Discovery of Novel Plasmodium falciparum Pre-Erythrocytic Antigens for Vaccine Development
Nearly 100% protection against malaria infection can be achieved in humans by immunization with P. falciparum radiation-attenuated sporozoites (RAS). Although it is thought that protection is mediated by T cell and antibody responses, only a few of the many pre-erythrocytic (sporozoite and liver sta...
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| Published in | PloS one Vol. 10; no. 8; p. e0136109 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Public Library of Science
20.08.2015
Public Library of Science (PLoS) |
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| Online Access | Get full text |
| ISSN | 1932-6203 1932-6203 |
| DOI | 10.1371/journal.pone.0136109 |
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| Abstract | Nearly 100% protection against malaria infection can be achieved in humans by immunization with P. falciparum radiation-attenuated sporozoites (RAS). Although it is thought that protection is mediated by T cell and antibody responses, only a few of the many pre-erythrocytic (sporozoite and liver stage) antigens that are targeted by these responses have been identified.
Twenty seven P. falciparum pre-erythrocytic antigens were selected using bioinformatics analysis and expression databases and were expressed in a wheat germ cell-free protein expression system. Recombinant proteins were recognized by plasma from RAS-immunized subjects, and 21 induced detectable antibody responses in mice and rabbit and sera from these immunized animals were used to characterize these antigens. All 21 proteins localized to the sporozoite: five localized to the surface, seven localized to the micronemes, cytoplasm, endoplasmic reticulum or nucleus, two localized to the surface and cytoplasm, and seven remain undetermined. PBMC from RAS-immunized volunteers elicited positive ex vivo or cultured ELISpot responses against peptides from 20 of the 21 antigens.
These T cell and antibody responses support our approach of using reagents from RAS-immunized subjects to screen potential vaccine antigens, and have led to the identification of a panel of novel P. falciparum antigens. These results provide evidence to further evaluate these antigens as vaccine candidates.
ClinicalTrials.gov NCT00870987 ClinicalTrials.gov NCT00392015. |
|---|---|
| AbstractList | Background Nearly 100% protection against malaria infection can be achieved in humans by immunization with P. falciparum radiation-attenuated sporozoites (RAS). Although it is thought that protection is mediated by T cell and antibody responses, only a few of the many pre-erythrocytic (sporozoite and liver stage) antigens that are targeted by these responses have been identified. Methodology Twenty seven P. falciparum pre-erythrocytic antigens were selected using bioinformatics analysis and expression databases and were expressed in a wheat germ cell-free protein expression system. Recombinant proteins were recognized by plasma from RAS-immunized subjects, and 21 induced detectable antibody responses in mice and rabbit and sera from these immunized animals were used to characterize these antigens. All 21 proteins localized to the sporozoite: five localized to the surface, seven localized to the micronemes, cytoplasm, endoplasmic reticulum or nucleus, two localized to the surface and cytoplasm, and seven remain undetermined. PBMC from RAS-immunized volunteers elicited positive ex vivo or cultured ELISpot responses against peptides from 20 of the 21 antigens. Conclusions These T cell and antibody responses support our approach of using reagents from RAS-immunized subjects to screen potential vaccine antigens, and have led to the identification of a panel of novel P. falciparum antigens. These results provide evidence to further evaluate these antigens as vaccine candidates. Trial Registration ClinicalTrials.gov NCT00870987 ClinicalTrials.gov NCT00392015 Nearly 100% protection against malaria infection can be achieved in humans by immunization with P. falciparum radiation-attenuated sporozoites (RAS). Although it is thought that protection is mediated by T cell and antibody responses, only a few of the many pre-erythrocytic (sporozoite and liver stage) antigens that are targeted by these responses have been identified. Twenty seven P. falciparum pre-erythrocytic antigens were selected using bioinformatics analysis and expression databases and were expressed in a wheat germ cell-free protein expression system. Recombinant proteins were recognized by plasma from RAS-immunized subjects, and 21 induced detectable antibody responses in mice and rabbit and sera from these immunized animals were used to characterize these antigens. All 21 proteins localized to the sporozoite: five localized to the surface, seven localized to the micronemes, cytoplasm, endoplasmic reticulum or nucleus, two localized to the surface and cytoplasm, and seven remain undetermined. PBMC from RAS-immunized volunteers elicited positive ex vivo or cultured ELISpot responses against peptides from 20 of