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Science 19 March 1993:
Vol. 259. no. 5102, pp. 1745 - 1749
DOI: 10.1126/science.8456302
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Articles

Science, Vol 259, Issue 5102, 1745-1749
Copyright © 1993 by American Association for the Advancement of Science

articles

Heterologous protection against influenza by injection of DNA encoding a viral protein

JB Ulmer, JJ Donnelly, SE Parker, GH Rhodes, PL Felgner, VJ Dwarki, SH Gromkowski, RR Deck, CM DeWitt, A Friedman, and al. et

Department of Cancer Research, Merck Research Laboratories, West Point, PA 19486.

Cytotoxic T lymphocytes (CTLs) specific for conserved viral antigens can respond to different strains of virus, in contrast to antibodies, which are generally strain-specific. The generation of such CTLs in vivo usually requires endogenous expression of the antigen, as occurs in the case of virus infection. To generate a viral antigen for presentation to the immune system without the limitations of direct peptide delivery or viral vectors, plasmid DNA encoding influenza A nucleoprotein was injected into the quadriceps of BALB/c mice. This resulted in the generation of nucleoprotein-specific CTLs and protection from a subsequent challenge with a heterologous strain of influenza A virus, as measured by decreased viral lung titers, inhibition of mass loss, and increased survival.


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Human Metapneumovirus Fusion Protein Vaccines That Are Immunogenic and Protective in Cotton Rats.
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J. Virol. 81, 903-916
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R. Wang, T. L. Richie, M. F. Baraceros, N. Rahardjo, T. Gay, J.-G. Banania, Y. Charoenvit, J. E. Epstein, T. Luke, D. A. Freilich, et al. (2005)
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Neutralizing Antibodies Elicited by Immunization of Monkeys with DNA Plasmids and Recombinant Adenoviral Vectors Expressing Human Immunodeficiency Virus Type 1 Proteins.
J. R. Mascola, A. Sambor, K. Beaudry, S. Santra, B. Welcher, M. K. Louder, T. C. VanCott, Y. Huang, B. K. Chakrabarti, W.-P. Kong, et al. (2005)
J. Virol. 79, 771-779
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Gene Vaccination to Bias the Immune Response to Amyloid-{beta} Peptide as Therapy for Alzheimer Disease.
B. Qu, R. N. Rosenberg, L. Li, P. J. Boyer, and S. A. Johnston (2004)
Arch Neurol 61, 1859-1864
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Protective Efficacy of a DNA Influenza Virus Vaccine Is Markedly Increased by the Coadministration of a Schiff Base-Forming Drug.
J. Charo, J. A. Lindencrona, L.-M. Carlson, J. Hinkula, and R. Kiessling (2004)
J. Virol. 78, 11321-11326
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Priming with CpG-enriched plasmid and boosting with protein formulated with CpG oligodeoxynucleotides and Quil A induces strong cellular and humoral immune responses to hepatitis C virus NS3.
H. Yu, L. A. Babiuk, and S. van Drunen Littel-van den Hurk (2004)
J. Gen. Virol. 85, 1533-1543
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DNA Vaccines against Human Immunodeficiency Virus Type 1 in the Past Decade.
M. Giri, K. E. Ugen, and D. B. Weiner (2004)
Clin. Microbiol. Rev. 17, 370-389
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Intraspleen Delivery of a DNA Vaccine Coding for Superoxide Dismutase (SOD) of Brucella abortus Induces SOD-Specific CD4+ and CD8+ T Cells.
C. Munoz-Montesino, E. Andrews, R. Rivers, A. Gonzalez-Smith, G. Moraga-Cid, H. Folch, S. Cespedes, and A. A. Onate (2004)
Infect. Immun. 72, 2081-2087
   Abstract »    Full Text »    PDF »
Persistency of Adenoviral-Mediated Lysostaphin Expression in Goat Mammary Glands.
W. Fan, K. Plaut, A. J. Bramley, J. W. Barlow, S. A. Mischler, and D. E. Kerr (2004)
J Dairy Sci 87, 602-608
   Abstract »    Full Text »    PDF »
Recognition of Homo- and Heterosubtypic Variants of Influenza A Viruses by Human CD8+ T Lymphocytes.
