Stephen L. Hoffman

Changes in the total leukocyte and platelet counts in Papuan and non Papuan adults from northeast Papua infected with acute Plasmodium vivaxor uncomplicated Plasmodium falciparummalaria (2008)

Taylor, Walter RJ, Widjaja, Hendra, Basri, Hasan, Ohrt, Colin, Tjitra, Emiliana, ...

Abstract Background There are limited data on the evolution of the leukocyte and platelet counts in malaria patients. Methods In a clinical trial of chloroquine vs. chloroquine plus doxycycline vs....

High-Throughput Generation of P. falciparum Functional Molecules by Recombinational Cloning (2007)

Aguiar, Joao C., LaBaer, Joshua, Blair, Peter L., Shamailova, Victoria Y., Koundinya, Malvika, Russell, Joshua A., ...

Large-scale functional genomics studies for malaria vaccine and drug development will depend on the generation of molecular tools to study protein expression. We examined the feasibility of a...

Preventing Malaria: Part 2 of Somalia and General Slim (2006)

Crutcher, James M., Sharp, Trueman W., Wallace, Mark R., Hoffman, Stephen L.

If mosquitoes can't bite you, you can't get malaria. Table 1 shows the methods of protection from biting insects. These methods will also protect against many other mosquito-borne diseases, such as...

Inducing Protective Immune Responses Against the Sporozoite and Liver Stages of Plasmodium (2006)

Hoffman, Stephen L., Franke, Eileen D.

Work on vaccines against the pre-erythrocytic stages of the Plasmodium life cycle is based on the observation that immunization with irradiated sporozoites (IRR SPZ) is protective. Antibodies against...

Complete Protection against Plasmodium Yoelii by Adoptive Transfer of a CD8+ Cytotoxic T-Cell Recognizing Sporozoite Surface Protein 2 (2006)

Khusmith, Srisin, Sedegah, Martha, Hoffman, Stephen L.

BALB/c mice immunized with irradiated Plasmodium yoelii sporozoites produce antibodies and cytotoxic T lymphocytes against the circumsporozoite protein and against a 140-kDa protein, sporozoite...

Cytotoxic T Lymphocytes in Humans Exposed to Plasmodium Falciparum by Immunization or Natural Exposure (2006)

Malik, A., Sedegah, Martha, Hoffman, Stephen L.

Malaria is one of the most important infectious diseases in the world. It is estimated that 2.1 billion people live in areas of the world where malaria is transmitted and that there are 100-300...

Malaria Transmission Dynamics at a Site in Northern Ghana Proposed for Testing Malaria Vaccines (2006)

Appawu, Maxwell, Owusu-Agyel, Seth, Dadzie, Samuel, Asoala, Victor, Anto, Franis, Koram, Kwadwo, ...

We studied the malaria transmission dynamics in Kassena Nankana district (KND), a site in northern Ghana proposed for testing malaria vaccines. Intensive mosquito sampling for 1 year using human...

Protection Against Malaria by Immunization with Plasmid DNA Encoding Circumsporozoite Protein (2006)

Sedegah, Martha M., Hedstrom, Richard, Hobart, Peter, Hoffman, Stephen L.

Immunization with irradiated sporozoites protects animals and humans against malaria, and the circumsporozoite protein is a target of this protective immunity. We now report that adjuvant-free...

CpG Oligodeoxynucleotide and Montanide ISA 51 Adjuvant Combination Enhanced the Protective Efficacy of a Subunit Malaria Vaccine (2006)

Kumar, Sanjai, Jones, Trevor R., Oakley, Miranda S., Zheng, Hong, Kuppusamy, Shanmuga P., Taye, Alem, ...

Unmethylated CpG dinucleotide motifs present in bacterial genomes or synthetic oligodeoxynucleotides (ODNs) serve as strong immunostimulatory agents in mice, monkeys and humans. We determined the...

Streptokinase Clot Culture Compared with Whole Blood Culture for Isolation of Salmonella typhi and S. Paratyphi A from Patients with Enteric Fever (2005)

Simajuntak, Cyrus H., Hoffman, Stephen L., Darmowigoto, Ruwido, Lesmana, Murad, Edman, Soeprawoto

The sensitivities of whole blood and clot cultures were compared in 155 patients with typhoid or paratyphoid fever. Salmonella typhi or s. paratyphi A were isolated from 98.7% of 5 ml 1:10...

