Granted Patent
B2
US 12,233,117 · App. 18/359,740 · Granted Feb 25, 2025
Immunogenic compositions, antigen screening methods, and methods of generating immune responses
Assignee:
UNIVERSITY OF WASHINGTON
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Abstract
An immunogenic composition is provided herein. The immunogenic compositions are used to identify and select immunogenic antigens that elicit immune responses in a subject and may be subsequently used in multi-antigen vaccine compositions against one or more diseases or conditions. According to some embodiments, the immunogenic composition may include a plurality of nucleic acid fragments or minigenes derived from a nucleic acid library, wherein each nucleic acid fragment encodes a different antigen or functional portion thereof, and wherein the different antigens or functional portions thereof are associated with one or more disease or condition. The immunogenic composition may also include a delivery medium loaded with the plurality of nucleic acid fragments and in some embodiments, the delivery medium is loaded with nucleic acid fragments in such a way that individual antigen presenting cells receive only a subset of the nucleic acids within a vaccine in order to minimize antigenic competition.
Claims (16)
1. An immunogenic composition comprising:
two or more plasmid pools, including a first plasmid pool and a second plasmid pool;
where at least the first plasmid pool is loaded onto or into a first aliquot of gold beads and where at least the second plasmid pool is loaded onto or into a second aliquot of gold beads;
where each of the first and the second aliquots of gold beads are loaded into a dosing container;
where the first plasmid pool comprises a first plurality of plasmids and where the second plasmid pool comprises a second plurality of plasmids different from the first plurality of plasmids;
where each plasmid in the two or more plasmid pools contains a minigene encoding an epitope or functional portion thereof from one or more proteins; and
where at least the first and the second plasmid pools in the dosing container together contain more than one of the minigenes that encode the epitope or functional portion thereof.
2. An immunogenic composition comprising:
two or more minigene pools, including a first minigene pool and a second minigene pool;
where at least the first minigene pool is loaded onto or into a first aliquot of gold beads and where at least the second minigene pool is separately loaded onto or into a second aliquot of gold beads;
where each of the first and the second aliquots of gold beads are loaded into a dosing container;
where the first minigene pool comprises a first plurality of minigenes and where the second minigene pool comprises a second plurality of minigenes different from the first plurality of minigenes; and
where each of the first plurality of minigenes encode an antigen or functional portion thereof from a first protein, and where each of the second plurality of minigenes encode an antigen or functional portion thereof from a second protein.
3. The immunogenic composition of claim 1 , wherein each two or more plasmid pools comprise two or more different minigenes.
4. The immunogenic composition of claim 3 , wherein the epitope or functional portion thereof encoded by each two or more different minigenes targets a different antigen on the same protein.
5. The immunogenic composition of claim 3 , wherein the epitope or functional portion thereof encoded by each two or more different minigenes targets a different antigen on different proteins.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Oct 10, 2023
From: MURPHY, SEAN C.; STONE, BRAD
To: UNIVERSITY OF WASHINGTON
Reel/Frame 065175/0906 →
Continuity (4)
Continuation
15749928
Provisional Application
62200487
· Aug 3, 2015
References Cited (117)
US 7253333B2
· Tanaka et al.
· 2007
[cited by applicant]
US 20030157534A1
· Engelhorn et al.
· 2003
[cited by applicant]
US 20050208078A1
· Hoffman et al.
· 2005
[cited by applicant]
US 20060051348A1
· Gorlach et al.
· 2006
[cited by applicant]
US 20060094649A1
· Keogh et al.
· 2006
[cited by applicant]
US 20090274726A1
· Brett et al.
· 2009
[cited by applicant]
US 20110184160A1
· Weiner et al.
· 2011
[cited by applicant]
WO 9631613A1
· 1996
[cited by applicant]
WO 9941383A1
· 1999
[cited by applicant]
WO 2005025614A2
· 2005
[cited by applicant]
Aguiar, JC, et al. “Discovery of Novel Plasmodium falciparum Pre-Erythrocytic Antigens for Vaccine Development” PLoS One, Aug. 20, 2015, 10(8). 24 pages.
