Now showing items 1-17 of 17

Behavior and abundance of Anopheles darlingi in communities living in the Colombian Amazon riverside

Prado, César Camilo; Alvarado Cabrera, Luis Antonio; Camargo Ayala, Paola Andrea; Garzón Ospina, Diego; Camargo, Milena; Soto-De León, Sara Cecilia; Cubides, Ricardo; Celis-Giraldo, Carmen Teresa; Patarroyo, Manuel Elkin; Patarroyo, Manuel Alfonso (2019)

In the past few years, relative frequencies of malaria parasite species in communities living in the Colombian Amazon riverside have changed, being Plasmodium vivax (61.4%) and Plasmodium malariae (43.8%) the most frequent. ...
Conserved binding regions provide the clue for peptide-based vaccine development: A chemical perspective

Curtidor, Hernando; Reyes, César; Bermúdez, Adriana; Vanegas, Magnolia; Varela, Yahson; Patarrollo, Manuel Elkin (2017)

Abstract: Synthetic peptides have become invaluable biomedical research and medicinal chemistry tools for studying functional roles, i.e., binding or proteolytic activity, naturally-occurring regions’ immunogenicity in ...
Easy and fast method for expression and native extraction of Plasmodium vivax Duffy binding protein fragments

Moreno Pérez, Darwin Andrés; Baquero, Luis Alfredo; Bermúdez, Maritza; Gómez Muñoz, Laura Alejandra; Varela, Yahson; Patarroyo, Manuel Alfonso (2018)

Background: The Plasmodium vivax Duffy binding protein (PvDBP) has been the most studied ligand binding human reticulocytes to date. This molecule has a cysteine-rich domain in region II (RII) which has been used as control ...
Malaria: Paving the way to developing peptide-based vaccines against invasion in infectious diseases

Reyes, César; Molina Franky, Jessica S.; Aza Conde, Jorge; Suárez, Carlos F.; Pabón, Laura; Moreno Vranich, Armando; Patarroyo, Manuel A.; Patarroyo, Manuel Elkin (2020)

Malaria remains a large-scale public health problem, killing more than 400,000 people and infecting up to 230 million worldwide, every year. Unfortunately, despite numerous efforts and research concerning vaccine development, ...
Micro-epidemiology of mixed-species malaria infections in a rural population living in the Colombian Amazon region

Camargo, Milena; Soto De León, Sara C.; Del Río Ospina, Luisa; Páez, Asrtid C.; González, Zanony; González, Edgardo.; Cubides, Juan R.; Camargo Ayala, Paola A.; Patarroyo, Manuel E.; Patarroyo, Manuel A. (2018)

Malaria outbreaks have been reported in recent years in the Colombian Amazon region, malaria has been re-emerging in areas where it was previously controlled. Information from malaria transmission networks and knowledge ...
On the evolution and function of Plasmodium vivax reticulocyte binding surface antigen (pvrbsa)

Camargo Ayala, P.A; Garzón Ospina, D.; Moreno Pérez, D.A.; Ricaurte Contreras, L.A.; Noya, O.; Patarroyo, M.A. (2018)

The RBSA protein is encoded by a gene described in Plasmodium species having tropism for reticulocytes. Since this protein is antigenic in natural infections and can bind to target cells, it has been proposed as a potential ...
Plasmodium falciparum pre-erythrocytic stage vaccine development

Molina Franky, Jessica; Cuy Chaparro, Laura; Camargo, Anny; Reyes, César; Gómez, Marcela; Salamanca, David Ricardo; Patarroyo, Manuel Alfonso; Patarroyo, Manuel Elkin (2020)

Worldwide strategies between 2010 and 2017 aimed at controlling malarial parasites (mainly Plasmodium falciparum) led to a reduction of just 18% regarding disease incidence rates. Many biologically-derived anti-malarial ...
Plasmodium vivax in vitro continuous culture: The spoke in the wheel