Molecular dissection of the human antibody response to the structural repeat epitope of Plasmodium falciparumsporozoite from a protected donor (2004)

Chappel, Jonathan A, Rogers, William O, Hoffman, Stephen L, Kang, Angray S

Abstract Background The circumsporozoite surface protein is the primary target of human antibodies against Plasmodium falciparum sporozoites, these antibodies are predominantly directed to the major...

Induction in Humans of CD8+ and CD4+ T Cell and Antibody Responses by Sequential Immunization with Malaria DNA and Recombinant Protein (2004)

Wang, Ruobing, Epstein, Judith, Charoenvit, Yupin, Baraceros, Fe Maria, Rahardjo, Nancy, Gay, Tanya, ...

Vaccine-induced protection against diseases like malaria, AIDS, and cancer may require induction of Ag-specific CD8+ and CD4+ T cell and Ab responses in the same individual. In humans, a recombinant...

High-Throughput Generation of P. falciparum Functional Molecules by Recombinational Cloning (2004)

Aguiar, João Carlos, LaBaer, Joshua, Blair, Peter L., Shamailova, Victoria Y., Koundinya, Malvika, Russell, Joshua A., ...

Large-scale functional genomics studies for malaria vaccine and drug development will depend on the generation of molecular tools to study protein expression. We examined the feasibility of a...

Persistence of Protective Immunity to Malaria Induced by DNA Priming and Poxvirus Boosting: Characterization of Effector and Memory CD8+-T-Cell Populations (2002)

Sedegah, Martha, Brice, Gary T., Rogers, William O., Doolan, Denise L., Charoenvit, Yupin, Jones, Trevor R., ...

The persistence of immunity to malaria induced in mice by a heterologous DNA priming and poxvirus boosting regimen was characterized. Mice were immunized by priming with DNA vaccine plasmids encoding...

Emotional Intelligence: A Look at Its Effect on Performance at the United States Naval Academy. (1999)

Hoffman, Stephen L.

This study uses the results from the BarOn Emotional Quotient (BQ) Inventory by a freshman class upon entry to the United States Naval Academy. The data reflects the response of 1,040 students...

Immunogenicity and in vitro protective efficacy of a recombinant multistage Plasmodium falciparum candidate vaccine. (1999)

Shi, Ya Ping, Hasnain, Seyed E., Sacci, John B., Holloway, Brian P., Fujioka, Hisashi, Kumar, Nirbhay, ...

Compared with a single-stage antigen-based vaccine, a multistage and multivalent Plasmodium falciparum vaccine would be more efficacious by inducing "multiple layers" of immunity. We have constructed...

Characterization of the Gene Encoding Sporozoite Surface Protein 2, a Protective Plasmodium yoelii Sporozoite Antigen. (1998)

Rogers, William O., Rogers, Miriam D., Hedstrom, Richard C., Hoffman, Stephen L.

Sporozoite surface protein 2 (SSP2) is a 140-kDa, protective sporozoite surface protein from Plasmodium yoelii distinct from the circumsporozoite protein (CSP). A genomic clone containing the SSP2...

Molecular Dissection of the Human Antibody Response to the Structural Repeat Epitope of Plasmodium falciparum sporozoite from a Protected Donor (1998)

Chappel, Jonathan A., Rogers, William O., Hoffman, Stephen L., Kang, Angray S.

The circumsporozoite surface protein is the primary target of human antibodies against Plasmodium falciparum sporozoites, these antibodies are predominantly directed to the major repetitive epitope...

Protective Four Amino Acid Epitope Against Plasmodium vivax Malaria. (1998)

Hoffman, Stephen L., Charoenvit, Yupin, Jones, Trevor T.

A synthetic peptide of the human malaria Plasmodium vivax, containing at least one repeat of a synthetic peptide having the amino acid sequence Ala-Gly-Asp-Arg (AGDR) which is a protective epitope...

Protective Malaria Sporozoite Surface Protein Immunogen and Gene. (1998)

Hoffman, Stephen L., Charoenvit, Yupin, Hedstrom, Richard, Khusmith, Srisin

A protein antigen (SSP2) on the surface of Plasmodium sporozoites is disclosed as a candidate immunogen for vaccination against malaria. This use of this protein, which is distinct from the...

Recombinant Leishmania Containing Genes Encoding Proteins From Infectious Disease Agents and Method of Inducting Cellular Immune Response. (1998)

Rogers, William O., Hoffman, Stephen L.

This invention relates to recombinant strains of Leishmania which express foreign proteins, useful for vaccination against infectious diseases. More particularly, this invention relates to strains of...

