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Antibodies elicited by Plasmodium falciparum circumsporozoite proteins lacking sequentially deleted C-terminal amino acids reveal mouse strain and epitopes specific differences
by
Zavala, Fidel
, Simonyan, Hayk
, Young, Colin N.
, Hayashi, Clifford T.H.
, Cao, Yi
, Kumar, Nirbhay
in
Allergy and Immunology
/ amino acid sequences
/ Amino acids
/ Animals
/ Antibodies
/ Antibodies, Protozoan - immunology
/ Antigens
/ B-lymphocytes
/ CD4 antigen
/ CD8 antigen
/ Circumsporozoite protein
/ Deoxyribonucleic acid
/ DNA
/ DNA vaccines
/ domain
/ Effectiveness
/ Electroporation
/ Enzymes
/ Epitopes
/ Epitopes - genetics
/ Epitopes - immunology
/ Epitopes, B-Lymphocyte - genetics
/ Epitopes, B-Lymphocyte - immunology
/ Epitopes, T-Lymphocyte - genetics
/ Epitopes, T-Lymphocyte - immunology
/ falciparum malaria
/ Female
/ genetically modified organisms
/ Immunization
/ Immunogenicity
/ Immunomodulation
/ Infections
/ Laboratory animals
/ Lymphocytes
/ Lymphocytes T
/ Malaria
/ Malaria Vaccines - administration & dosage
/ Malaria Vaccines - genetics
/ Malaria Vaccines - immunology
/ Malaria, Falciparum - immunology
/ Malaria, Falciparum - prevention & control
/ Mice
/ Mice, Inbred BALB C
/ Parasitic diseases
/ Plasmids
/ Plasmodium falciparum
/ Plasmodium falciparum - genetics
/ Plasmodium falciparum - immunology
/ Protein expression
/ Proteins
/ Protozoan Proteins - genetics
/ Protozoan Proteins - immunology
/ sporozoites
/ Sporozoites - immunology
/ T-lymphocytes
/ Vaccine
/ Vaccines
/ Vaccines, DNA - administration & dosage
/ Vaccines, DNA - genetics
/ Vaccines, DNA - immunology
/ Vector-borne diseases
2023
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Antibodies elicited by Plasmodium falciparum circumsporozoite proteins lacking sequentially deleted C-terminal amino acids reveal mouse strain and epitopes specific differences
by
Zavala, Fidel
, Simonyan, Hayk
, Young, Colin N.
, Hayashi, Clifford T.H.
, Cao, Yi
, Kumar, Nirbhay
in
Allergy and Immunology
/ amino acid sequences
/ Amino acids
/ Animals
/ Antibodies
/ Antibodies, Protozoan - immunology
/ Antigens
/ B-lymphocytes
/ CD4 antigen
/ CD8 antigen
/ Circumsporozoite protein
/ Deoxyribonucleic acid
/ DNA
/ DNA vaccines
/ domain
/ Effectiveness
/ Electroporation
/ Enzymes
/ Epitopes
/ Epitopes - genetics
/ Epitopes - immunology
/ Epitopes, B-Lymphocyte - genetics
/ Epitopes, B-Lymphocyte - immunology
/ Epitopes, T-Lymphocyte - genetics
/ Epitopes, T-Lymphocyte - immunology
/ falciparum malaria
/ Female
/ genetically modified organisms
/ Immunization
/ Immunogenicity
/ Immunomodulation
/ Infections
/ Laboratory animals
/ Lymphocytes
/ Lymphocytes T
/ Malaria
/ Malaria Vaccines - administration & dosage
/ Malaria Vaccines - genetics
/ Malaria Vaccines - immunology
/ Malaria, Falciparum - immunology
/ Malaria, Falciparum - prevention & control
/ Mice
/ Mice, Inbred BALB C
/ Parasitic diseases
/ Plasmids
/ Plasmodium falciparum
/ Plasmodium falciparum - genetics
/ Plasmodium falciparum - immunology
/ Protein expression
/ Proteins
/ Protozoan Proteins - genetics
/ Protozoan Proteins - immunology
/ sporozoites
/ Sporozoites - immunology
/ T-lymphocytes
/ Vaccine
/ Vaccines
/ Vaccines, DNA - administration & dosage
/ Vaccines, DNA - genetics
/ Vaccines, DNA - immunology
/ Vector-borne diseases
2023
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Antibodies elicited by Plasmodium falciparum circumsporozoite proteins lacking sequentially deleted C-terminal amino acids reveal mouse strain and epitopes specific differences
by
Zavala, Fidel
, Simonyan, Hayk
, Young, Colin N.
, Hayashi, Clifford T.H.