Bermúdez, Maritza; Moreno Pérez, Darwin Andrés; Arévalo Pinzón, Gabriela; Curtidor, Hernando; Patarroyo, Manuel A. (2018)

Understanding the life cycle of Plasmodium vivax is fundamental for developing strategies aimed at controlling and eliminating this parasitic species. Although advances in omic sciences and high-throughput techniques in ...
Plasmodium vivax Pv12 B-cell epitopes and HLA-DRβ1-dependent T-cell epitopes in vitro antigenicity

Yepes Pérez, Yoelis; López, Carolina; Suárez, Carlos F.; Patarroyo, Manuel A. (2018)

Malaria is an infectious disease caused by parasites from the genus Plasmodium (P. falciparum and P. vivax are responsible for 90% of all clinical cases); it is widely distributed throughout the world’s tropical and ...
Preliminary Evaluation of the Safety and Immunogenicity of an Antimalarial Vaccine Candidate Modified Peptide (IMPIPS) Mixture in a Murine Model

Lambraño, Jennifer; Curtidor, Hernando; Avendaño, Catalina; Díaz Arévalo, Diana; Roa, Leonardo; Vanegas, Magnolia; Patarroyo, Manuel Elkin; Patarroyo, Manuel A. (2019)

Malaria continues being a high-impact disease regarding public health worldwide; the WHO report for malaria in 2018 estimated that 219 million cases occurred in 2017, mostly caused by the parasite Plasmodium falciparum. ...
Self-assembling functional programmable protein array for studying protein-protein interactions in malaria parasites

Arévalo Pinzón, Gabriela; González González, María; Suárez, Carlos Fernando; Curtidor, Hernando; Carabias Sánchez, Javier; Muro, Antonio; LaBaer, Joshua; Patarroyo, Manuel Alfonso; Fuentes, Manuel (2018)

Background: Plasmodium vivax is the most widespread malarial species, causing significant morbidity worldwide. Knowledge is limited regarding the molecular mechanism of invasion due to the lack of a continuous in vitro ...
Sexual forms obtained in a continuous in vitro cultured Colombian strain of Plasmodium falciparum (FCB2)

Ararat Sarria, Monica; Prado, Cesar Camilo; Camargo, Milena; Ospina, Laura Tatiana; Camargo, Paola Andrea; Curtidor, Hernando; Patarroyo, Manuel Alfonso (2020)

Background: The epidemiological control of malaria has been hampered by the appearance of parasite resistance to anti-malarial drugs and by the resistance of mosquito vectors to control measures. This has also been associated ...
Structural analysis of owl monkey MHC-DR shows that fully-protective malaria vaccine components can be readily used in humans

Suárez, Carlos F.; Pabón, Laura; Barrera, Ana; Aza Conde, Jorge; Patarroyo, Manuel Alfonso; Patarroyo, Manuel Elkin (2017)

More than 50 years ago the owl monkey (genusAotus) was found to be highly susceptible to developinghuman malaria, making it an excellent experimental model for this disease. Microbes and parasites'(especially malaria) ...
TCR-contacting residues orientation and HLA-DRβ* binding preference determine long-lasting protective immunity against malaria

Alba, Martha P.; Suarez, Carlos F.; Varela, Yahson; Patarroyo, Manuel A.; Bermudez, Adriana; Patarroyo, Manuel Elkin (2016)

Fully-protective, long-lasting, immunological (FPLLI) memory against Plasmodium falciparum malaria regarding immune protection-inducing protein structures (IMPIPS) vaccinated into monkeys previously challenged and re-challenged ...
The in vitro antigenicity of Plasmodium vivax rhoptry neck protein 2 (PvRON2) B- and T-epitopes selected by HLA-DRB1 binding profile

López, Carolina; Yepes Pérez, Yoelis; Díaz Arévalo, Diana; Patarroyo, Manuel E.; Patarroyo, Manuel A. (2018)