[cited by applicant]
Arrington, J. et al. “Plasmid Vectors Encoding Cholera Toxin or the Heat-Labile Enterotoxin from
[cited by applicant]
Barry, M. et al. “Expression library immunization to discover and improve vaccine antigens” Immunological Reviews, 2004, vol. 199, pp. 68-83.
[cited by applicant]
Barth, S. et al. “Autophagy: Assays and Artifacts” Journal of Pathology, Jun. 2010, 221(2) pp. 117-124.
[cited by applicant]
Bergmann-Leitner, Elke S et al. “Immunization with Pre-Erythrocytic Antigen CelTOS from Plasmodium Falciparum Elicits Cross-Species Protection against Heterologous Challenge with Plasmodium Berghei.” PLoS One, Aug. 2010…
[cited by applicant]
Braeckel-Budimir et al. “Highly focused TCR Vβ repertoire is associated with a large number of naive precursors and robust CD8 T cell responses specific for a Plasmodium antigen” Journal of Immunology, May 2015, vol. 19…
[cited by applicant]
Braeckel-Budimir, N. et al. “CD8T-cell-mediated protection against liver-stage malaria: lessons from a mouse model” Frontiers in Microbiology, Jun. 2014, vol. 5, 9 pages.
[cited by applicant]
Canakoglu, Nurettin et al. “Immunization of Knock-Out A/β Interferon Receptor Mice against High Lethal Dose of Crimean-Congo Hemorrhagic Fever Virus with a Cell Culture Based Vaccine.” PLoS Neglected Tropical Diseases, …
[cited by applicant]
Cardile, AP, et al. Monitoring Exposure to Ebola and Health of U.S. Military Personnel Deployed in Support of Ebola Control Efforts—Liberia, Oct. 25, 2014-Feb. 27, 2015. MMWR Morbidity and Mortality Weekly Report. 2015;…
[cited by applicant]
De Filette, Marina et al. “Vaccination of Mice Using the West Nile Virus E-Protein in a DNA Prime-Protein Boost Strategy Stimulates Cell-Mediated Immunity and Protects Mice against a Lethal Challenge.” PLoS One, Feb. 20…
[cited by applicant]
Dobano, C et al. “Targeting antigen to MHC Class I and Class II antigen presentation pathways for malaria DNA vaccines” Immunology Letters, 2007, vol. 111, pp. 92-102.
[cited by applicant]
Doll, K. et al. “Protective capacity of CD8 T cells targeting a spectrum of Plasmodium-specific epitopes (MPF6P.735)” Journal of Immunology, May 2014, vol. 192, Supplement 1, 5 pages.
[cited by applicant]
Doolan, D. et al. “Circumventing genetic restriction of protection against malaria with multigene DNA immunization: CD8+ cell-, interferon gamma-, and nitric oxide-dependent immunity” Journal of Experimental Medicine, 1…
[cited by applicant]
Doolan, D. et al. “Identification of Plasmodium falciparum antigens by antigenic analysis of genomic and proteomic data.” Proc Natl Acad Sci USA. Aug. 19, 2003, 100(17) pp. 9952-9957.
[cited by applicant]
Doolan, D. et al. “The Complexity of Protective Immunity Against Liver-Stage Malaria” J Immunol Aug. 1, 2000, 165 (3) pp. 1453-1462.
[cited by applicant]
Duffy, P. et al. “Pre-erythrocytic malaria vaccines: identifying the targets” Expert Rev Vaccines. Oct. 2012;11(10):pp. 1261-1280.
[cited by applicant]
Dunachie, S.J. et al. “A DNA Prime-Modified Vaccinia Virus Ankara Boost Vaccine Encoding Thrombospondin-Related Adhesion Protein but Not . . . ” Infection and Immunity, Oct. 2006, 74(10), pp. 5933-5942.
[cited by applicant]
Epstein, J.E. et al. “Live Attenuated Malaria Vaccine Designed to Protect Through Hepatic CD8+ T Cell Immunity” Science, Oct. 28, 2011, vol. 334; pp. 475-480.
