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Article ; Online: Majority of human circulating IgG plasmablasts stop blasting in a cell-free pro-survival culture.

Nguyen, Doan C / Saney, Celia / Hentenaar, Ian T / Cabrera-Mora, Monica / Capric, Violeta / Woodruff, Matthew C / Andrews, Joel / Lonial, Sagar / Sanz, Ignacio / Lee, F Eun-Hyung

Scientific reports

2024 Volume 14, Issue 1, Page(s) 3616

Abstract: Following infection or vaccination, early-minted antibody secreting cells (ASC) or plasmablasts appear in circulation transiently, and a small fraction migrates to the spleen or bone marrow (BM) to mature into long-lived plasma cells (LLPC). While LLPC, ... ...

Abstract	Following infection or vaccination, early-minted antibody secreting cells (ASC) or plasmablasts appear in circulation transiently, and a small fraction migrates to the spleen or bone marrow (BM) to mature into long-lived plasma cells (LLPC). While LLPC, by definition, are quiescent or non-dividing, the majority of blood ASC are thought to be "blasting" or proliferative. In this study, we find > 95% nascent blood ASC in culture express Ki-67 but only 6-12% incorporate BrdU after 4 h or 24 h labeling. In contrast, < 5% BM LLPC in culture are Ki-67
MeSH term(s)	Humans ; Plasma Cells/metabolism ; Ki-67 Antigen ; Bone Marrow/metabolism ; Immunoglobulin G ; Antigens, CD19/metabolism
Chemical Substances	Ki-67 Antigen ; Immunoglobulin G ; Antigens, CD19
Language	English
Publishing date	2024-02-13
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-53977-2
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Majority of human circulating plasmablasts stop blasting: A probable misnomer.

Nguyen, Doan C / Saney, Celia / Hentenaar, Ian T / Cabrera-Mora, Monica / Woodruff, Matthew C / Andrews, Joel / Lonial, Sagar / Sanz, Ignacio / Lee, F Eun-Hyung

bioRxiv : the preprint server for biology

2023

Abstract	Following infection or vaccination, early-minted antibody secreting cells (ASC) or plasmablasts appear in circulation transiently, and a small fraction migrates to the spleen or bone marrow (BM) to mature into long-lived plasma cells (LLPC). While LLPC, by definition, are quiescent or non-dividing, the majority of blood ASC are thought to be "blasting" or proliferative. In this study, we find >95% nascent blood ASC in culture express Ki-67 but only 6-12% incorporate BrdU after 4h or 24h labeling. In contrast, <5% BM LLPC in culture are Ki-67
Language	English
Publishing date	2023-09-13
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.09.10.557057
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Article ; Online: Malaria disrupts the rhesus macaque gut microbiome.

Farinella, Danielle N / Kaur, Sukhpreet / Tran, ViLinh / Cabrera-Mora, Monica / Joyner, Chester J / Lapp, Stacey A / Pakala, Suman B / Nural, Mustafa V / DeBarry, Jeremy D / Kissinger, Jessica C / Jones, Dean P / Moreno, Alberto / Galinski, Mary R / Cordy, Regina Joice

Frontiers in cellular and infection microbiology

2023 Volume 12, Page(s) 1058926

Abstract: Previous studies have suggested that a relationship exists between severity and transmissibility of malaria and variations in the gut microbiome, yet only limited information exists on the temporal dynamics of the gut microbial community during a ... ...

Abstract	Previous studies have suggested that a relationship exists between severity and transmissibility of malaria and variations in the gut microbiome, yet only limited information exists on the temporal dynamics of the gut microbial community during a malarial infection. Here, using a rhesus macaque model of relapsing malaria, we investigate how malaria affects the gut microbiome. In this study, we performed 16S sequencing on DNA isolated from rectal swabs of rhesus macaques over the course of an experimental malarial infection with
MeSH term(s)	Animals ; Humans ; Macaca mulatta/genetics ; Macaca mulatta/metabolism ; Gastrointestinal Microbiome ; Malaria/parasitology ; Malaria, Vivax/parasitology ; Plasmodium cynomolgi/genetics ; Plasmodium cynomolgi/metabolism ; Bacteria/genetics ; RNA, Ribosomal, 16S/genetics
Chemical Substances	RNA, Ribosomal, 16S
Language	English
Publishing date	2023-01-13
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2022.1058926
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Article ; Online: A Multi-Stage

McCaffery, Jessica N / Fonseca, Jairo A / Singh, Balwan / Cabrera-Mora, Monica / Bohannon, Caitlin / Jacob, Joshy / Arévalo-Herrera, Myriam / Moreno, Alberto

Frontiers in cellular and infection microbiology

2019 Volume 9, Page(s) 135

Abstract: Malaria control and interventions including long-lasting insecticide-treated nets, indoor residual spraying, and intermittent preventative treatment in pregnancy have resulted in a significant reduction in the number ... ...

