarelli, Richard, additional, Higgins, Terry, additional, Baine, Yaila, additional, Ginsberg, Richard, additional, Macgregor, Rob Roy, additional, and Weiner, David B., additional
- Published
- 1998
- Full Text
- View/download PDF
33. Development of a multicomponent candidate vaccine for HIV-1
- Author
-
Kim, Jong J., primary, Ayyavoo, Velpandi, additional, Bagarazzi, Mark L., additional, Chattergoon, Michael, additional, Boyer, Jean D., additional, Wang, Bin, additional, and Weiner, David B., additional
- Published
- 1997
- Full Text
- View/download PDF
34. Nucleic acid immunization of chimpanzees as a prophylactic/immunotherapeutic vaccination model for HIV-1: prelude to a clinical trial
- Author
-
Ugen, Kenneth E., primary, Boyer, Jean D., additional, Wang, Bin, additional, Bagarazzi, Mark, additional, Javadian, Ali, additional, Frost, Pat, additional, Merva, Michael M., additional, Agadjanyan, Michael G., additional, Nyland, Susan, additional, Williams, William V., additional, Coney, Leslie, additional, Ciccarelli, Richard, additional, and Weiner, David B., additional
- Published
- 1997
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.