[cited by applicant]
Fan, Y. et al. “B7-DC-silenced dendritic cells induce stronger anti-HBV immunity in transgenic mice” Archives of Virology, 2009, vol. 154, pp. 1813-1821.
[cited by applicant]
Ferraro, B., et al. “Inducing humoral and cellular responses to multiple sporozoite and liver-stage malaria antigens using exogenous plasmid DNA” Infect Immun. Oct. 2013; 81(10):pp. 3709-3720.
[cited by applicant]
Fidock, D. et al. “Cloning and characterization of a novel Plasmodium falciparum sporozoite surface antigen, STARP” Molecular and Biochemical Parasitology, 1994, vol. 64, pp. 219-232.
[cited by applicant]
Frevert, U. et al. “Plasmodium cellular effector mechanisms and the hepatic microenvironment” Frontiers in Microbiology, May 27, 2015; vol. 6; 19 pages.
[cited by applicant]
Friedrich, TC et al. “Subdominant CD8+ T-cell responses are involved in durable control of AIDS virus replication” J. Virology; Apr. 2007; 81(7); pp. 3465-3476.
[cited by applicant]
From the Centers for Disease Control and Prevention, “Dengue fever among U.S. military personnel—Haiti, Sep.-Nov. 1994” JAMA, 1995, vol. 273, No. 1, pp. 14-15.
[cited by applicant]
Fu, T-M. et al. “Induction of MHC class I-restricted CTL response by DNA immunization with ubiquitin-influenza virus nucleoprotein fusion antigens” Vaccine, 1998, vol. 16, No. 18, pp. 1711-1717.
[cited by applicant]
Fuller, D. et al. “Therapeutic DNA Vaccine Induces Broad T Cell Responses in the Gut and Sustained Protection from Viral Rebound and AIDS in SIV-Infected Rhesus Macaques”
[cited by applicant]
Gibbons, RV. et al. “Dengue and US military operations from the Spanish-American War through today” Emerg Infect Dis. Apr. 2012;18(4) pp. 623-630.
[cited by applicant]
Goicochea, MA et al. “Evaluation of Lassa virus vaccine immunogenicity in a CBA/J-ML29 mouse model” Vaccine. Feb. 14, 2012; 30(8): pp. 1445-1452.
[cited by applicant]
Goldwich, A. et al. “Targeting HIV-1 Gag into the Defective Ribosomal Product Pathway Enhances MHC Class I Antigen Presentation and CD8+ T Cell Activation” J Immunol; Jan. 1, 2008, 180(1) pp. 372-382.
[cited by applicant]
Guerin-Marchand, C. et al. “A Liver-stage-specific antigen of Plasmodium falciparum characterized by gene cloning” Nature, Sep. 1987, vol. 329, pp. 164-167.
[cited by applicant]
Guo, H. et al. “Immunodominant Epitopes Mapped by Synthetic Peptides on the Capsid Protein of Avian Hepatitis E Virus Are Non-Protective” Viral Immunology, 2008, vol. 21, No. 1, pp. 61-67.
[cited by applicant]
Hassan, I. A. et al. “Immunological response and protection of mice immunized with plasmid encoding Toxoplasma gondii glycolytic enzyme malate dehydrogenase” Parasite Immunology, 2014, vol. 36, pp. 674-683.
[cited by applicant]
Hiller, N. et al. “A Host-Targeting Signal in Virulence Proteins Reveals a Secretome in Malarial Infection”Science, Dec. 10, 2004; 306(5703); pp. 1934-1937.
[cited by applicant]
Hoffman, SL. et al. “The march toward malaria vaccines” Vaccine. Nov. 27, 2015;33 Suppl 4:D13-23.
[cited by applicant]
Hoffmann, SL. et al. “The march towards malaria vaccines” Am J Prev Med. Dec. 2015;49(6 Suppl 4):S319-33.
[cited by applicant]
Hondowicz, B. et al. “Discovery of T Cell Antigens by High-Throuput Screening of Synthetic Minigene Libraries” PLoS One, 2012, 7(1). 10 pages.