Malaria caused by Plasmodium vivax is a neglected disease which is responsible for the highest morbidity in both Americas and Asia. Despite continuous public health efforts to prevent malarial infection, an effective ...
The role of pi-interactions and hydrogen bonds in fully protective synthetic malaria vaccine development

Reyes, César; Moreno-Vranich, Armando; Patarroyo, Manuel Elkin (2017)

Analysis of ourPlasmodium falciparummalaria parasite peptides'1H-NMR database in the search for H-bonds andp-interactions led us to correlate their presence or absence with a peptide's particularimmunological behavior. It ...
What Is Known about the Immune Response Induced by Plasmodium vivax Malaria Vaccine Candidates?

López, Carolina; Yepes Pérez, Yoelis; Hincapie Escobar, Natalia; Díaz-Arévalo, Diana; Patarroyo, Manuel A. (2017)

Malaria caused by Plasmodium vivax continues being one of the most important infectious diseases around the world; P. vivax is the second most prevalent species and has the greatest geographic distribution. Developing an ...

Envíos recientes

Behavior and abundance of Anopheles darlingi in communities living in the Colombian Amazon riverside
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Prado, César Camilo | 2019

In the past few years, relative frequencies of malaria parasite species in communities living in the Colombian Amazon riverside have changed, being Plasmodium vivax (61.4%) and Plasmodium malariae (43.8%) the most frequent. Given this epidemiological scenario, it is important to determine the species of anophelines involved in these parasites’ transmission. This study was carried out in June 2016 in two indigenous communities living close to the tributaries of the Amazon River using protected human bait. The results of this study showed a total abundance of 1,085 mosquitos, of which 99.2% corresponded to Anopheles darlingi. Additionally, only two anopheline species were found, showing low diversity in the study areas. Molecular confirmation of some individuals was then followed by evolutionary analysis by using the COI gene. Nested PCR was used for identifying the three Plasmodium species circulating in the study areas. Of the two species collected in this study, 21.0% of the An. darlingi mosquitoes were infected with P. malariae, 21.9% with P. vivax and 10.3% with Plasmodium falciparum. It exhibited exophilic and exophagic behavior in both study areas, having marked differences regarding its abundance in each community (Tipisca first sampling 49.4%, Tipisca second sampling 39.6% and Doce de Octubre 10.9%). Interestingly, An. mattogrossensis infected by P. vivax was found for the first time in Colombia (in 50% of the four females collected). Analysis of An. darlingi COI gene diversity indicated a single population maintaining a high gene flow between the study areas. The An. darlingi behavior pattern found in both communities represents a risk factor for the region’s inhabitants living/working near these sites. This highlights the need for vector control efforts such as the use of personal repellents and insecticides for use on cattle, which must be made available in order to reduce this Anopheline’s abundance.

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Conserved binding regions provide the clue for peptide-based vaccine development: A chemical perspective
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Curtidor, Hernando | 2017

Abstract: Synthetic peptides have become invaluable biomedical research and medicinal chemistry tools for studying functional roles, i.e., binding or proteolytic activity, naturally-occurring regions’ immunogenicity in proteins and developing therapeutic agents and vaccines. Synthetic peptides can mimic protein sites; their structure and function can be easily modulated by specific amino acid replacement. They have major advantages, i.e., they are cheap, easily-produced and chemically stable, lack infectious and secondary adverse reactions and can induce immune responses via T- and B-cell epitopes. Our group has previously shown that using synthetic peptides and adopting a functional approach has led to identifying Plasmodium falciparum conserved regions binding to host cells. Conserved high activity binding peptides’ (cHABPs) physicochemical, structural and immunological characteristics have been taken into account for properly modifying and converting them into highly immunogenic, protection-inducing peptides (mHABPs) in the experimental Aotus monkey model. This article describes stereo–electron and topochemical characteristics regarding major histocompatibility complex (MHC)-mHABP-T-cell receptor (TCR) complex formation. Some mHABPs in this complex inducing long-lasting, protective immunity have been named immune protection-inducing protein structures (IMPIPS), forming the subunit components in chemically synthesized vaccines. This manuscript summarizes this particular field and adds our recent findings concerning intramolecular interactions (H-bonds or π-interactions) enabling proper IMPIPS structure as well as the peripheral flanking residues (PFR) to stabilize the MHCII-IMPIPS-TCR interaction, aimed at inducing long-lasting, protective immunological memory

