Plasmodium falciparum Blood Stage Antimalarial Vaccines: An Analysis of Ongoing Clinical Trials and New Perspectives Related to Synthetic Vaccines

Plasmodium falciparum malaria is a disease causing high morbidity and mortality rates worldwide, mainly in sub-Saharan Africa. Candidates have been identified for vaccines targeting the parasite’s blood stage; this stage is important in the development of symptoms and clinical complications. However...

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Autores:
Tipo de recurso:
Fecha de publicación:
2019
Institución:
Universidad del Rosario
Repositorio:
Repositorio EdocUR - U. Rosario
Idioma:
eng
OAI Identifier:
oai:repository.urosario.edu.co:10336/24091
Acceso en línea:
https://doi.org/10.3389/fmicb.2019.02712
https://repository.urosario.edu.co/handle/10336/24091
Palabra clave:
Ama 1 dico vaccine
Ama1 dico vaccine
Bk se36 vaccine
Erythrocyte binding protein 175 r2 ng vaccine
Gmz2 vaccine
Malaria vaccine
Msp3 lsp vaccine
Mva rh5 vaccine
P27a vaccine
Pfpebs vaccine
Placental malaria vaccine
Recombinant vaccine
Unclassified drug
Virus vector
Bioinformatics
Conformational transition
Cytokine release
Dna polymorphism
Emulsion
Gene expression system
Growth inhibition
Human
Humoral immunity
Immune response
Immunization
Immunogenicity
Malaria falciparum
Nonhuman
Phase 1 clinical trial (topic)
Phase 2 clinical trial (topic)
Review
Seroconversion
Vaccination
Antimalarial vaccine
Clinical trial
Immunogenicity
Malaria
Merozoite
Plasmodium falciparum
Vaccine
Rights
License
Abierto (Texto Completo)
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dc.title.spa.fl_str_mv Plasmodium falciparum Blood Stage Antimalarial Vaccines: An Analysis of Ongoing Clinical Trials and New Perspectives Related to Synthetic Vaccines
title Plasmodium falciparum Blood Stage Antimalarial Vaccines: An Analysis of Ongoing Clinical Trials and New Perspectives Related to Synthetic Vaccines
spellingShingle Plasmodium falciparum Blood Stage Antimalarial Vaccines: An Analysis of Ongoing Clinical Trials and New Perspectives Related to Synthetic Vaccines
Ama 1 dico vaccine
Ama1 dico vaccine
Bk se36 vaccine
Erythrocyte binding protein 175 r2 ng vaccine
Gmz2 vaccine
Malaria vaccine
Msp3 lsp vaccine
Mva rh5 vaccine
P27a vaccine
Pfpebs vaccine
Placental malaria vaccine
Recombinant vaccine
Unclassified drug
Virus vector
Bioinformatics
Conformational transition
Cytokine release
Dna polymorphism
Emulsion
Gene expression system
Growth inhibition
Human
Humoral immunity
Immune response
Immunization
Immunogenicity
Malaria falciparum
Nonhuman
Phase 1 clinical trial (topic)
Phase 2 clinical trial (topic)
Review
Seroconversion
Vaccination
Antimalarial vaccine
Clinical trial
Immunogenicity
Malaria
Merozoite
Plasmodium falciparum
Vaccine
title_short Plasmodium falciparum Blood Stage Antimalarial Vaccines: An Analysis of Ongoing Clinical Trials and New Perspectives Related to Synthetic Vaccines
title_full Plasmodium falciparum Blood Stage Antimalarial Vaccines: An Analysis of Ongoing Clinical Trials and New Perspectives Related to Synthetic Vaccines
title_fullStr Plasmodium falciparum Blood Stage Antimalarial Vaccines: An Analysis of Ongoing Clinical Trials and New Perspectives Related to Synthetic Vaccines
title_full_unstemmed Plasmodium falciparum Blood Stage Antimalarial Vaccines: An Analysis of Ongoing Clinical Trials and New Perspectives Related to Synthetic Vaccines
title_sort Plasmodium falciparum Blood Stage Antimalarial Vaccines: An Analysis of Ongoing Clinical Trials and New Perspectives Related to Synthetic Vaccines
dc.subject.keyword.spa.fl_str_mv Ama 1 dico vaccine
Ama1 dico vaccine
Bk se36 vaccine
Erythrocyte binding protein 175 r2 ng vaccine
Gmz2 vaccine
Malaria vaccine
Msp3 lsp vaccine
Mva rh5 vaccine
P27a vaccine
Pfpebs vaccine
Placental malaria vaccine
Recombinant vaccine
Unclassified drug
Virus vector
Bioinformatics
Conformational transition
Cytokine release
Dna polymorphism
Emulsion
Gene expression system
Growth inhibition
Human
Humoral immunity
Immune response
Immunization
Immunogenicity
Malaria falciparum
Nonhuman
Phase 1 clinical trial (topic)
Phase 2 clinical trial (topic)
Review
Seroconversion
Vaccination
Antimalarial vaccine
Clinical trial
Immunogenicity
Malaria
Merozoite
Plasmodium falciparum
Vaccine
topic Ama 1 dico vaccine
Ama1 dico vaccine
Bk se36 vaccine
Erythrocyte binding protein 175 r2 ng vaccine
Gmz2 vaccine