[cited by applicant]
Hooper, JW et al. “DNA Vaccination with Vaccinia Virus L1R and A33R Genes Protects Mice against a Lethal Poxvirus Challenge” Virology. Jan. 20, 2000;266(2):329-39.
[cited by applicant]
Hooper, JW. et al. “Four-gene-combination DNA vaccine protects mice against a lethal vaccinia virus challenge and elicits appropriate antibody responses in nonhuman primates” Virology, 2003, vol. 306, pp. 181-195.
[cited by applicant]
Hospers, G. et al. “Construction of a triple modified p53 containing DNA vaccine to enhance processing and presentation of the p53 antigen” Vaccine 2010, vol. 28, pp. 386-391.
[cited by applicant]
Im, E-J. et al. “Protective Efficacy of Serially Up-Ranked Subdominant CD8+ T Cell Epitopes against Virus Challenges” PLoS Pathogens, May 2011, vol. 7, Issue 5, 13 pages.
[cited by applicant]
Imai, T. et al. “tigen-specific CD8+ T cells induced by the ubiquitin fusion degradation pathway” Biochemical and Biophysical Research Communications 365 (2008) 758-763.
[cited by applicant]
ISA/US, “International Search Report and Written Opinion”, for PCT/US16/45439, 8 pgs, Oct. 18, 2016.
[cited by applicant]
Kariu, T. et al. “CelTOS, a novel malarial protein that mediates transmission to mosquito and vertebrate hosts” Molecular Microbiology, 2006, vol. 59, pp. 1369-1379.
[cited by applicant]
Keitany, G. et al. “Immunization of Mice with Live-Attenuated Late Liver Stage-Arresting Plasmodium yoelii Parasites Generates Protective Antibody Responses to Preerythrocytic Stages of Malaria” Infection & Immunity, De…
[cited by applicant]
Khusmith, S. et al. “Protection Against Malaria by Vaccination with Sporozoite Surface Protein 2 Plus CS Protein” Science, New Series, vol. 252, No. 5006 (May 3, 1991), pp. 715-718.
[cited by applicant]
Kumar, S. et al. “Cytotoxic T cells specific for the circumsporozoite protein of Plasmodium falciparum” Nature, Jul. 1988, vol. 334, pp. 258-260.
[cited by applicant]
Kunwar, R. et al. “Dengue outbreak in a large military station: Have we learnt any lesson?” Medical Journal Armed Forces India, 2015, vol. 71, pp. 11-14.
[cited by applicant]
La Motte, R. et al. “Importance of B7-1-Expressing Host Antigen-Presenting Cells for the Eradication of B7-2 Transfected P815 Tumor Cells” J. Immunol, 1998, vol. 161, pp. 6552-6558.
[cited by applicant]
Lauer, P. et al. “Construction, Characterization, and Use of Two Listeria monocytogenes Site-Specific Phage Integration Vectors” Journal of Bacteriology, Aug. 2002, vol. 184, No. 15, pp. 4177-4186.
[cited by applicant]
Liu J, et al. “Enhancing Virus-Specific Immunity In Vivo by Combining Therapeutic Vaccination and PD-L1 Blockade in Chronic Hepadnaviral Infection” PLoS Pathogens, 2014 10(1): 14 pages.
[cited by applicant]
Liu, J. et al. “Modulation of DNA Vaccine-Elicited CD8 T-Lymphocyte Epitope Immunodominance Hierarchies” Journal of Virolology, Dec. 2006, vol. 80, No. 24, pp. 11991-11997.
[cited by applicant]
Luke, J. et al. “Improved antibiotic-free DNA vaccine vectors utilizing a novel RNA based plasmid selection system” published in Vaccine, Oct. 2009, vol. 27, No. 46. Author manuscript. 16 pages.
[cited by applicant]
Lundegaard, C. “NetMHC-3.0: accurate web accessible predictions of human, mouse and monkey MHC class I affinities for peptides of length 8-11” Nucleic Acids Research, 2008, vol. 36. W509-W512.