Abstract	Malaria control and interventions including long-lasting insecticide-treated nets, indoor residual spraying, and intermittent preventative treatment in pregnancy have resulted in a significant reduction in the number of
MeSH term(s)	Animals ; Antibodies, Protozoan/blood ; Antibody Formation ; Antigens, Protozoan/immunology ; Antigens, Surface/immunology ; Chromobox Protein Homolog 5 ; Disease Transmission, Infectious/prevention & control ; Malaria Vaccines/administration & dosage ; Malaria Vaccines/immunology ; Malaria, Vivax/prevention & control ; Malaria, Vivax/transmission ; Merozoite Surface Protein 1/immunology ; Mice ; Plasmodium vivax/immunology ; Recombinant Fusion Proteins/immunology ; Time Factors ; Vaccines, Synthetic/administration & dosage ; Vaccines, Synthetic/immunology
Chemical Substances	Antibodies, Protozoan ; Antigens, Protozoan ; Antigens, Surface ; CBX5 protein, human ; Malaria Vaccines ; Merozoite Surface Protein 1 ; Pvs25 protein, P vivax ; Recombinant Fusion Proteins ; Vaccines, Synthetic ; Chromobox Protein Homolog 5 (107283-02-3)
Language	English
Publishing date	2019-05-01
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2019.00135
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Article ; Online: A hybrid multistage protein vaccine induces protective immunity against murine malaria.

Singh, Balwan / Cabrera-Mora, Monica / Jiang, Jianlin / Moreno, Alberto

Infection and immunity

2012 Volume 80, Issue 4, Page(s) 1491–1501

Abstract: We have previously reported the design and expression of chimeric recombinant proteins as an effective platform to deliver malaria vaccines. The erythrocytic and exoerythrocytic protein chimeras described included autologous T helper epitopes genetically ...

Abstract	We have previously reported the design and expression of chimeric recombinant proteins as an effective platform to deliver malaria vaccines. The erythrocytic and exoerythrocytic protein chimeras described included autologous T helper epitopes genetically linked to defined B cell epitopes. Proof-of-principle studies using vaccine constructs based on the Plasmodium yoelii circumsporozoite protein (CSP) and P. yoelii merozoite surface protein-1 (MSP-1) showed encouraging results when tested individually in this mouse malaria model. To evaluate the potential synergistic or additive effect of combining these chimeric antigens, we constructed a synthetic gene encoding a hybrid protein that combined both polypeptides in a single immunogen. The multistage vaccine was expressed in soluble form in Escherichia coli at high yield. Here we report that the multistage protein induced robust immune responses to individual components, with no evidence of vaccine interference. Passive immunization using purified IgG from rabbits immunized with the hybrid protein conferred more robust protection against the experimental challenge with P. yoelii sporozoites than passive immunization with purified IgG from rabbits immunized with the individual proteins. High antibody titers and high frequencies of CD4(+)- and CD8(+)-specific cytokine-secreting T cells were elicited by vaccination. T cells were multifunctional and able to simultaneously produce interleukin-2 (IL-2), gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α). The mechanism of vaccine-induced protection involved neutralizing antibodies and effector CD4(+) T cells and resulted in the control of hyperparasitemia and protection against malarial anemia. These data support our strategy of using an array of autologous T helper epitopes to maximize the response to multistage malaria vaccines.
MeSH term(s)	Animals ; Antibodies, Neutralizing/biosynthesis ; Antibodies, Neutralizing/immunology ; Antibodies, Protozoan/biosynthesis ; Antibodies, Protozoan/immunology ; Antigens, Protozoan/immunology ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; Female ; Immunization, Passive ; Interferon-gamma/biosynthesis ; Interleukin-2/biosynthesis ; Malaria/immunology ; Malaria/prevention & control ; Malaria Vaccines/immunology ; Merozoite Surface Protein 1/genetics ; Merozoite Surface Protein 1/immunology ; Mice ; Plasmodium yoelii/immunology ; Plasmodium yoelii/pathogenicity ; Protozoan Proteins/genetics ; Protozoan Proteins/immunology ; Rabbits ; Recombinant Fusion Proteins/immunology ; Tumor Necrosis Factor-alpha/biosynthesis
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Protozoan ; Antigens, Protozoan ; Interleukin-2 ; Malaria Vaccines ; Merozoite Surface Protein 1 ; Protozoan Proteins ; Recombinant Fusion Proteins ; Tumor Necrosis Factor-alpha ; circumsporozoite protein, Protozoan ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2012-01-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	218698-6
ISSN	1098-5522 ; 0019-9567
ISSN (online)	1098-5522
ISSN	0019-9567
DOI	10.1128/IAI.05980-11
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Article ; Online: A Recombinant Chimeric Ad5/3 Vector Expressing a Multistage Plasmodium Antigen Induces Protective Immunity in Mice Using Heterologous Prime-Boost Immunization Regimens.

