Association of antibodies to Plasmodium falciparum Reticulocyte Binding Protein Homologue 5 with protection from clinical malaria
Emerging evidence suggests that antibodies against merozoite proteins involved in P. falciparum invasion into the red blood cell (RBC) play an important role in clinical immunity to malaria. The protein family of parasite antigens known as P. falciparum Reticulocyte Binding Protein Homologue (PfRh)...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2014-06-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fmicb.2014.00314/full |
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| author | Chris Y. H. Chiu Chris Y. H. Chiu Julie eHealer Jennifer K. Thompson Lin eChen Aiki eKaul Laxman eSavergave Arjun eRaghuwanshi Connie S. N, Li Wai Suen Peter M. Siba Louis eSchofield Louis eSchofield Ivo eMueller Ivo eMueller Alan F Cowman Alan F Cowman Diana Silvia Hansen Diana Silvia Hansen |
| author_facet | Chris Y. H. Chiu Chris Y. H. Chiu Julie eHealer Jennifer K. Thompson Lin eChen Aiki eKaul Laxman eSavergave Arjun eRaghuwanshi Connie S. N, Li Wai Suen Peter M. Siba Louis eSchofield Louis eSchofield Ivo eMueller Ivo eMueller Alan F Cowman Alan F Cowman Diana Silvia Hansen Diana Silvia Hansen |
| author_sort | Chris Y. H. Chiu |
| collection | DOAJ |
| description | Emerging evidence suggests that antibodies against merozoite proteins involved in P. falciparum invasion into the red blood cell (RBC) play an important role in clinical immunity to malaria. The protein family of parasite antigens known as P. falciparum Reticulocyte Binding Protein Homologue (PfRh) is required for RBC invasion. PfRh5 is the only member within the PfRh family that cannot be genetically deleted, suggesting it plays an essential role in parasite survival. This antigen forms a complex with the cysteine-rich P. falciparum Rh5 interacting protein (PfRipr), on the merozoite surface during RBC invasion. The PfRh5 ectodomain sequence and a C-terminal fragment of PfRipr were cloned and expressed in E. coli and baculovirus-infected cells respectively. Immunization of rabbits with these recombinant proteins induced antibodies able to inhibit growth of various P. falciparum strains. Antibody responses to these proteins were investigated in a treatment-re-infection study conducted in an endemic area of Papua New Guinea (PNG) to determine their contribution to naturally acquired immunity. Antibody titres to PfRh5 but not PfRipr showed strong association with protection against P. falciparum clinical episodes. When associations with time to first infection were analysed, high antibody levels against PfRh5 were also found to be associated with protection from high-density infections but not from re-infection. Together these results indicate that PfRh5 is an important target of protective immunity and constitutes a promising vaccine candidate. |
| first_indexed | 2024-12-13T21:57:50Z |
| format | Article |
| id | doaj.art-c14f84b2786042c2acccabc22bc2382a |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-13T21:57:50Z |
| publishDate | 2014-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Microbiology |
| spelling | doaj.art-c14f84b2786042c2acccabc22bc2382a2022-12-21T23:30:06ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2014-06-01510.3389/fmicb.2014.0031499462Association of antibodies to Plasmodium falciparum Reticulocyte Binding Protein Homologue 5 with protection from clinical malariaChris Y. H. Chiu0Chris Y. H. Chiu1Julie eHealer2Jennifer K. Thompson3Lin eChen4Aiki eKaul5Laxman eSavergave6Arjun eRaghuwanshi7Connie S. N, Li Wai Suen8Peter M. Siba9Louis eSchofield10Louis eSchofield11Ivo eMueller12Ivo eMueller13Alan F Cowman14Alan F Cowman15Diana Silvia Hansen16Diana Silvia Hansen17The Walter and Eliza Hall Institute of Medical ResearchThe University of MelbourneThe Walter and Eliza Hall Institute of Medical ResearchThe Walter and Eliza Hall Institute of Medical ResearchThe Walter