A. C. M. Boon, G. de Mutsert, D. van Baarle, D. J. Smith, A. S. Lapedes, R. A. M. Fouchier, K. Sintnicolaas, A. D. M. E. Osterhaus, and G. F. Rimmelzwaan (2004)
J. Immunol. 172, 2453-2460
   Abstract »    Full Text »    PDF »
Systemic Administration of IL-18 Promotes Diabetes Development in Young Nonobese Diabetic Mice.
Y. Oikawa, A. Shimada, A. Kasuga, J. Morimoto, T. Osaki, H. Tahara, T. Miyazaki, F. Tashiro, E. Yamato, J.-i. Miyazaki, et al. (2003)
J. Immunol. 171, 5865-5875
   Abstract »    Full Text »    PDF »
A DNA Vaccine Encoding Cu,Zn Superoxide Dismutase of Brucella abortus Induces Protective Immunity in BALB/c Mice.
A. A. Onate, S. Cespedes, A. Cabrera, R. Rivers, A. Gonzalez, C. Munoz, H. Folch, and E. Andrews (2003)
Infect. Immun. 71, 4857-4861
   Abstract »    Full Text »    PDF »
Prime-Boost Vaccination with HIV-1 Gag Protein and Cytosine Phosphate Guanosine Oligodeoxynucleotide, Followed by Adenovirus, Induces Sustained and Robust Humoral and Cellular Immune Responses.
M. Tritel, A. M. Stoddard, B. J. Flynn, P. A. Darrah, C.-y. Wu, U. Wille, J. A. Shah, Y. Huang, L. Xu, M. R. Betts, et al. (2003)
J. Immunol. 171, 2538-2547
   Abstract »    Full Text »    PDF »
Induction of Broad and Potent Anti-Human Immunodeficiency Virus Immune Responses in Rhesus Macaques by Priming with a DNA Vaccine and Boosting with Protein-Adsorbed Polylactide Coglycolide Microparticles.
G. Otten, M. Schaefer, C. Greer, M. Calderon-Cacia, D. Coit, J. Kazzaz, A. Medina-Selby, M. Selby, M. Singh, M. Ugozzoli, et al. (2003)
J. Virol. 77, 6087-6092
   Abstract »    Full Text »    PDF »
On the Use of DNA Vaccines for the Prophylaxis of Mycobacterial Diseases.
K. Huygen (2003)
Infect. Immun. 71, 1613-1621
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Optimization of DNA-based Vaccination in Cows Using Green Fluorescent Protein and Protein A as a Prelude to Immunization Against Staphylococcal Mastitis.
E. W. Carter and D. E. Kerr (2003)
J Dairy Sci 86, 1177-1186
   Abstract »    Full Text »    PDF »
Gene Vaccines.
I. K. Srivastava and M. A. Liu (2003)
Ann Intern Med 138, 550-559
   Abstract »    Full Text »    PDF »
Effective Protective Immunity to Yersinia pestis Infection Conferred by DNA Vaccine Coding for Derivatives of the F1 Capsular Antigen.
H. Grosfeld, S. Cohen, T. Bino, Y. Flashner, R. Ber, E. Mamroud, C. Kronman, A. Shafferman, and B. Velan (2003)
Infect. Immun. 71, 374-383
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DNA Immunization with Hepatitis C Virus (HCV) Polycistronic Genes or Immunization by HCV DNA Priming-Recombinant Canarypox Virus Boosting Induces Immune Responses and Protection from Recombinant HCV-Vaccinia Virus Infection in HLA-A2.1-Transgenic Mice.
P. Pancholi, M. Perkus, N. Tricoche, Q. Liu, and A. M. Prince (2002)
J. Virol. 77, 382-390
   Abstract »    Full Text »    PDF »
Marked Enhancement of the Antigen-Specific Immune Response by Combining Plasmid DNA-Based Immunization with a Schiff Base-Forming Drug.
J. Charo, M. Sundback, K. Wasserman, A.-M. T. Ciupitu, B. Mirzai, R. van der Zee, and R. Kiessling (2002)
Infect. Immun. 70, 6652-6657
   Abstract »    Full Text »    PDF »
Efficient Priming of CD4+ and CD8+ T Cells by DNA Vaccination Depends on Appropriate Targeting of Sufficient Levels of Immunologically Relevant Antigen to Appropriate Processing Pathways.