Malaria vaccine
Msp3 lsp vaccine
Mva rh5 vaccine
P27a vaccine
Pfpebs vaccine
Placental malaria vaccine
Recombinant vaccine
Unclassified drug
Virus vector
Bioinformatics
Conformational transition
Cytokine release
Dna polymorphism
Emulsion
Gene expression system
Growth inhibition
Human
Humoral immunity
Immune response
Immunization
Immunogenicity
Malaria falciparum
Nonhuman
Phase 1 clinical trial (topic)
Phase 2 clinical trial (topic)
Review
Seroconversion
Vaccination
Antimalarial vaccine
Clinical trial
Immunogenicity
Malaria
Merozoite
Plasmodium falciparum
Vaccine
description Plasmodium falciparum malaria is a disease causing high morbidity and mortality rates worldwide, mainly in sub-Saharan Africa. Candidates have been identified for vaccines targeting the parasite’s blood stage; this stage is important in the development of symptoms and clinical complications. However, no vaccine that can directly affect morbidity and mortality rates is currently available. This review analyzes the formulation, methodological design, and results of active clinical trials for merozoite-stage vaccines, regarding their safety profile, immunological response (phase Ia/Ib), and protective efficacy levels (phase II). Most vaccine candidates are in phase I trials and have had an acceptable safety profile. GMZ2 has made the greatest progress in clinical trials; its efficacy has been 14% in children aged less than 5 years in a phase IIb trial. Most of the available candidates that have shown strong immunogenicity and that have been tested for their protective efficacy have provided good results when challenged with a homologous parasite strain; however, their efficacy has dropped when they have been exposed to a heterologous strain. In view of these vaccines’ unpromising results, an alternative approach for selecting new candidates is needed; such line of work should be focused on how to increase an immune response induced against the highly conserved (i.e., common to all strains), functionally relevant, protein regions that the parasite uses to invade target cells. Despite binding regions tending to be conserved, they are usually poorly antigenic and/or immunogenic, being frequently discarded as vaccine candidates when the conventional immunological approach is followed. The Fundación Instituto de Inmunología de Colombia (FIDIC) has developed a logical and rational methodology based on including conserved high-activity binding peptides (cHABPs) from the main P. falciparum biologically functional proteins involved in red blood cell (RBC) invasion. Once appropriately modified (mHABPs), these minimal, subunit-based, chemically synthesized peptides can be used in a system covering the human immune system’s main genetic variables (the human leukocyte antigen HLA-DR isotype) inducing a suitable, immunogenic, and protective immune response in most of the world’s populations. © Copyright © 2019 Salamanca, Gómez, Camargo, Cuy-Chaparro, Molina-Franky, Reyes, Patarroyo and Patarroyo.
publishDate 2019
dc.date.created.spa.fl_str_mv 2019
dc.date.accessioned.none.fl_str_mv 2020-05-26T00:08:31Z
dc.date.available.none.fl_str_mv 2020-05-26T00:08:31Z
dc.type.eng.fl_str_mv article
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dc.type.spa.spa.fl_str_mv Artículo
dc.identifier.doi.none.fl_str_mv https://doi.org/10.3389/fmicb.2019.02712
dc.identifier.issn.none.fl_str_mv 1664302X
dc.identifier.uri.none.fl_str_mv https://repository.urosario.edu.co/handle/10336/24091
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dc.relation.citationTitle.none.fl_str_mv Frontiers in Microbiology
dc.relation.citationVolume.none.fl_str_mv Vol. 10
dc.relation.ispartof.spa.fl_str_mv Frontiers in Microbiology, ISSN:1664302X, Vol.10,(2019)
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spelling 41bedf0b-35c8-4f78-884f-769f65f3f007-14e9a295b-a84c-4a61-8d2f-40ad823a34fe-13b7490f7-a153-437b-aba0-f5692e5bde64-14583a3bd-8b6b-4c00-903b-8afc253255fb-1ab9816de-63e2-4cc8-bf37-73bf0b8e9c5c-153332dc1-6365-41c0-8bf2-a42d23dcc8fc-19e3ba9df-fe89-48fe-9521-cc8f452d56f5-1796530656002020-05-26T00:08:31Z2020-05-26T00:08:31Z2019Plasmodium falciparum malaria is a disease causing high morbidity and mortality rates worldwide, mainly in sub-Saharan Africa. Candidates have been identified for vaccines targeting the parasite’s blood stage; this stage is important in the development of symptoms and clinical complications. However, no