Cabrera-Mora, Monica / Fonseca, Jairo Andres / Singh, Balwan / Zhao, Chunxia / Makarova, Natalia / Dmitriev, Igor / Curiel, David T / Blackwell, Jerry / Moreno, Alberto

Journal of immunology (Baltimore, Md. : 1950)

2016 Volume 197, Issue 7, Page(s) 2748–2761

Abstract: An ideal malaria vaccine should target several stages of the parasite life cycle and induce antiparasite and antidisease immunity. We have reported a Plasmodium yoelii chimeric multistage recombinant protein (P. yoelii linear peptide chimera/recombinant ... ...

Abstract	An ideal malaria vaccine should target several stages of the parasite life cycle and induce antiparasite and antidisease immunity. We have reported a Plasmodium yoelii chimeric multistage recombinant protein (P. yoelii linear peptide chimera/recombinant modular chimera), engineered to express several autologous T cell epitopes and sequences derived from the circumsporozoite protein and the merozoite surface protein 1. This chimeric protein elicits protective immunity, mediated by CD4(+) T cells and neutralizing Abs. However, experimental evidence, from pre-erythrocytic vaccine candidates and irradiated sporozoites, has shown that CD8(+) T cells play a significant role in protection. Recombinant viral vectors have been used as a vaccine platform to elicit effective CD8(+) T cell responses. The human adenovirus (Ad) serotype 5 has been tested in malaria vaccine clinical trials with excellent safety profile. Nevertheless, a major concern for the use of Ad5 is the high prevalence of anti-vector neutralizing Abs in humans, hampering its immunogenicity. To minimize the impact of anti-vector pre-existing immunity, we developed a chimeric Ad5/3 vector in which the knob region of Ad5 was replaced with that of Ad3, conferring partial resistance to anti-Ad5 neutralizing Abs. Furthermore, we implemented heterologous Ad/protein immunization regimens that include a single immunization with recombinant Ad vectors. Our data show that immunization with the recombinant Ad5/3 vector induces protective efficacy indistinguishable from that elicited by Ad5. Our study also demonstrates that the dose of the Ad vectors has an impact on the memory profile and protective efficacy. The results support further studies with Ad5/3 for malaria vaccine development.
MeSH term(s)	Adenoviruses, Human/genetics ; Animals ; Antigens, Protozoan/genetics ; Antigens, Protozoan/immunology ; CD8-Positive T-Lymphocytes/immunology ; Female ; Genetic Vectors/genetics ; HEK293 Cells ; Humans ; Immunity, Cellular/immunology ; Malaria Vaccines/genetics ; Malaria Vaccines/immunology ; Mice ; Mice, Transgenic ; Plasmodium yoelii/immunology ; Recombinant Proteins/genetics ; Recombinant Proteins/immunology
Chemical Substances	Antigens, Protozoan ; Malaria Vaccines ; Recombinant Proteins
Language	English
Publishing date	2016-08-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.1501926
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Article ; Online: Plasmodium cynomolgi infections in rhesus macaques display clinical and parasitological features pertinent to modelling vivax malaria pathology and relapse infections.

Joyner, Chester / Moreno, Alberto / Meyer, Esmeralda V S / Cabrera-Mora, Monica / Kissinger, Jessica C / Barnwell, John W / Galinski, Mary R

Malaria journal

2016 Volume 15, Issue 1, Page(s) 451

Abstract: Background: Plasmodium vivax infections in humans or in new world monkeys pose research challenges that necessitate the use of alternative model systems. Plasmodium cynomolgi is a closely related species that shares genetic and biological ... ...