C. Rush, T. Mitchell, and P. Garside (2002)
J. Immunol. 169, 4951-4960
   Abstract »    Full Text »    PDF »
Vaccination with Minigenes Encoding VH-derived Major Histocompatibility Complex Class I-binding Epitopes Activates Cytotoxic T Cells that Ablate Autoantibody-producing B Cells and Inhibit Lupus.
G.-C. Fan and R. R. Singh (2002)
J. Exp. Med. 196, 731-741
   Abstract »    Full Text »    PDF »
Structural Elements of a Protein Antigen Determine Immunogenicity of the Embedded MHC Class I-Restricted T Cell Epitope.
W. Paster, M. Kalat, M. Zehetner, and T. Schweighoffer (2002)
J. Immunol. 169, 2937-2946
   Abstract »    Full Text »    PDF »
Safety and Immunogenicity of a DNA Vaccine Encoding Carcinoembryonic Antigen and Hepatitis B Surface Antigen in Colorectal Carcinoma Patients.
R. M. Conry, D. T. Curiel, T. V. Strong, S. E. Moore, K. O. Allen, D. L. Barlow, D. R. Shaw, and A. F. LoBuglio (2002)
Clin. Cancer Res. 8, 2782-2787
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A DNA Vaccine Encoding Lumazine Synthase from Brucella abortus Induces Protective Immunity in BALB/c Mice.
C. A. Velikovsky, J. Cassataro, G. H. Giambartolomei, F. A. Goldbaum, S. Estein, R. A. Bowden, L. Bruno, C. A. Fossati, and M. Spitz (2002)
Infect. Immun. 70, 2507-2511
   Abstract »    Full Text »    PDF »
The Potential of DNA Vaccination against Tumor-Associated Antigens for Antitumor Therapy.
K. Haupt, M. Roggendorf, and K. Mann (2002)
Experimental Biology and Medicine 227, 227-237
   Abstract »    Full Text »    PDF »
Protective immunity against lethal HSV-1 challenge in mice by nucleic acid-based immunisation with herpes simplex virus type-1 genes specifying glycoproteins gB and gD.
A. BAGHIAN, V. N. CHOULJENKO, O. D'AUVERGNE, M. J. NEWMAN, S. BAGHIAN, and K. G. KOUSOULAS (2002)
J. Med. Microbiol. 51, 350-357
   Abstract »    Full Text »    PDF »
Induction of Long-Term Memory CD8+ T Cells for Recall of Viral Clearing Responses against Influenza Virus.
G. Deliyannis, D. C. Jackson, N. J. Ede, W. Zeng, I. Hourdakis, E. Sakabetis, and L. E. Brown (2002)
J. Virol. 76, 4212-4221
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Induction of Mucosal Protection against Primary, Heterologous Simian Immunodeficiency Virus by a DNA Vaccine.
D. H. Fuller, P. A. Rajakumar, L. A. Wilson, A. M. Trichel, J. T. Fuller, T. Shipley, M. S. Wu, K. Weis, C. R. Rinaldo, J. R. Haynes, et al. (2002)
J. Virol. 76, 3309-3317
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The Magnitude and Specificity of Influenza A Virus-Specific Cytotoxic T-Lymphocyte Responses in Humans Is Related to HLA-A and -B Phenotype.
A. C. M. Boon, G. de Mutsert, Y. M. F. Graus, R. A. M. Fouchier, K. Sintnicolaas, A. D. M. E. Osterhaus, and G. F. Rimmelzwaan (2002)
J. Virol. 76, 582-590
   Abstract »    Full Text »    PDF »
Potent CD4+ T Cell Responses Elicited by a Bicistronic HIV-1 DNA Vaccine Expressing gp120 and GM-CSF.
D. H. Barouch, S. Santra, K. Tenner-Racz, P. Racz, M. J. Kuroda, J. E. Schmitz, S. S. Jackson, M. A. Lifton, D. C. Freed, H. C. Perry, et al. (2002)
J. Immunol. 168, 562-568
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Effects of Antigen and Genetic Adjuvants on Immune Responses to Human Immunodeficiency Virus DNA Vaccines in Mice.
A. C. Moore, W.-p. Kong, B. K. Chakrabarti, and G. J. Nabel (2002)
J. Virol. 76, 243-250
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Protection against Tetanus by Needle-Free Inoculation of Adenovirus-Vectored Nasal and Epicutaneous Vaccines.