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Easy and fast method for expression and native extraction of Plasmodium vivax Duffy binding protein fragments
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Moreno Pérez, Darwin Andrés | 2018

Background: The Plasmodium vivax Duffy binding protein (PvDBP) has been the most studied ligand binding human reticulocytes to date. This molecule has a cysteine-rich domain in region II (RII) which has been used as control for evaluating the target cell binding activity of several parasite molecules. However, obtaining rPvDBP-RII in a soluble form using the Escherichia coli expression system usually requires laborious and time-consuming steps for recovering the molecule's structure and function, considering it is extracted from inclusion bodies. The present study describes an easy and fast method for expressing and obtaining several PvDBP fragments which should prove ideal for use in protein-cell interaction assays. Results: Two PvDBP encoding regions (rii and riii/v) were cloned in pEXP5-CT vector and expressed in E. coli and extracted from the soluble fraction (rPvDBP-RIIS and rPvDBP-RIII/VS) using a simple freezing/thawing protocol. After the purification, dichroism analysis enabled verifying high rPvDBP-RIIS and rPvDBP-RIII/VS secondary structure α-helix content, which was lowered when molecules were extracted from inclusion bodies (rPvDBP-RIIIB and rPvDBP-RIII/VIB) using a denaturing step. Interestingly, rPvDBP-RIIS, but not rPvDBP-RIIIB, bound to human reticulocytes, while rPvDBP-RIII/VS and rPvDBP-RIII/VIB bound to such cells in a similar way to negative control (cells incubated without recombinant proteins). Conclusions: This research has shown for the first time how rPvDBP-RII can be expressed and obtained in soluble form using the E. coli system and avoiding the denaturation and refolding steps commonly used. The results highlight the usefulness of the rPvDBP-RIII/VS fragment as a non-binding control for protein-cell target interaction assays. The soluble extraction protocol described is a good alternative to obtain fully functional P. vivax proteins in a fast and easy way, which will surely prove useful to laboratories working in studying this parasite's biology.

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Malaria: Paving the way to developing peptide-based vaccines against invasion in infectious diseases
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Reyes, César | 2020

Malaria remains a large-scale public health problem, killing more than 400,000 people and infecting up to 230 million worldwide, every year. Unfortunately, despite numerous efforts and research concerning vaccine development, results to date have been low and/or strain-specific. This work describes a strategy involving Plasmodium falciparum Duffy binding-like (DBL) and reticulocyte-binding protein homologue (RH) family-derived minimum functional peptides, netMHCIIpan3.2 parental and modified peptides’ in silico binding prediction and modeling some Aotus major histocompatibility class II (MHCII) molecules based on known human molecules’ structure to understand their differences. These are used to explain peptides’ immunological behaviour when used as vaccine components in the Aotus model. Despite the great similarity between human and Aotus immune system molecules, around 50% of Aotus allele molecules lack a counterpart in the human immune system which could lead to an Aotus-specific vaccine. It was also confirmed that functional Plasmodium falciparum’ conserved proteins are immunologically silent (in both the animal model and in-silico prediction); they must therefore be modified to elicit an appropriate immune response. Some peptides studied here had the desired behaviour and can thus be considered components of a fully-protective antimalarial vaccine.