and Eliza Hall Institute of Medical ResearchGennova PharmaceuticalsGennova PharmaceuticalsGennova PharmaceuticalsThe Walter and Eliza Hall Institute of Medical ResearchPapua New Guinea Institute of Medical ResearchThe Walter and Eliza Hall Institute of Medical ResearchJames Cook UniversityThe Walter and Eliza Hall Institute of Medical ResearchUniversity of Barcelona, BarcelonaThe Walter and Eliza Hall Institute of Medical ResearchThe University of MelbourneThe Walter and Eliza Hall Institute of Medical ResearchThe University of MelbourneEmerging evidence suggests that antibodies against merozoite proteins involved in P. falciparum invasion into the red blood cell (RBC) play an important role in clinical immunity to malaria. The protein family of parasite antigens known as P. falciparum Reticulocyte Binding Protein Homologue (PfRh) is required for RBC invasion. PfRh5 is the only member within the PfRh family that cannot be genetically deleted, suggesting it plays an essential role in parasite survival. This antigen forms a complex with the cysteine-rich P. falciparum Rh5 interacting protein (PfRipr), on the merozoite surface during RBC invasion. The PfRh5 ectodomain sequence and a C-terminal fragment of PfRipr were cloned and expressed in E. coli and baculovirus-infected cells respectively. Immunization of rabbits with these recombinant proteins induced antibodies able to inhibit growth of various P. falciparum strains. Antibody responses to these proteins were investigated in a treatment-re-infection study conducted in an endemic area of Papua New Guinea (PNG) to determine their contribution to naturally acquired immunity. Antibody titres to PfRh5 but not PfRipr showed strong association with protection against P. falciparum clinical episodes. When associations with time to first infection were analysed, high antibody levels against PfRh5 were also found to be associated with protection from high-density infections but not from re-infection. Together these results indicate that PfRh5 is an important target of protective immunity and constitutes a promising vaccine candidate.http://journal.frontiersin.org/Journal/10.3389/fmicb.2014.00314/fullAntibodiesImmunityMalariaPlasmodium falciparumReticulocyte Binding proteing homologue 5 |
| spellingShingle | Chris Y. H. Chiu Chris Y. H. Chiu Julie eHealer Jennifer K. Thompson Lin eChen Aiki eKaul Laxman eSavergave Arjun eRaghuwanshi Connie S. N, Li Wai Suen Peter M. Siba Louis eSchofield Louis eSchofield Ivo eMueller Ivo eMueller Alan F Cowman Alan F Cowman Diana Silvia Hansen Diana Silvia Hansen Association of antibodies to Plasmodium falciparum Reticulocyte Binding Protein Homologue 5 with protection from clinical malaria Frontiers in Microbiology Antibodies Immunity Malaria Plasmodium falciparum Reticulocyte Binding proteing homologue 5 |
| title | Association of antibodies to Plasmodium falciparum Reticulocyte Binding Protein Homologue 5 with protection from clinical malaria |
| title_full | Association of antibodies to Plasmodium falciparum Reticulocyte Binding Protein Homologue 5 with protection from clinical malaria |
| title_fullStr | Association of antibodies to Plasmodium falciparum Reticulocyte Binding Protein Homologue 5 with protection from clinical malaria |
| title_full_unstemmed | Association of antibodies to Plasmodium falciparum Reticulocyte Binding Protein Homologue 5 with protection from clinical malaria |
| title_short | Association of antibodies to Plasmodium falciparum Reticulocyte Binding Protein Homologue 5 with protection from clinical malaria |
| title_sort | association of antibodies to plasmodium falciparum reticulocyte binding protein homologue 5 with protection from clinical malaria |
| topic | Antibodies Immunity Malaria Plasmodium falciparum Reticulocyte Binding proteing homologue 5 |
| url | http://journal.frontiersin.org/Journal/10.3389/fmicb.2014.00314/full |
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