Immunogenic Four Amino Acid Epitope against Plasmodium Vivax. (1998)

Hoffman, Stephen L., Charoenvit, Yupin, Jones, Trevor R.

An agent and pharmaceutical formulations of the agent containing a synthetic peptide of the human malaria Plasmodium vivax, containing at least one repeat of a synthetic peptide having the amino acid...

Dose- and Time-dependent Relations between Infective Anopheles Inoculation and Outcomes of Plasmodium falciparum Parasitemia among Children in Western Kenya (1997)

McElroy, Peter D., Beier, John C., Oster, Charles N., Onyango, Fred K., Oloo, Aggrey J., Lin, Xihong, ...

Blood-stage level Plasmodium falciparum infection (parasitemia density) is generally elevated prior to, or at the time of, clinical presentation of severe pediatric malaria episodes. Intensity of...

THE WIDAL SLIDE AGGLUTINATION TEST, A VALUABLE RAPID DIAGNOSTIC TEST IN TYPHOID FEVER PATIENTS AT THE INFECTIOUS DISEASES HOSPITAL OF JAKARTA (1986)

HOFFMAN, STEPHEN L., FLANIGAN, TIMOTHY P., KLAUCKE, DOUGLAS, LEKSANA, BUDHI, ROCKHILL, ROBERT C., PUNJABI, NARAIN H., ...

The Widal slide agglutination test was evaluated as a rapid diagnostic test in typhoid fever patients at the infectious Diseases Hospital, Jakarta, Indonesia from 1980–1982. The results of the test...

Immunogenicity and in vitro protective efficacy of a recombinant multistage Plasmodium falciparum candidate vaccine

Shi, Ya Ping, Hasnain, Seyed E., Sacci, John B., Holloway, Brian P., Fujioka, Hisashi, Kumar, Nirbhay, ...

Compared with a single-stage antigen-based vaccine, a multistage and multivalent Plasmodium falciparum vaccine would be more efficacious by inducing “multiple layers” of immunity. We have...

Boosting with recombinant vaccinia increases immunogenicity and protective efficacy of malaria DNA vaccine

Sedegah, Martha, Jones, Trevor R., Kaur, Manjit, Hedstrom, Richard, Hobart, Peter, Tine, John A., ...

To enhance the efficacy of DNA malaria vaccines, we evaluated the effect on protection of immunizing with various combinations of DNA, recombinant vaccinia virus, and a synthetic peptide....

Exploring the transcriptome of the malaria sporozoite stage

Kappe, Stefan H. I., Gardner, Malcolm J., Brown, Stuart M., Ross, Jessica, Matuschewski, Kai, Ribeiro, Jose M., ...

Most studies of gene expression in Plasmodium have been concerned with asexual and/or sexual erythrocytic stages. Identification and cloning of genes expressed in the preerythrocytic stages lag far...

Induction of CD4+ T cell-dependent CD8+ type 1 responses in humans by a malaria DNA vaccine

Wang, Ruobing, Epstein, Judith, Baraceros, Fe Maria, Gorak, Edward J., Charoenvit, Yupin, Carucci, Daniel J., ...

We assessed immunogenicity of a malaria DNA vaccine administered by needle i.m. or needleless jet injection [i.m. or i.m./intradermally (i.d.)] in 14 volunteers. Antigen-specific IFN-γ responses...

Immune Response against the Exp-1 Protein of Plasmodium falciparum Results in Antibodies That Cross-React with Human T-Cell Lymphotropic Virus Type 1 Proteins

Porter, Kevin R., Aguiar, Joao, Richards, Allen, Sandjaya, B., Ignatias, H., Hadiputranto, H., ...

To examine the role of the Plasmodium falciparum Exp-1 blood-stage protein in producing antibodies that cross-react with human T-cell lymphotropic virus type I (HTLV-I) proteins, we studied sera from...

CD4+ T-Cell- and Gamma Interferon-Dependent Protection against Murine Malaria by Immunization with Linear Synthetic Peptides from a Plasmodium yoelii 17-Kilodalton Hepatocyte Erythrocyte Protein

Charoenvit, Yupin, Majam, Victoria Fallarme, Corradin, Giampietro, Sacci, John B., Wang, Ruobing, Doolan, Denise L., ...

Most work on protective immunity against the pre-erythrocytic stages of malaria has focused on induction of antibodies that prevent sporozoite invasion of hepatocytes, and CD8+ T-cell responses that...