vaccine that can directly affect morbidity and mortality rates is currently available. This review analyzes the formulation, methodological design, and results of active clinical trials for merozoite-stage vaccines, regarding their safety profile, immunological response (phase Ia/Ib), and protective efficacy levels (phase II). Most vaccine candidates are in phase I trials and have had an acceptable safety profile. GMZ2 has made the greatest progress in clinical trials; its efficacy has been 14% in children aged less than 5 years in a phase IIb trial. Most of the available candidates that have shown strong immunogenicity and that have been tested for their protective efficacy have provided good results when challenged with a homologous parasite strain; however, their efficacy has dropped when they have been exposed to a heterologous strain. In view of these vaccines’ unpromising results, an alternative approach for selecting new candidates is needed; such line of work should be focused on how to increase an immune response induced against the highly conserved (i.e., common to all strains), functionally relevant, protein regions that the parasite uses to invade target cells. Despite binding regions tending to be conserved, they are usually poorly antigenic and/or immunogenic, being frequently discarded as vaccine candidates when the conventional immunological approach is followed. The Fundación Instituto de Inmunología de Colombia (FIDIC) has developed a logical and rational methodology based on including conserved high-activity binding peptides (cHABPs) from the main P. falciparum biologically functional proteins involved in red blood cell (RBC) invasion. Once appropriately modified (mHABPs), these minimal, subunit-based, chemically synthesized peptides can be used in a system covering the human immune system’s main genetic variables (the human leukocyte antigen HLA-DR isotype) inducing a suitable, immunogenic, and protective immune response in most of the world’s populations. © Copyright © 2019 Salamanca, Gómez, Camargo, Cuy-Chaparro, Molina-Franky, Reyes, Patarroyo and Patarroyo.application/pdfhttps://doi.org/10.3389/fmicb.2019.027121664302Xhttps://repository.urosario.edu.co/handle/10336/24091engFrontiers Media S.A.Frontiers in MicrobiologyVol. 10Frontiers in Microbiology, ISSN:1664302X, Vol.10,(2019)https://www.scopus.com/inward/record.uri?eid=2-s2.0-85076945544&doi=10.3389%2ffmicb.2019.02712&partnerID=40&md5=5c72db0f3d6039db49883eead08f426aAbierto (Texto Completo)http://purl.org/coar/access_right/c_abf2instname:Universidad del Rosarioreponame:Repositorio Institucional EdocURAma 1 dico vaccineAma1 dico vaccineBk se36 vaccineErythrocyte binding protein 175 r2 ng vaccineGmz2 vaccineMalaria vaccineMsp3 lsp vaccineMva rh5 vaccineP27a vaccinePfpebs vaccinePlacental malaria vaccineRecombinant vaccineUnclassified drugVirus vectorBioinformaticsConformational transitionCytokine releaseDna polymorphismEmulsionGene expression systemGrowth inhibitionHumanHumoral immunityImmune responseImmunizationImmunogenicityMalaria falciparumNonhumanPhase 1 clinical trial (topic)Phase 2 clinical trial (topic)ReviewSeroconversionVaccinationAntimalarial vaccineClinical trialImmunogenicityMalariaMerozoitePlasmodium falciparumVaccinePlasmodium falciparum Blood Stage Antimalarial Vaccines: An Analysis of Ongoing Clinical Trials and New Perspectives Related to Synthetic VaccinesarticleArtículohttp://purl.org/coar/version/c_970fb48d4fbd8a85http://purl.org/coar/resource_type/c_6501Salamanca, David RicardoGómez, MarcelaCamargo, AnnyCuy-Chaparro, LauraMolina-Franky, JessicaReyes, CésarPatarroyo, Manuel ElkinPatarroyo, Manuel A.ORIGINALfmicb-10-02712.pdfapplication/pdf3106506https://repository.urosario.edu.co/bitstreams/e4f27273-a3f7-4bbe-8256-5a42b5b7b37c/download7de6231a7a4e95fe75240fc98fbe949eMD51TEXTfmicb-10-02712.pdf.txtfmicb-10-02712.pdf.txtExtracted texttext/plain84731https://repository.urosario.edu.co/bitstreams/5ca38e1e-6000-4fd0-bddd-cb6282436d4c/download2e0aaa510ceab94ea1097aa98ff28a98MD52THUMBNAILfmicb-10-02712.pdf.jpgfmicb-10-02712.pdf.jpgGenerated Thumbnailimage/jpeg4617https://repository.urosario.edu.co/bitstreams/5c5a4d34-bbf7-4c2b-97a1-47f877c2126f/download30ed4c094090892ea2a1ce0318afb84dMD5310336/24091oai:repository.urosario.edu.co:10336/240912022-05-02 07:37:21.39511https://repository.urosario.edu.coRepositorio institucional EdocURedocur@urosario.edu.co