Abstract	Background: Plasmodium vivax infections in humans or in new world monkeys pose research challenges that necessitate the use of alternative model systems. Plasmodium cynomolgi is a closely related species that shares genetic and biological characteristics with P. vivax, including relapses. Here, the haematological dynamics and clinical presentation of sporozoite-initiated P. cynomolgi infections in Macaca mulatta (rhesus macaques) are evaluated over a 100-day period. Methods: Five M. mulatta were inoculated with 2000 P. cynomolgi B strain sporozoites. Parasitological and haematological data were collected daily to study the clinical presentations of primary infections and relapses. Peripheral blood and bone marrow aspirates were collected at specific time points during infection for future and retrospective systems biology analyses. Results: Patent infections were observed between days 10 and 12, and the acute, primary infection consisted of parasitaemias ranging from 269,962 to 1,214,842 parasites/µl (4.42-19.5 % parasitaemia). All animals presented with anaemia, ranging from moderate (7-10 g/dl) to severe (<7 g/dl), based on peripheral haemoglobin concentrations. Minimum haemoglobin levels coincided with the clearance of parasites and peripheral reticulocytosis was evident at this time. Mild thrombocytopaenia (<150,000 platelets/µl) was observed in all animals, but unlike haemoglobin, platelets were lowest whenever peripheral parasitaemia peaked. The animals' conditions were classified as non-severe, severe or lethal (in one case) based upon their clinical presentation. The lethal phenotype presented uniquely with an exceptionally high parasitaemia (19.5 %) and lack of a modest reticulocyte release, which was observed in the other animals prior to acute manifestations. One or two relapses were observed in the four surviving animals, and these were characterized by significantly lower parasitaemias and minimal changes in clinical parameters compared to pre-infection values. Conclusions: Rhesus macaque infections initiated by P. cynomolgi B strain sporozoites recapitulated pathology of human malaria, including anaemia and thrombocytopaenia, with inter-individual differences in disease severity. Importantly, this study provides an in-depth assessment of clinical and parasitological data, and shows that unlike the primary infections, the relapses did not cause clinical malaria. Notably, this body of research has provided experimental plans, large accessible datasets, and blood and bone marrow samples pertinent for ongoing and iterative systems biology investigations.
MeSH term(s)	Anemia/etiology ; Anemia/pathology ; Animals ; Female ; Macaca mulatta ; Malaria/complications ; Malaria/parasitology ; Malaria/pathology ; Malaria/veterinary ; Male ; Plasmodium cynomolgi/isolation & purification ; Recurrence ; Thrombocytopenia/etiology ; Thrombocytopenia/pathology
Language	English
Publishing date	2016-09-02
Publishing country	England
Document type	Journal Article
ISSN	1475-2875
ISSN (online)	1475-2875
DOI	10.1186/s12936-016-1480-6
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Article ; Online: Plasmodium knowlesi

Peterson, Mariko S / Joyner, Chester J / Lapp, Stacey A / Brady, Jessica A / Wood, Jennifer S / Cabrera-Mora, Monica / Saney, Celia L / Fonseca, Luis L / Cheng, Wayne T / Jiang, Jianlin / Soderberg, Stephanie R / Nural, Mustafa V / Hankus, Allison / Machiah, Deepa / Karpuzoglu, Ebru / DeBarry, Jeremy D / Tirouvanziam, Rabindra / Kissinger, Jessica C / Moreno, Alberto /

Gumber, Sanjeev / Voit, Eberhard O / Gutierrez, Juan B / Cordy, Regina Joice / Galinski, Mary R

Frontiers in cellular and infection microbiology

2022 Volume 12, Page(s) 888496

Abstract: Plasmodium ... ...

Abstract	Plasmodium knowlesi
MeSH term(s)	Agglutination ; Animals ; Antigens ; Erythrocyte Membrane ; Erythrocytes/parasitology ; Macaca mulatta ; Malaria/parasitology ; Plasmodium ; Plasmodium knowlesi/genetics ; Schizonts
Chemical Substances	Antigens
Language	English
Publishing date	2022-06-23
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2022.888496
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Article ; Online: Dysregulated naive B cells and de novo autoreactivity in severe COVID-19.