Antibodies against the Plasmodium falciparum Receptor Binding Domain of EBA-175 Block Invasion Pathways That Do Not Involve Sialic Acids

Narum, David L., Haynes, J. David, Fuhrmann, Steven, Moch, Kathy, Liang, Hong, Hoffman, Stephen L., ...

The 175-kDa Plasmodium falciparum erythrocyte binding protein (EBA-175) binds to its receptor, sialic acids on glycophorin A. The binding region within EBA-175 is a cysteine-rich region identified as...

A Subdominant CD8+ Cytotoxic T Lymphocyte (CTL) Epitope from the Plasmodium yoelii Circumsporozoite Protein Induces CTLs That Eliminate Infected Hepatocytes from Culture

Franke, Eileen D., Sette, Alessandro, Sacci, John, Southwood, Scott, Corradin, Giampietro, Hoffman, Stephen L.

Previous studies indicated that the Plasmodium yoelii circumsporozoite protein (PyCSP) 57–70 region elicits T cells capable of eliminating infected hepatocytes in vitro. Herein, we report that the...

Expression, Extracellular Secretion, and Immunogenicity of the Plasmodium falciparum Sporozoite Surface Protein 2 in Salmonella Vaccine Strains

Gómez-Duarte, Oscar G., Pasetti, Marcela F., Santiago, Araceli, Sztein, Marcelo B., Hoffman, Stephen L., Levine, Myron M.

Deleting transmembrane α-helix motifs from Plasmodium falciparum sporozoite surface protein (SSP-2) allowed its secretion from Salmonella enterica serovar Typhimurium SL3261 and S. enterica serovar...

Interleukin-12- and Gamma Interferon-Dependent Protection against Malaria Conferred by CpG Oligodeoxynucleotide in Mice

Gramzinski, Robert A., Doolan, Denise L., Sedegah, Martha, Davis, Heather L., Krieg, Arthur M., Hoffman, Stephen L.

Unmethylated CpG dinucleotides in bacterial DNA or synthetic oligodeoxynucleotides (ODNs) cause B-cell proliferation and immunoglobulin secretion, monocyte cytokine secretion, and activation of...

HLA-A*01-Restricted Cytotoxic T-Lymphocyte Epitope from the Plasmodium falciparum Circumsporozoite Protein

Kumar, Anita, Kumar, Sanjai, Le, Thong P., Southwood, Scott, Sidney, John, Cohen, Joe, ...

Here, we report the identification of a novel CD8+ cytotoxic T-lymphocyte epitope on the Plasmodium falciparum circumsporozoite protein (3D7; amino acids 310 to 319 [EPSDKHIKEY]) that is restricted...

Immunogenicity and Protective Efficacy of a Plasmodium yoelii Hsp60 DNA Vaccine in BALB/c Mice

Sanchez, Gloria I., Sedegah, Martha, Rogers, William O., Jones, Trevor R., Sacci, John, Witney, Adam, ...

The gene encoding the 60-kDa heat shock protein of Plasmodium yoelii (PyHsp60) was cloned into the VR1012 and VR1020 mammalian expression vectors. Groups of 10 BALB/c mice were immunized...

Immunogenicity of Well-Characterized Synthetic Plasmodium falciparum Multiple Antigen Peptide Conjugates

Joshi, Manju B., Gam, Albert A., Boykins, Robert A., Kumar, Sanjai, Sacci, John, Hoffman, Stephen L., ...

Given the emerging difficulties with malaria drug resistance and vector control, as well as the persistent lack of an effective vaccine, new malaria vaccine development strategies are needed. We used...

Multistage Multiantigen Heterologous Prime Boost Vaccine for Plasmodium knowlesi Malaria Provides Partial Protection in Rhesus Macaques

Rogers, William O., Baird, J. Kevin, Kumar, Anita, Tine, John A., Weiss, Walter, Aguiar, João C., ...

A nonhuman primate model for malaria vaccine development allowing reliable, stringent sporozoite challenge and evaluation of both cellular and antibody responses is needed. We therefore constructed a...

Codon Optimization of Gene Fragments Encoding Plasmodium falciparum Merzoite Proteins Enhances DNA Vaccine Protein Expression and Immunogenicity in Mice

Narum, David L., Kumar, Sanjai, Rogers, William O., Fuhrmann, Steven R., Liang, Hong, Oakley, Miranda, ...

In contrast to conventional vaccines, DNA and other subunit vaccines exclusively utilize host cell molecules for transcription and translation of proteins. The adenine plus thymine content of...