the 21 antigens. These T cell and antibody responses support our approach of using reagents from RAS-immunized subjects to screen potential vaccine antigens, and have led to the identification of a panel of novel P. falciparum antigens. These results provide evidence to further evaluate these antigens as vaccine candidates. Background Nearly 100% protection against malaria infection can be achieved in humans by immunization with P. falciparum radiation-attenuated sporozoites (RAS). Although it is thought that protection is mediated by T cell and antibody responses, only a few of the many pre-erythrocytic (sporozoite and liver stage) antigens that are targeted by these responses have been identified. Methodology Twenty seven P. falciparum pre-erythrocytic antigens were selected using bioinformatics analysis and expression databases and were expressed in a wheat germ cell-free protein expression system. Recombinant proteins were recognized by plasma from RAS-immunized subjects, and 21 induced detectable antibody responses in mice and rabbit and sera from these immunized animals were used to characterize these antigens. All 21 proteins localized to the sporozoite: five localized to the surface, seven localized to the micronemes, cytoplasm, endoplasmic reticulum or nucleus, two localized to the surface and cytoplasm, and seven remain undetermined. PBMC from RAS-immunized volunteers elicited positive ex vivo or cultured ELISpot responses against peptides from 20 of the 21 antigens. Conclusions These T cell and antibody responses support our approach of using reagents from RAS-immunized subjects to screen potential vaccine antigens, and have led to the identification of a panel of novel P. falciparum antigens. These results provide evidence to further evaluate these antigens as vaccine candidates. Trial Registration ClinicalTrials.gov NCT00870987 ClinicalTrials.gov NCT00392015 Nearly 100% protection against malaria infection can be achieved in humans by immunization with P. falciparum radiation-attenuated sporozoites (RAS). Although it is thought that protection is mediated by T cell and antibody responses, only a few of the many pre-erythrocytic (sporozoite and liver stage) antigens that are targeted by these responses have been identified.Twenty seven P. falciparum pre-erythrocytic antigens were selected using bioinformatics analysis and expression databases and were expressed in a wheat germ cell-free protein expression system. Recombinant proteins were recognized by plasma from RAS-immunized subjects, and 21 induced detectable antibody responses in mice and rabbit and sera from these immunized animals were used to characterize these antigens. All 21 proteins localized to the sporozoite: five localized to the surface, seven localized to the micronemes, cytoplasm, endoplasmic reticulum or nucleus, two localized to the surface and cytoplasm, and seven remain undetermined. PBMC from RAS-immunized volunteers elicited positive ex vivo or cultured ELISpot responses against peptides from 20 of the 21 antigens.These T cell and antibody responses support our approach of using reagents from RAS-immunized subjects to screen potential vaccine antigens, and have led to the identification of a panel of novel P. falciparum antigens. These results provide evidence to further evaluate these antigens as vaccine candidates.ClinicalTrials.gov NCT00870987 ClinicalTrials.gov NCT00392015. Nearly 100% protection against malaria infection can be achieved in humans by immunization with P. falciparum radiation-attenuated sporozoites (RAS). Although it is thought that protection is mediated by T cell and antibody responses, only a few of the many pre-erythrocytic (sporozoite and liver stage) antigens that are targeted by these responses have been identified. Twenty seven P. falciparum pre-erythrocytic antigens were selected using bioinformatics analysis and expression databases and were expressed in a wheat germ cell-free protein expression system. Recombinant proteins were recognized by plasma from RAS-immunized subjects, and 21 induced detectable antibody responses in mice and rabbit and sera from these immunized animals were used to characterize these antigens. All 21 proteins localized to the sporozoite: five localized to the surface, seven localized to the micronemes, cytoplasm, endoplasmic reticulum or nucleus, two localized to the surface and cytoplasm, and seven remain undetermined. PBMC from RAS-immunized volunteers elicited positive ex vivo or cultured ELISpot responses against peptides from 20 of the 21 antigens. These T cell and antibody responses support our approach of using reagents from RAS-immunized subjects to screen potential vaccine antigens, and have led to the identification of a panel of novel P. falciparum antigens. These results provide evidence to further evaluate these antigens as vaccine candidates. ClinicalTrials.gov NCT00870987 ClinicalTrials.gov NCT00392015. |
| Audience | Academic |