[cited by applicant]
Marti, M. et al. “Targeting Malaria Virulence and Remodeling Proteins to the Host Erythrocyte” Science, Dec. 2004, vol. 306, pp. 1930-1933.
[cited by applicant]
Mishra, S. et al. “Identification of non-CSP antigens bearing CD8 epitopes in mice immunized with irradiated sporozoites” Vaccine, Oct. 2011, vol. 29, No. 43, pp. 7335-7342.
[cited by applicant]
Moelans, I. et al. “A novel protein antigen of the malaria parasite Plasmodium falciparum, located on the surface of gametes and sporozoites” Molecular and Biochemical Parasitology, 1991, vol. 45, pp. 193-204.
[cited by applicant]
Moorthy, V.S., et al. “Safety of DNA and modified vaccinia virus Ankara vaccines against liver-stage P. falciparum malaria in non-immune volunteers” Vaccine 21 (2003) pp. 1995-2002.
[cited by applicant]
Mueller, A-K. et al. “Genetically modified Plasmodium parasites as a protective experimental malaria vaccine” Nature, Jan. 2005, vol. 433, pp. 164-167 with additional Corrections & Amendments page.
[cited by applicant]
Mullbacher, A. et al. Alloreactive Cytotoxic T-Cell Function, Peptide Nonspecific Scand. J. Immunol. 1999, vol. 49, pp. 563-569.
[cited by applicant]
Murphy, S. et al. “A T-cell response to a liver-stage Plasmodium antigen is not boosted by repeated sporozoite immunizations” PNAS, Apr. 2013, vol. 110, No. 15, pp. 6055-6060.
[cited by applicant]
Nagata, L. et al. “Efficacy of DNA vaccination against western equine encephalitis virus infection” Vaccine 23 (2005) pp. 2280-2283.
[cited by applicant]
Novotny, L. et al. “The Fourth Surface-Exposed Region of the Outer Membrane Protein P5-Homologous Adhesin of Nontypable Haemophilus influenza Is an Immunodominant But Nonprotective Decoying Epitope” J. Immunol., 2003, v…
[cited by applicant]
Nussenzweig, R.S. et al. “Protective Immunity produced by the Injection of X-irradiated Sporozoites of Plasmodium berghei” Nature, Oct. 1967, vol. 216. pp. 160-162.
[cited by applicant]
Peng, S. et al. “Cluster intradermal DNA vaccination rapidly induces E7-specific CD8+ T-cell immune responses leading to therapeutic antitumor effects” Gene Therapy (2008) 15, pp. 1156-1166.
[cited by applicant]
Pertmer, T. et al. “Gene gun-based nucleic acid immunization: elicitation of humoral and cytotoxic T lymphocyte responses following epidermal delivery of nanogram quantities of DNA” Vaccine, 1995, vol. 13, No. 15, pp. 1…
[cited by applicant]
Pinto, A. et al. “Defining New Therapeutics Using a More Immunocompetent Mouse Model of Antibody-Enhanced Dengue Virus Infection” MBio, Sep./Oct. 2015, vol. 6, Issue 5, 13 pages.
[cited by applicant]
Putrianti, E. et al. “Vaccine-like Immunity against Malaria by Repeated Causal-Prophylactic Treatment of Liver-Stage Plasmodium Parasites” The Journal of Infectious Diseases, vol. 199, No. 6 (Mar. 15, 2009), pp. 899-903.
[cited by applicant]
Reed, D. et al. “Combined Alphavirus Replicon Particle Vaccine Induces Durable and Cross-Protective Immune Responses against Equine Encephalitis Viruses” Journal of Virology, Oct. 2014, vol. 88, No. 20. pp. 12077-12086.
[cited by applicant]
Reguzova, A. et al. “Design and Evaluation of Optimized Artificial HIV-1 Poly-T Cell-Epitope Immunogens” PLoS One, Mar. 2015, 18 pages.