Protection of Mice against Plasmodium yoelii Sporozoite Challenge with P. yoelii Merozoite Surface Protein 1 DNA Vaccines

Becker, Sylvia I., Wang, Ruobing, Hedstrom, Richard C., Aguiar, Joao C., Jones, Trevor R., Hoffman, Stephen L., ...

Immunization of mice with DNA vaccines encoding the full-length form and C and N termini of Plasmodium yoelii merozoite surface protein 1 provided partial protection against sporozoite challenge and...

Simultaneous Induction of Multiple Antigen-Specific Cytotoxic T Lymphocytes in Nonhuman Primates by Immunization with a Mixture of Four Plasmodium falciparum DNA Plasmids

Wang, Ruobing, Doolan, Denise L., Charoenvit, Yupin, Hedstrom, Richard C., Gardner, Malcolm J., Hobart, Peter, ...

CD8+ T cells have been implicated as critical effector cells in protective immunity against malaria parasites developing within hepatocytes. A vaccine that protects against malaria by inducing CD8+ T...

Persistence of Protective Immunity to Malaria Induced by DNA Priming and Poxvirus Boosting: Characterization of Effector and Memory CD8+-T-Cell Populations

Sedegah, Martha, Brice, Gary T., Rogers, William O., Doolan, Denise L., Charoenvit, Yupin, Jones, Trevor R., ...

The persistence of immunity to malaria induced in mice by a heterologous DNA priming and poxvirus boosting regimen was characterized. Mice were immunized by priming with DNA vaccine plasmids encoding...

Protection of Rhesus Macaques against Lethal Plasmodium knowlesi Malaria by a Heterologous DNA Priming and Poxvirus Boosting Immunization Regimen

Rogers, William O., Weiss, Walter R., Kumar, Anita, Aguiar, João C., Tine, John A., Gwadz, Robert, ...

We tested a cytokine-enhanced, multiantigen, DNA priming and poxvirus boosting vaccine regimen for prevention of malaria in the Plasmodium knowlesi-rhesus macaque model system. Animals were primed...

Identification of Plasmodium falciparum antigens by antigenic analysis of genomic and proteomic data

Doolan, Denise L., Southwood, Scott, Freilich, Daniel A., Sidney, John, Graber, Norma L., Shatney, Lori, ...

The recent explosion in genomic sequencing has made available a wealth of data that can now be analyzed to identify protein antigens, potential targets for vaccine development. Here we present, in...

Optical Mapping of Plasmodium falciparum Chromosome 2

Jing, Junping, Lai, Zhongwu, Aston, Christopher, Lin, Jieyi, Carucci, Daniel J., Gardner, Malcolm J., ...

Detailed restriction maps of microbial genomes are a valuable resource in genome sequencing studies but are toilsome to construct by contig construction of maps derived from cloned DNA. Analysis of...

CpG Oligodeoxynucleotide and Montanide ISA 51 Adjuvant Combination Enhanced the Protective Efficacy of a Subunit Malaria Vaccine

Kumar, Sanjai, Jones, Trevor R., Oakley, Miranda S., Zheng, Hong, Kuppusamy, Shanmuga P., Taye, Alem, ...

Unmethylated CpG dinucleotide motifs present in bacterial genomes or synthetic oligodeoxynucleotides (ODNs) serve as strong immunostimulatory agents in mice, monkeys and humans. We determined the...

Comparative Analysis of Apicomplexa and Genomic Diversity in Eukaryotes

Templeton, Thomas J., Iyer, Lakshminarayan M., Anantharaman, Vivek, Enomoto, Shinichiro, Abrahante, Juan E., Subramanian, G.M., ...

The apicomplexans Plasmodium and Cryptosporidium have developed distinctive adaptations via lineage-specific gene loss and gene innovation in the process of diverging from a common parasitic...

Comparative immunopeptidomics of humans and their pathogens

Istrail, Sorin, Florea, Liliana, Halldórsson, Bjarni V., Kohlbacher, Oliver, Schwartz, Russell S., Yap, Von Bing, ...

Major histocompatibility complex class I molecules present peptides of 8-10 residues to CD8+ T cells. We used 19 predicted proteomes to determine the influence of CD8+ T cell immune surveillance on...

High-Throughput Generation of P. falciparum Functional Molecules by Recombinational Cloning

Aguiar, João Carlos, LaBaer, Joshua, Blair, Peter L., Shamailova, Victoria Y., Koundinya, Malvika, Russell, Joshua A., ...

Large-scale functional genomics studies for malaria vaccine and drug development will depend on the generation of molecular tools to study protein expression. We examined the feasibility of a...