Z. Shi, M. Zeng, G. Yang, F. Siegel, L. J. Cain, K. R. van Kampen, C. A. Elmets, and D.-C. C. Tang (2001)
J. Virol. 75, 11474-11482
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Multiple Effects of Codon Usage Optimization on Expression and Immunogenicity of DNA Candidate Vaccines Encoding the Human Immunodeficiency Virus Type 1 Gag Protein.
L. Deml, A. Bojak, S. Steck, M. Graf, J. Wild, R. Schirmbeck, H. Wolf, and R. Wagner (2001)
J. Virol. 75, 10991-11001
   Abstract »    Full Text »    PDF »
CD4+ T Cells Induced by a DNA Vaccine: Immunological Consequences of Epitope-Specific Lysosomal Targeting.
F. Rodriguez, S. Harkins, J. M. Redwine, J. M. de Pereda, and J. L. Whitton (2001)
J. Virol. 75, 10421-10430
   Abstract »    Full Text »    PDF »
Transplacental Genetic Immunization After Intravenous Delivery of Plasmid DNA to Pregnant Mice.
K. Okuda, K.-Q. Xin, A. Haruki, S. Kawamoto, Y. Kojima, F. Hirahara, H. Okada, D. Klinman, and K. Hamajima (2001)
J. Immunol. 167, 5478-5484
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Induction of Immune Response in BALB/c Mice with a DNA Vaccine Encoding Bacterioferritin or P39 of Brucella spp..
A. Al-Mariri, A. Tibor, P. Mertens, X. De Bolle, P. Michel, J. Godfroid, K. Walravens, and J.-J. Letesson (2001)
Infect. Immun. 69, 6264-6270
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Induction of Potent Immune Responses by Cationic Microparticles with Adsorbed Human Immunodeficiency Virus DNA Vaccines.
D. O'Hagan, M. Singh, M. Ugozzoli, C. Wild, S. Barnett, M. Chen, M. Schaefer, B. Doe, G. R. Otten, and J. B. Ulmer (2001)
J. Virol. 75, 9037-9043
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Genetic Immunization with the Region Encoding the {alpha}-Helical Domain of PspA Elicits Protective Immunity against Streptococcus pneumoniae.
J. R. Bosarge, J. M. Watt, D. O. McDaniel, E. Swiatlo, and L. S. McDaniel (2001)
Infect. Immun. 69, 5456-5463
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Two Overlapping Subdominant Epitopes Identified by DNA Immunization Induce Protective CD8+ T-Cell Populations with Differing Cytolytic Activities.
F. Rodriguez, M. K. Slifka, S. Harkins, and J. L. Whitton (2001)
J. Virol. 75, 7399-7409
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Dendritic Cells Can Initiate Protective Immune Responses against Malaria.
O. Bruna-Romero and A. Rodriguez (2001)
Infect. Immun. 69, 5173-5176
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Naked RNA immunization with replicons derived from poliovirus and Semliki Forest virus genomes for the generation of a cytotoxic T cell response against the influenza A virus nucleoprotein.
M. Vignuzzi, S. Gerbaud, S. van der Werf, and N. Escriou (2001)
J. Gen. Virol. 82, 1737-1747
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Mucosal Delivery of Inactivated Influenza Vaccine Induces B-Cell-Dependent Heterosubtypic Cross-Protection against Lethal Influenza A H5N1 Virus Infection.
T. M. Tumpey, M. Renshaw, J. D. Clements, and J. M. Katz (2001)
J. Virol. 75, 5141-5150
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Arg-Gingipain A DNA Vaccine Induces Protective Immunity against Infection by Porphyromonas gingivalis in a Murine Model.
H. Yonezawa, K. Ishihara, and K. Okuda (2001)
Infect. Immun. 69, 2858-2864
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Defined Flanking Spacers and Enhanced Proteolysis Is Essential for Eradication of Established Tumors by an Epitope String DNA Vaccine.
M. P. Velders, S. Weijzen, G. L. Eiben, A. G. Elmishad, P.-M. Kloetzel, T. Higgins, R. B. Ciccarelli, M. Evans, S. Man, L. Smith, et al. (2001)
J. Immunol. 166, 5366-5373
   Abstract »    Full Text »    PDF »
The Potency and Durability of DNA- and Protein-Based Vaccines Against Leishmania major Evaluated Using Low-Dose, Intradermal Challenge.