[cited by applicant]
Reisler, R. et al. “Immune interference in the setting of same-day administration of two similar inactivated alphavirus vaccines: Eastern equine and western equine encephalitis” Vaccine 30 (2012) pp. 7271-7277.
[cited by applicant]
Richie, T. et al. “Clinical trial in healthy malaria-naïve adults to evaluate the safety, tolerability, immunogenicity and efficacy of MustDO5 . . . ” Human Vaccines & Immunotherapeutics, Nov. 2012, 8(11), pp. 1564-1584.
[cited by applicant]
Robson, K. et al. “A highly conserved amino-acid sequence in thrombospondin, properdin and in proteins from sporozoites and blood stages of a human malaria parasite” Nature, Sep. 1988, vol. 335, pp. 79-82.
[cited by applicant]
Rodriguez, F. et al. “Immunodominance in Virus-Induced CD8 T-Cell Responses Is Dramatically Modified by DNA Immunization and Is Regulated by Gamma Interferon” Journal of Virology, May 2002, vol. 76, No. 9 p. 4251-4259.
[cited by applicant]
Roestenberg, M. et al. “Protection against a Malaria Challenge by Sporozoite Inoculation” New England Journal of Medicine, 2009, vol. 361, pp. 468-477.
[cited by applicant]
Ruckwardt, T. et al. “Responses against a Subdominant CD8+ T Cell Epitope Protect against Immunopathology Caused by a Dominant Epitope” Journal of Immunology, 2010, vol. 185, pp. 4673-4680.
[cited by applicant]
Sanchez, G. et al. “Plasmodium falciparum: Exported Protein-1, a Blood Stage Antigen, is Expressed in Liver Stage Parasites” Experimental Parasitology, 1994, vol. 79, pp. 59-62.
[cited by applicant]
Schmidt, N. et al. “Extreme CD8 T Cell Requirements for Anti-Malarial Liver-Stage Immunity following Immunization with Radiation Attenuated Sporozoites” PloS Pathogens, Jul. 2010, vol. 6, No. 7, 15 pages.
[cited by applicant]
Schmidt, N. et al. “Memory CD8 T cell responses exceeding a large but definable threshold provide long-term immunity to malaria” PNAS, Sep. 2008, vol. 105, No. 37, pp. 14017-14022.
[cited by applicant]
Schwartz, J. et al. “Accurate gene synthesis with tag-directed retrieval of sequence-verified DNA molecules” Nature Methods, Sep. 2012, vol. 9, No. 9, pp. 913-915 with two supplemental pages.
[cited by applicant]
Sedegah, M. “Sterile Immunity to Malaria after DNA Prime/Adenovirus Boost Immunization Is Associated with Effector Memory CD8+T Cells Targeting AMA1 Class I Epitopes” PLoS One, Sep. 2014, vol. 9, No. 9, 19 pages.
[cited by applicant]
Sedegah, M. et al. “Effect on antibody and T-cell responses of mixing five GMP-produced DNA plasmids and administration with plasmid expressing GM-CSF” Genes and Immunity (2004) vol. 5, pp. 553-561.
[cited by applicant]
Sedegah, M. et al. “Protection against malaria by immunization with plasmid DNA encoding circumsporozoite protein” Proc. Natl. Acad. Sci. USA, Oct. 1994, vol. 91, pp. 9866-9870.
[cited by applicant]
Seder, R. et al. “Protection against Malaria by Intravenous Immunization with a Nonreplicating Sporozoite Vaccine” Science, Sep. 2013, vol. 341, pp. 1359-1365.
[cited by applicant]
Seidlein, L. et al. “Malaria vaccines: past, present and future” Arch Dis Child 2013;98:981-985.
[cited by applicant]
Spring, M. et al. “First-in-human evaluation of genetically attenuated Plasmodium falciparum sporozoites administered by bite of Anopheles mosquitoes to adult volunteers” Vaccine, 2013, vol. 31, pp. 4975-4983.
[cited by applicant]
Steitz, J. et al. “Biolistic DNA vaccination against melanoma” Biolistic DNA Delivery, Springer; 2013. p. 317-337.