Boosting of DNA Vaccine-Elicited Gamma Interferon Responses in Humans by Exposure to Malaria Parasites

Wang, Ruobing, Richie, Thomas L., Baraceros, Maria Fe, Rahardjo, Nancy, Gay, Tanya, Banania, Jo-Glenna, ...

A mixture of DNA plasmids expressing five Plasmodium falciparum pre-erythrocyte-stage antigens was administered with or without a DNA plasmid encoding human granulocyte-macrophage colony-stimulating...

Immunogenicity and in vitro protective efficacy of a recombinant multistage Plasmodium falciparum candidate vaccine

Shi, Ya Ping, Hasnain, Seyed E., Sacci, John B., Holloway, Brian P., Fujioka, Hisashi, Kumar, Nirbhay, ...

Compared with a single-stage antigen-based vaccine, a multistage and multivalent Plasmodium falciparum vaccine would be more efficacious by inducing “multiple layers” of immunity. We have...

Boosting with recombinant vaccinia increases immunogenicity and protective efficacy of malaria DNA vaccine

Sedegah, Martha, Jones, Trevor R., Kaur, Manjit, Hedstrom, Richard, Hobart, Peter, Tine, John A., ...

To enhance the efficacy of DNA malaria vaccines, we evaluated the effect on protection of immunizing with various combinations of DNA, recombinant vaccinia virus, and a synthetic peptide....

Exploring the transcriptome of the malaria sporozoite stage

Kappe, Stefan H. I., Gardner, Malcolm J., Brown, Stuart M., Ross, Jessica, Matuschewski, Kai, Ribeiro, Jose M., ...

Most studies of gene expression in Plasmodium have been concerned with asexual and/or sexual erythrocytic stages. Identification and cloning of genes expressed in the preerythrocytic stages lag far...

Induction of CD4+ T cell-dependent CD8+ type 1 responses in humans by a malaria DNA vaccine

Wang, Ruobing, Epstein, Judith, Baraceros, Fe Maria, Gorak, Edward J., Charoenvit, Yupin, Carucci, Daniel J., ...

We assessed immunogenicity of a malaria DNA vaccine administered by needle i.m. or needleless jet injection [i.m. or i.m./intradermally (i.d.)] in 14 volunteers. Antigen-specific IFN-γ responses...

Immune Response against the Exp-1 Protein of Plasmodium falciparum Results in Antibodies That Cross-React with Human T-Cell Lymphotropic Virus Type 1 Proteins

Porter, Kevin R., Aguiar, Joao, Richards, Allen, Sandjaya, B., Ignatias, H., Hadiputranto, H., ...

To examine the role of the Plasmodium falciparum Exp-1 blood-stage protein in producing antibodies that cross-react with human T-cell lymphotropic virus type I (HTLV-I) proteins, we studied sera from...

CD4+ T-Cell- and Gamma Interferon-Dependent Protection against Murine Malaria by Immunization with Linear Synthetic Peptides from a Plasmodium yoelii 17-Kilodalton Hepatocyte Erythrocyte Protein

Charoenvit, Yupin, Majam, Victoria Fallarme, Corradin, Giampietro, Sacci, John B., Wang, Ruobing, Doolan, Denise L., ...

Most work on protective immunity against the pre-erythrocytic stages of malaria has focused on induction of antibodies that prevent sporozoite invasion of hepatocytes, and CD8+ T-cell responses that...

Antibodies against the Plasmodium falciparum Receptor Binding Domain of EBA-175 Block Invasion Pathways That Do Not Involve Sialic Acids

Narum, David L., Haynes, J. David, Fuhrmann, Steven, Moch, Kathy, Liang, Hong, Hoffman, Stephen L., ...

The 175-kDa Plasmodium falciparum erythrocyte binding protein (EBA-175) binds to its receptor, sialic acids on glycophorin A. The binding region within EBA-175 is a cysteine-rich region identified as...

A Subdominant CD8+ Cytotoxic T Lymphocyte (CTL) Epitope from the Plasmodium yoelii Circumsporozoite Protein Induces CTLs That Eliminate Infected Hepatocytes from Culture

Franke, Eileen D., Sette, Alessandro, Sacci, John, Southwood, Scott, Corradin, Giampietro, Hoffman, Stephen L.

Previous studies indicated that the Plasmodium yoelii circumsporozoite protein (PyCSP) 57–70 region elicits T cells capable of eliminating infected hepatocytes in vitro. Herein, we report that the...