, Cao, Yi
, Kumar, Nirbhay
in
Allergy and Immunology
/ amino acid sequences
/ Amino acids
/ Animals
/ Antibodies
/ Antibodies, Protozoan - immunology
/ Antigens
/ B-lymphocytes
/ CD4 antigen
/ CD8 antigen
/ Circumsporozoite protein
/ Deoxyribonucleic acid
/ DNA
/ DNA vaccines
/ domain
/ Effectiveness
/ Electroporation
/ Enzymes
/ Epitopes
/ Epitopes - genetics
/ Epitopes - immunology
/ Epitopes, B-Lymphocyte - genetics
/ Epitopes, B-Lymphocyte - immunology
/ Epitopes, T-Lymphocyte - genetics
/ Epitopes, T-Lymphocyte - immunology
/ falciparum malaria
/ Female
/ genetically modified organisms
/ Immunization
/ Immunogenicity
/ Immunomodulation
/ Infections
/ Laboratory animals
/ Lymphocytes
/ Lymphocytes T
/ Malaria
/ Malaria Vaccines - administration & dosage
/ Malaria Vaccines - genetics
/ Malaria Vaccines - immunology
/ Malaria, Falciparum - immunology
/ Malaria, Falciparum - prevention & control
/ Mice
/ Mice, Inbred BALB C
/ Parasitic diseases
/ Plasmids
/ Plasmodium falciparum
/ Plasmodium falciparum - genetics
/ Plasmodium falciparum - immunology
/ Protein expression
/ Proteins
/ Protozoan Proteins - genetics
/ Protozoan Proteins - immunology
/ sporozoites
/ Sporozoites - immunology
/ T-lymphocytes
/ Vaccine
/ Vaccines
/ Vaccines, DNA - administration & dosage
/ Vaccines, DNA - genetics
/ Vaccines, DNA - immunology
/ Vector-borne diseases
2023
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Antibodies elicited by Plasmodium falciparum circumsporozoite proteins lacking sequentially deleted C-terminal amino acids reveal mouse strain and epitopes specific differences
Journal Article
Antibodies elicited by Plasmodium falciparum circumsporozoite proteins lacking sequentially deleted C-terminal amino acids reveal mouse strain and epitopes specific differences
2023
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Overview
Malaria affects ∼ ¼ billion people globally and requires the development of additional tools to aid in elimination efforts. The recently approved RTS,S/AS01 vaccine represents a positive step, however, the moderate efficacy necessitates the development of more efficacious vaccines. PfCSP is a key target antigen for pre-erythrocytic vaccines aimed at preventing Plasmodium falciparum malaria infections. Epitopes within the central repeat region and at the junction of the repeat and N-terminal domain are well documented as major protective B cell epitopes. On the other hand, a majority of antibodies against the epitopes in the C-terminal domain, have been shown to be non-protective against sporozoite challenge. The C-terminal domain, however, contains CD4+ and CD8+ T cell epitopes previously shown to be important for regulating immune responses. The present study was designed to further explore the immunomodulatory potential of the C-terminal domain using DNA vaccines encoding PfCSP with sequential C-terminal truncations following known T cell epitopes. Five DNA vaccines encoding different truncations of PfCSP within the C-terminal domain were administered via intramuscular route and in vivo electroporation for effective immunogenicity. Protection in mice was evaluated by challenge with transgenic P. berghei expressing PfCSP. In Balb/c mice, antibody responses and protective efficacy were both affected progressively with sequential deletion of C-terminal amino acid residues. Similar studies in C57Bl/6 mice revealed that immunizations with plasmids encoding truncated PfCSP showed partial protection from sporozoite challenge with no significant differences in antibody titers observed compared to full-length PfCSP DNA immunized mice. Further analysis revealed murine strain-specific differences in the recognition of specific epitopes.
Publisher
Elsevier Ltd,Elsevier Limited
Subject
/ Animals
/ Antibodies, Protozoan - immunology
/ Antigens
/ DNA
/ domain
/ Enzymes
/ Epitopes
/ Epitopes, B-Lymphocyte - genetics
/ Epitopes, B-Lymphocyte - immunology
/ Epitopes, T-Lymphocyte - genetics
/ Epitopes, T-Lymphocyte - immunology
/ Female
/ genetically modified organisms
/ Malaria
/ Malaria Vaccines - administration & dosage
/ Malaria Vaccines - immunology
/ Malaria, Falciparum - immunology
/ Malaria, Falciparum - prevention & control
/ Mice
/ Plasmids
/ Plasmodium falciparum - genetics
/ Plasmodium falciparum - immunology
/ Proteins
/ Protozoan Proteins - genetics
/ Protozoan Proteins - immunology
/ Vaccine
/ Vaccines
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