[cited by applicant]
Stoute, J. et al. “A Preliminary Evaluation of a Recombinant Circumsporozoite Protein Vaccine against Plasmodium Falciparum Malaria” New England Journal of Medicine, Jan. 1997, pp. 86-91.
[cited by applicant]
Trofa, A. et al. “Dengue Fever in US Military Personnel in Haiti” JAMA, May 1997, vol. 277, No. 19, pp. 1546-1548.
[cited by applicant]
Tsuda, Y. et al. “A cytomegalovirus-based vaccine provides long-lasting protection against lethal Ebola virus challenge after a single dose” Vaccine, 2015, vol. 33, pp. 2261-2266.
[cited by applicant]
Van Der Most, R. et al. “Analysis of Cytotoxic T Cell Responses to Dominant and Subdominant Epitopes During Acute and Chronic Lymphocytic Choriomeningitis Virus Infection” J Immunol 1996; 157, pp. 5543-5554.
[cited by applicant]
Van der Most, R. et al. “Identification of Db- and Kb-Restricted Subdominant Cytotoxic T-Cell Responses in Lymphocytic Choriomeningitis Virus-Infected Mice” Virology, 1998, vol. 240, pp. 158-167.
[cited by applicant]
Vaughan, A. et al. “Type II fatty acid synthesis is essential only for malaria parasite late liver stage development” Cellular Microbiology (2009) 11(3), 506-520.
[cited by applicant]
Wang, R. “Simultaneous Induction of Multiple Antigen-Specific Cytotoxic T Lymphocytes in Nonhuman Primates by Immunization with a Mixture of Four Plasmodium falciparum DNA Plasmids” Infection and Immunity, Sep. 1998, pp…
[cited by applicant]
Wang, R. et al. “Boosting of DNA Vaccine-Elicited Gamma Interferon Responses in Humans by Exposure to Malaria Parasites” Infection and Immunity, May 2005, vol. 73, No. 5, pp. 2863-2872.
[cited by applicant]
Wang, R. et al. “Induction of Antigen-Specific Cytotoxic T Lymphocytes in Humans by a Malaria DNA Vaccine” Science, Oct. 1998, vol. 282, pp. 476-480.
[cited by applicant]
Warfield, K. et al. “Development and Characterization of a Mouse Model for Marburg Hemorrhagic Fever” Journal of Virology, Jul. 2009, pp. 6404-6415.
[cited by applicant]
Weiss, W. et al. “Cytotoxic T Cells recognize a peptide from the circumsporozoite protein on malartia-infected hepatocytes” Journal of Experimental Medicine, Mar. 1990, vol. 171, pp. 763-773.
[cited by applicant]
Weiss, W. et al. “Protective CE8+ T lymphocytes in Primates Immunized with Malaria Sporozoites” PLoS One, Feb. 2012, 4 pages.
[cited by applicant]
Who, “Global Malaria Programme: World Malaria Report 2014” 2014, 142 pages.
[cited by applicant]
Wick, D. et al. “Profound CD8+ T cell immunity elicited by sequential daily immunization with exogenous antigen plus the TLR3 agonist poly(I:C)” Vaccine, 2011, vol. 29, pp. 984-993.
[cited by applicant]
Williams, J. “Improving DNA Vaccine Performance Through Vector Design” Current Gene Therapy, Aug. 2014, vol. 14, No. 3, 21 pages.
[cited by applicant]
Yager, E. et al. “Particle-mediated DNA vaccines against seasonal and pandemic influenza viruses elicit strong mucosal antibody and T cell responses in the lung” Procedia in Vaccinology 3 (2010) 2-11.
[cited by applicant]
Zhang, Y. et al. “Seamless Ligation Cloning Extract (SLiCE) Cloning Method” Methods Mol Biol. 2014 ; 1116: 235-244.
[cited by applicant]
Zhu, J. et al. “Structure of Plasmodium falciparum liver stage antigen-1” Molecular and Biochemical Parasitology, 1991, vol. 48, pp. 223-226.
[cited by applicant]