S. Mendez, S. Gurunathan, S. Kamhawi, Y. Belkaid, M. A. Moga, Y. A. W. Skeiky, A. Campos-Neto, S. Reed, R. A. Seder, and D. Sacks (2001)
J. Immunol. 166, 5122-5128
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Vaccination Strategies for Mucosal Immune Responses.
P. L. Ogra, H. Faden, and R. C. Welliver (2001)
Clin. Microbiol. Rev. 14, 430-445
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Characterization of Hepatitis C Virus Core-Specific Immune Responses Primed in Rhesus Macaques by a Nonclassical ISCOM Vaccine.
N. K. Polakos, D. Drane, J. Cox, P. Ng, M. J. Selby, D. Chien, D. T. O'Hagan, M. Houghton, and X. Paliard (2001)
J. Immunol. 166, 3589-3598
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Antibodies Elicited by Naked DNA Vaccination against the Complementary-determining Region 3 Hypervariable Region of Immunoglobulin Heavy Chain Idiotypic Determinants of B-lymphoproliferative Disorders Specifically React with Patients' Tumor Cells.
M. Rinaldi, F. Ria, P. Parrella, E. Signori, A. Serra, S. A. Ciafrè, I. Vespignani, M. Lazzari, M. G. Farace, G. Saglio, et al. (2001)
Cancer Res. 61, 1555-1562
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Vaccination with Allergen-IL-18 Fusion DNA Protects Against, and Reverses Established, Airway Hyperreactivity in a Murine Asthma Model.
H. T. Maecker, G. Hansen, D. M. Walter, R. H. DeKruyff, S. Levy, and D. T. Umetsu (2001)
J. Immunol. 166, 959-965
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Enhancing B- and T-Cell Immune Response to a Hepatitis C Virus E2 DNA Vaccine by Intramuscular Electrical Gene Transfer.
S. Zucchelli, S. Capone, E. Fattori, A. Folgori, A. Di Marco, D. Casimiro, A. J. Simon, R. Laufer, N. La Monica, R. Cortese, et al. (2000)
J. Virol. 74, 11598-11607
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Protection of Macaca nemestrina from Disease following Pathogenic Simian Immunodeficiency Virus (SIV) Challenge: Utilization of SIV Nucleocapsid Mutant DNA Vaccines with and without an SIV Protein Boost.
R. J. Gorelick, R. E. Benveniste, J. D. Lifson, J. L. Yovandich, W. R. Morton, L. Kuller, B. M. Flynn, B. A. Fisher, J. L. Rossio, M. Piatak Jr., et al. (2000)
J. Virol. 74, 11935-11949
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DNA vaccination: antigen presentation and the induction of immunity.
D. J. Shedlock and D. B. Weiner (2000)
J. Leukoc. Biol. 68, 793-806
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Preventive Effect of Local Plasmid DNA Vaccine Encoding gD or gD-IL-2 on Herpetic Keratitis.
T. Inoue, Y. Inoue, T. Nakamura, A. Yoshida, K. Takahashi, Y. Inoue, Y. Shimomura, Y. Tano, Y. Fujisawa, A. Aono, et al. (2000)
Invest. Ophthalmol. Vis. Sci. 41, 4209-4215
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A Targeted DNA Vaccine Augments the Natural Immune Response to Self TNF-{alpha} and Suppresses Ongoing Adjuvant Arthritis.
G. Wildbaum, S. Youssef, and N. Karin (2000)
J. Immunol. 165, 5860-5866
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Control of Viremia and Prevention of Clinical AIDS in Rhesus Monkeys by Cytokine-Augmented DNA Vaccination.
D. H. Barouch, S. Santra, J. E. Schmitz, M. J. Kuroda, T.-M. Fu, W. Wagner, M. Bilska, A. Craiu, X. X. Zheng, G. R. Krivulka, et al. (2000)
Science 290, 486-492
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Prevention of Adult T-Cell Leukemia-Like Lymphoproliferative Disease in Rats by Adoptively Transferred T Cells from a Donor Immunized with Human T-Cell Leukemia Virus Type 1 Tax-Coding DNA Vaccine.