Expression, Extracellular Secretion, and Immunogenicity of the Plasmodium falciparum Sporozoite Surface Protein 2 in Salmonella Vaccine Strains

Gómez-Duarte, Oscar G., Pasetti, Marcela F., Santiago, Araceli, Sztein, Marcelo B., Hoffman, Stephen L., Levine, Myron M.

Deleting transmembrane α-helix motifs from Plasmodium falciparum sporozoite surface protein (SSP-2) allowed its secretion from Salmonella enterica serovar Typhimurium SL3261 and S. enterica serovar...

Interleukin-12- and Gamma Interferon-Dependent Protection against Malaria Conferred by CpG Oligodeoxynucleotide in Mice

Gramzinski, Robert A., Doolan, Denise L., Sedegah, Martha, Davis, Heather L., Krieg, Arthur M., Hoffman, Stephen L.

Unmethylated CpG dinucleotides in bacterial DNA or synthetic oligodeoxynucleotides (ODNs) cause B-cell proliferation and immunoglobulin secretion, monocyte cytokine secretion, and activation of...

HLA-A*01-Restricted Cytotoxic T-Lymphocyte Epitope from the Plasmodium falciparum Circumsporozoite Protein

Kumar, Anita, Kumar, Sanjai, Le, Thong P., Southwood, Scott, Sidney, John, Cohen, Joe, ...

Here, we report the identification of a novel CD8+ cytotoxic T-lymphocyte epitope on the Plasmodium falciparum circumsporozoite protein (3D7; amino acids 310 to 319 [EPSDKHIKEY]) that is restricted...

Immunogenicity and Protective Efficacy of a Plasmodium yoelii Hsp60 DNA Vaccine in BALB/c Mice

Sanchez, Gloria I., Sedegah, Martha, Rogers, William O., Jones, Trevor R., Sacci, John, Witney, Adam, ...

The gene encoding the 60-kDa heat shock protein of Plasmodium yoelii (PyHsp60) was cloned into the VR1012 and VR1020 mammalian expression vectors. Groups of 10 BALB/c mice were immunized...

Immunogenicity of Well-Characterized Synthetic Plasmodium falciparum Multiple Antigen Peptide Conjugates

Joshi, Manju B., Gam, Albert A., Boykins, Robert A., Kumar, Sanjai, Sacci, John, Hoffman, Stephen L., ...

Given the emerging difficulties with malaria drug resistance and vector control, as well as the persistent lack of an effective vaccine, new malaria vaccine development strategies are needed. We used...

Multistage Multiantigen Heterologous Prime Boost Vaccine for Plasmodium knowlesi Malaria Provides Partial Protection in Rhesus Macaques

Rogers, William O., Baird, J. Kevin, Kumar, Anita, Tine, John A., Weiss, Walter, Aguiar, João C., ...

A nonhuman primate model for malaria vaccine development allowing reliable, stringent sporozoite challenge and evaluation of both cellular and antibody responses is needed. We therefore constructed a...

Codon Optimization of Gene Fragments Encoding Plasmodium falciparum Merzoite Proteins Enhances DNA Vaccine Protein Expression and Immunogenicity in Mice

Narum, David L., Kumar, Sanjai, Rogers, William O., Fuhrmann, Steven R., Liang, Hong, Oakley, Miranda, ...

In contrast to conventional vaccines, DNA and other subunit vaccines exclusively utilize host cell molecules for transcription and translation of proteins. The adenine plus thymine content of...

Protection of Mice against Plasmodium yoelii Sporozoite Challenge with P. yoelii Merozoite Surface Protein 1 DNA Vaccines

Becker, Sylvia I., Wang, Ruobing, Hedstrom, Richard C., Aguiar, Joao C., Jones, Trevor R., Hoffman, Stephen L., ...

Immunization of mice with DNA vaccines encoding the full-length form and C and N termini of Plasmodium yoelii merozoite surface protein 1 provided partial protection against sporozoite challenge and...

Simultaneous Induction of Multiple Antigen-Specific Cytotoxic T Lymphocytes in Nonhuman Primates by Immunization with a Mixture of Four Plasmodium falciparum DNA Plasmids

Wang, Ruobing, Doolan, Denise L., Charoenvit, Yupin, Hedstrom, Richard C., Gardner, Malcolm J., Hobart, Peter, ...

CD8+ T cells have been implicated as critical effector cells in protective immunity against malaria parasites developing within hepatocytes. A vaccine that protects against malaria by inducing CD8+ T...