| Author | Wanga, Joyce Richie, Thomas L. Carucci, Daniel Sedegah, Martha Mazeika, Julie K. Hollingdale, Michael R. Iriko, Hideyuki Aguiar, Joao C. Sacci, John B. Hoffman, Stephen L. Villasante, Eileen D. Limbach, Keith Patterson, Noelle B. Bolton, Jessica Han, Eun-Taek Tsuboi, Takafumi Cruz, Ann-Marie |
| AuthorAffiliation | 7 EMD Millipore Corporation, North Andover, MA 01845, United States of America INSERM, FRANCE 5 Department of Microbiology and Immunology, The University of Maryland School of Medicine, Baltimore, MD 21201, United States of America 3 The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, United States of America 8 Department of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do 200-701, Republic of Korea 4 Technical Resources International, Inc., Bethesda, MD 20817, United States of America 9 PATH Malaria Vaccine Initiative, Washington, DC 20001, United States of America 10 Proteo-Science Center, Ehime University, Matsuyama, Ehime 790-8577, Japan 2 Camris International, Bethesda, MD 20814, United States of America 1 Malaria Department, Naval Medical Research Center, Silver Spring, MD 20910, United States of America 6 Department of International Health, Kobe University Graduate Sc |
| AuthorAffiliation_xml | – name: 5 Department of Microbiology and Immunology, The University of Maryland School of Medicine, Baltimore, MD 21201, United States of America – name: 4 Technical Resources International, Inc., Bethesda, MD 20817, United States of America – name: 9 PATH Malaria Vaccine Initiative, Washington, DC 20001, United States of America – name: 10 Proteo-Science Center, Ehime University, Matsuyama, Ehime 790-8577, Japan – name: 3 The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, United States of America – name: INSERM, FRANCE – name: 6 Department of International Health, Kobe University Graduate School of Health Science, Kobe 654-0142, Japan – name: 2 Camris International, Bethesda, MD 20814, United States of America – name: 8 Department of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do 200-701, Republic of Korea – name: 7 EMD Millipore Corporation, North Andover, MA 01845, United States of America – name: 1 Malaria Department, Naval Medical Research Center, Silver Spring, MD 20910, United States of America |
| Author_xml | – sequence: 1 givenname: Joao C. surname: Aguiar fullname: Aguiar, Joao C. – sequence: 2 givenname: Jessica surname: Bolton fullname: Bolton, Jessica – sequence: 3 givenname: Joyce surname: Wanga fullname: Wanga, Joyce – sequence: 4 givenname: John B. surname: Sacci fullname: Sacci, John B. – sequence: 5 givenname: Hideyuki surname: Iriko fullname: Iriko, Hideyuki – sequence: 6 givenname: Julie K. surname: Mazeika fullname: Mazeika, Julie K. – sequence: 7 givenname: Eun-Taek surname: Han fullname: Han, Eun-Taek – sequence: 8 givenname: Keith surname: Limbach fullname: Limbach, Keith – sequence: 9 givenname: Noelle B. surname: Patterson fullname: Patterson, Noelle B. – sequence: 10 givenname: Martha surname: Sedegah fullname: Sedegah, Martha – sequence: 11 givenname: Ann-Marie surname: Cruz fullname: Cruz, Ann-Marie – sequence: 12 givenname: Takafumi surname: Tsuboi fullname: Tsuboi, Takafumi – sequence: 13 givenname: Stephen L. surname: Hoffman fullname: Hoffman, Stephen L. – sequence: 14 givenname: Daniel surname: Carucci fullname: Carucci, Daniel – sequence: 15 givenname: Michael R. surname: Hollingdale fullname: Hollingdale, Michael R. – sequence: 16 givenname: Eileen D. surname: Villasante fullname: Villasante, Eileen D. – sequence: 17 givenname: Thomas L. surname: Richie fullname: Richie, Thomas L. |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/26292257$$D View this record in MEDLINE/PubMed |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 Conceived and designed the experiments: JCA. Performed the experiments: JCA JB JW JBS HI JKM E-TH. Analyzed the data: JCA JB JBS TT MRH. Contributed reagents/materials/analysis tools: JBS NBP TT MS. Wrote the paper: JCA NBP A-MC SLH MRH EDV TLR. Provided technical and scientific advice: KL SLH DC TLR. Established assays: MS. Competing Interests: JCA is an employee of Camris International. JW is an employee of Technical Resources International, Inc. JKM is an employee of EMD Millipore Corporation. There are no patents, products in development, or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials. Current address: Sanaria, 9800 Medical Center Drive, Suite A209, Rockville, MD 20850, United States of America |
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| Snippet | Nearly 100% protection against malaria infection can be achieved in humans by immunization with P. falciparum radiation-attenuated sporozoites (RAS). Although... Background Nearly 100% protection against malaria infection can be achieved in humans by immunization with P. falciparum radiation-attenuated sporozoites... Background Nearly 100% protection against malaria infection can be achieved in humans by immunization with P. falciparum radiation-attenuated sporozoites... |
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| Title | Discovery of Novel Plasmodium falciparum Pre-Erythrocytic Antigens for Vaccine Development |
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