T. Ohashi, S. Hanabuchi, H. Kato, H. Tateno, F. Takemura, T. Tsukahara, Y. Koya, A. Hasegawa, T. Masuda, and M. Kannagi (2000)
J. Virol. 74, 9610-9616
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Induction of Vigorous Helper and Cytotoxic T Cell as well as B Cell Responses by Dendritic Cells Expressing a Modified Antigen Targeting Receptor-Mediated Internalization Pathway.
Z. You, X. F. Huang, J. Hester, L. Rollins, C. Rooney, and S.-Y. Chen (2000)
J. Immunol. 165, 4581-4591
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Genetic Vaccination against Malaria Infection by Intradermal and Epidermal Injections of a Plasmid Containing the Gene Encoding the Plasmodium berghei Circumsporozoite Protein.
R. Weiss, W. W. Leitner, S. Scheiblhofer, D. Chen, A. Bernhaupt, S. Mostbock, J. Thalhamer, and J. A. Lyon (2000)
Infect. Immun. 68, 5914-5919
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Direct Ex Vivo Kinetic and Phenotypic Analyses of CD8+ T-Cell Responses Induced by DNA Immunization.
D. E. Hassett, M. K. Slifka, J. Zhang, and J. L. Whitton (2000)
J. Virol. 74, 8286-8291
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DNA Vaccines for Influenza Virus: Differential Effects of Maternal Antibody on Immune Responses to Hemagglutinin and Nucleoprotein.
T. M. Pertmer, A. E. Oran, J. M. Moser, C. A. Madorin, and H. L. Robinson (2000)
J. Virol. 74, 7787-7793
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Distribution of DNA Vaccines Determines Their Immunogenicity After Intramuscular Injection in Mice.
M. Dupuis, K. Denis-Mize, C. Woo, C. Goldbeck, M. J. Selby, M. Chen, G. R. Otten, J. B. Ulmer, J. J. Donnelly, G. Ott, et al. (2000)
J. Immunol. 165, 2850-2858
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Evaluation of Hepatitis C Virus Glycoprotein E2 for Vaccine Design: an Endoplasmic Reticulum-Retained Recombinant Protein Is Superior to Secreted Recombinant Protein and DNA-Based Vaccine Candidates.
J. M. Heile, Y.-L. Fong, D. Rosa, K. Berger, G. Saletti, S. Campagnoli, G. Bensi, S. Capo, S. Coates, K. Crawford, et al. (2000)
J. Virol. 74, 6885-6892
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Enhancement of Primary and Secondary Cellular Immune Responses against Human Immunodeficiency Virus Type 1 Gag by Using DNA Expression Vectors That Target Gag Antigen to the Secretory Pathway.
J.-T. Qiu, B. Liu, C. Tian, G. N. Pavlakis, and X.-F. Yu (2000)
J. Virol. 74, 5997-6005
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Human herpesviruses in the cornea.
S. B Kaye, K. Baker, R. Bonshek, H. Maseruka, E. Grinfeld, A. Tullo, D. L Easty, and C. A Hart (2000)
Br. J. Ophthalmol. 84, 563-571
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Induction of AIDS Virus-Specific CTL Activity in Fresh, Unstimulated Peripheral Blood Lymphocytes from Rhesus Macaques Vaccinated with a DNA Prime/Modified Vaccinia Virus Ankara Boost Regimen.
T. M. Allen, T. U. Vogel, D. H. Fuller, B. R. Mothe, S. Steffen, J. E. Boyson, T. Shipley, J. Fuller, T. Hanke, A. Sette, et al. (2000)
J. Immunol. 164, 4968-4978
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Modulation of Antigen-Specific Humoral Responses in Rhesus Macaques by Using Cytokine cDNAs as DNA Vaccine Adjuvants.
J. J. Kim, J.-S. Yang, T. C. VanCott, D. J. Lee, K. H. Manson, M. S. Wyand, J. D. Boyer, K. E. Ugen, and D. B. Weiner (2000)
J. Virol. 74, 3427-3429
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Enhancement of Immunoglobulin G2a and Cytotoxic T-Lymphocyte Responses by a Booster Immunization with Recombinant Hepatitis C Virus E2 Protein in E2 DNA-Primed Mice.
M. K. Song, S. W. Lee, Y. S. Suh, K. J. Lee, and Y. C. Sung (2000)
J. Virol. 74, 2920-2925
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