Persistence of Protective Immunity to Malaria Induced by DNA Priming and Poxvirus Boosting: Characterization of Effector and Memory CD8+-T-Cell Populations

Sedegah, Martha, Brice, Gary T., Rogers, William O., Doolan, Denise L., Charoenvit, Yupin, Jones, Trevor R., ...

The persistence of immunity to malaria induced in mice by a heterologous DNA priming and poxvirus boosting regimen was characterized. Mice were immunized by priming with DNA vaccine plasmids encoding...

Protection of Rhesus Macaques against Lethal Plasmodium knowlesi Malaria by a Heterologous DNA Priming and Poxvirus Boosting Immunization Regimen

Rogers, William O., Weiss, Walter R., Kumar, Anita, Aguiar, João C., Tine, John A., Gwadz, Robert, ...

We tested a cytokine-enhanced, multiantigen, DNA priming and poxvirus boosting vaccine regimen for prevention of malaria in the Plasmodium knowlesi-rhesus macaque model system. Animals were primed...

Identification of Plasmodium falciparum antigens by antigenic analysis of genomic and proteomic data

Doolan, Denise L., Southwood, Scott, Freilich, Daniel A., Sidney, John, Graber, Norma L., Shatney, Lori, ...

The recent explosion in genomic sequencing has made available a wealth of data that can now be analyzed to identify protein antigens, potential targets for vaccine development. Here we present, in...

Optical Mapping of Plasmodium falciparum Chromosome 2

Jing, Junping, Lai, Zhongwu, Aston, Christopher, Lin, Jieyi, Carucci, Daniel J., Gardner, Malcolm J., ...

Detailed restriction maps of microbial genomes are a valuable resource in genome sequencing studies but are toilsome to construct by contig construction of maps derived from cloned DNA. Analysis of...

CpG Oligodeoxynucleotide and Montanide ISA 51 Adjuvant Combination Enhanced the Protective Efficacy of a Subunit Malaria Vaccine

Kumar, Sanjai, Jones, Trevor R., Oakley, Miranda S., Zheng, Hong, Kuppusamy, Shanmuga P., Taye, Alem, ...

Unmethylated CpG dinucleotide motifs present in bacterial genomes or synthetic oligodeoxynucleotides (ODNs) serve as strong immunostimulatory agents in mice, monkeys and humans. We determined the...

Comparative Analysis of Apicomplexa and Genomic Diversity in Eukaryotes

Templeton, Thomas J., Iyer, Lakshminarayan M., Anantharaman, Vivek, Enomoto, Shinichiro, Abrahante, Juan E., Subramanian, G.M., ...

The apicomplexans Plasmodium and Cryptosporidium have developed distinctive adaptations via lineage-specific gene loss and gene innovation in the process of diverging from a common parasitic...

Comparative immunopeptidomics of humans and their pathogens

Istrail, Sorin, Florea, Liliana, Halldórsson, Bjarni V., Kohlbacher, Oliver, Schwartz, Russell S., Yap, Von Bing, ...

Major histocompatibility complex class I molecules present peptides of 8-10 residues to CD8+ T cells. We used 19 predicted proteomes to determine the influence of CD8+ T cell immune surveillance on...

High-Throughput Generation of P. falciparum Functional Molecules by Recombinational Cloning

Aguiar, João Carlos, LaBaer, Joshua, Blair, Peter L., Shamailova, Victoria Y., Koundinya, Malvika, Russell, Joshua A., ...

Large-scale functional genomics studies for malaria vaccine and drug development will depend on the generation of molecular tools to study protein expression. We examined the feasibility of a...

Boosting of DNA Vaccine-Elicited Gamma Interferon Responses in Humans by Exposure to Malaria Parasites

Wang, Ruobing, Richie, Thomas L., Baraceros, Maria Fe, Rahardjo, Nancy, Gay, Tanya, Banania, Jo-Glenna, ...

A mixture of DNA plasmids expressing five Plasmodium falciparum pre-erythrocyte-stage antigens was administered with or without a DNA plasmid encoding human granulocyte-macrophage colony-stimulating...

Gene Disruption of Plasmodium falciparum p52 Results in Attenuation of Malaria Liver Stage Development in Cultured Primary Human Hepatocytes

Janse, Chris J., Van Gemert, Geert-Jan, Van Dijk, Melissa R., Gego, Audrey, Franetich, Jean-Francois, ...

Difficulties with inducing sterile and long lasting protective immunity against malaria with subunit vaccines has renewed interest in vaccinations with attenuated Plasmodium parasites. Immunizations...