Woodruff, Matthew C / Ramonell, Richard P / Haddad, Natalie S / Anam, Fabliha A / Rudolph, Mark E / Walker, Tiffany A / Truong, Alexander D / Dixit, Adviteeya N / Han, Jenny E / Cabrera-Mora, Monica / Runnstrom, Martin C / Bugrovsky, Regina / Hom, Jennifer / Connolly, Erin C / Albizua, Igor / Javia, Vidhi / Cashman, Kevin S / Nguyen, Doan C / Kyu, Shuya /

Singh Saini, Ankur / Piazza, Michael / Tipton, Christopher M / Khosroshahi, Arezou / Gibson, Greg / Martin, Greg S / Maier, Cheryl L / Esper, Annette / Jenks, Scott A / Lee, F Eun-Hyung / Sanz, Ignacio

Nature

2022 Volume 611, Issue 7934, Page(s) 139–147

Abstract: Severe SARS-CoV-2 ... ...

Abstract	Severe SARS-CoV-2 infection
MeSH term(s)	Humans ; Autoantibodies/immunology ; B-Lymphocytes/immunology ; B-Lymphocytes/pathology ; COVID-19/immunology ; COVID-19/pathology ; COVID-19/physiopathology ; SARS-CoV-2/immunology ; SARS-CoV-2/pathogenicity ; Immunoglobulin G/immunology ; Single-Cell Analysis ; Autoantigens/immunology ; Basement Membrane/immunology
Chemical Substances	Autoantibodies ; Immunoglobulin G ; Autoantigens
Language	English
Publishing date	2022-08-31
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/s41586-022-05273-0
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Zs.A 26: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Genetic linkage of autologous T cell epitopes in a chimeric recombinant construct improves anti-parasite and anti-disease protective effect of a malaria vaccine candidate.

Singh, Balwan / Cabrera-Mora, Monica / Jiang, Jianlin / Galinski, Mary / Moreno, Alberto

Vaccine

2010 Volume 28, Issue 14, Page(s) 2580–2592

Abstract: We have reported the design of polyvalent synthetic and recombinant chimeras that include promiscuous T cell epitopes as a viable delivery system for pre-erythrocytic subunit malaria vaccines. To further assess the ability of several Plasmodium T cell ... ...

Abstract	We have reported the design of polyvalent synthetic and recombinant chimeras that include promiscuous T cell epitopes as a viable delivery system for pre-erythrocytic subunit malaria vaccines. To further assess the ability of several Plasmodium T cell epitopes to enhance vaccine potency, we designed a synthetic gene encoding four Plasmodium yoelii merozoite surface protein 1 (PyMSP1) CD4(+) promiscuous T cell epitopes fused in tandem to the homologous carboxyl terminal PyMSP1(19) fragment. This Recombinant Modular Chimera (PyRMC-MSP1(19)) was tested for immunogenicity and protective efficacy in comparative experiments with a recombinant protein expressing only the PyMSP1(19) fragment. Both proteins induced comparable antibody responses. However PyRMC-MSP1(19) elicited higher anti-parasite antibody titers and more robust protection against both hyper-parasitemia and malarial anemia. Most importantly, passive transfer of anti-PyRMC-MSP1(19), but not anti-PyMSP1(19) antibodies protected against heterologous challenge. These studies show that protective efficacy can be significantly improved by inclusion of an array of autologous promiscuous T cell epitopes in vaccine constructs.
MeSH term(s)	Amino Acid Sequence ; Anemia/prevention & control ; Animals ; Antibodies, Protozoan/blood ; Base Sequence ; Epitopes, T-Lymphocyte/genetics ; Epitopes, T-Lymphocyte/immunology ; Female ; Humans ; Immunization, Passive ; Malaria/prevention & control ; Malaria Vaccines/genetics ; Malaria Vaccines/immunology ; Male ; Merozoite Surface Protein 1/genetics ; Merozoite Surface Protein 1/immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Molecular Sequence Data ; Parasitemia/prevention & control ; Plasmodium yoelii/genetics ; Plasmodium yoelii/immunology ; Vaccines, Subunit/genetics ; Vaccines, Subunit/immunology ; Vaccines, Synthetic/genetics ; Vaccines, Synthetic/immunology
Chemical Substances	Antibodies, Protozoan ; Epitopes, T-Lymphocyte ; Malaria Vaccines ; Merozoite Surface Protein 1 ; Vaccines, Subunit ; Vaccines, Synthetic
Language	English
Publishing date	2010-01-22
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2010.01.019
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