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Micro-epidemiology of mixed-species malaria infections in a rural population living in the Colombian Amazon region
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Camargo, Milena | 2018

Malaria outbreaks have been reported in recent years in the Colombian Amazon region, malaria has been re-emerging in areas where it was previously controlled. Information from malaria transmission networks and knowledge about the population characteristics influencing the dispersal of parasite species is limited. This study aimed to determine the distribution patterns of Plasmodium vivax, P. malariae and P. falciparum single and mixed infections, as well as the significant socio-spatial groupings relating to the appearance of such infections. An active search in 57 localities resulted in 2,106 symptomatic patients being enrolled. Parasitaemia levels were assessed by optical microscopy, and parasites were detected by PCR. The association between mixed infections (in 43.2% of the population) and socio-spatial factors was modelled using logistic regression and multiple correspondence analyses. P. vivax occurred most frequently (71.0%), followed by P. malariae (43.2%), in all localities. The results suggest that a parasite density-dependent regulation model (with fever playing a central role) was appropriate for modelling the frequency of mixed species infections in this population. This study highlights the under-reporting of Plasmodium spp. mixed infections in the malaria-endemic area of the Colombian Amazon region and the association between causative and environmental factors in such areas.

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On the evolution and function of Plasmodium vivax reticulocyte binding surface antigen (pvrbsa)
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Camargo Ayala, P.A | 2018

The RBSA protein is encoded by a gene described in Plasmodium species having tropism for reticulocytes. Since this protein is antigenic in natural infections and can bind to target cells, it has been proposed as a potential candidate for an anti-Plasmodium vivax vaccine. However, genetic diversity (a challenge which must be overcome for ensuring fully effective vaccine design) has not been described at this locus. Likewise, the minimum regions mediating specific parasite-host interaction have not been determined. This is why the rbsa gene's evolutionary history is being here described, as well as the P. vivax rbsa (pvrbsa) genetic diversity and the specific regions mediating parasite adhesion to reticulocytes. Unlike what has previously been reported, rbsa was also present in several parasite species belonging to the monkey-malaria clade; paralogs were also found in Plasmodium parasites invading reticulocytes. The pvrbsa locus had less diversity than other merozoite surface proteins where natural selection and recombination were the main evolutionary forces involved in causing the observed polymorphism. The N-terminal end (PvRBSA-A) was conserved and under functional constraint; consequently, it was expressed as recombinant protein for binding assays. This protein fragment bound to reticulocytes whilst the C-terminus, included in recombinant PvRBSA-B (which was not under functional constraint), did not. Interestingly, two PvRBSA-A-derived peptides were able to inhibit protein binding to reticulocytes. Specific conserved and functionally important peptides within PvRBSA-A could thus be considered when designing a fully-effective vaccine against P. vivax.

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Plasmodium falciparum pre-erythrocytic stage vaccine development
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Molina Franky, Jessica | 2020

Worldwide strategies between 2010 and 2017 aimed at controlling malarial parasites (mainly Plasmodium falciparum) led to a reduction of just 18% regarding disease incidence rates. Many biologically-derived anti-malarial vaccine candidates have been developed to date; this has involved using many experimental animals, an immense amount of work and the investment of millions of dollars. This review provides an overview of the current state and the main results of clinical trials for sporozoite-targeting vaccines (i.e. the parasite stage infecting the liver) carried out by research groups in areas having variable malaria transmission rates. However, none has led to promising results regarding the effective control of the disease, thereby making it necessary to complement such efforts at finding/introducing new vaccine candidates by adopting a multi-epitope, multi-stage approach, based on minimal subunits of the main sporozoite proteins involved in the invasion of the liver.

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Plasmodium vivax in vitro continuous culture: The spoke in the wheel
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Bermúdez, Maritza | 2018

Understanding the life cycle of Plasmodium vivax is fundamental for developing strategies aimed at controlling and eliminating this parasitic species. Although advances in omic sciences and high-throughput techniques in recent years have enabled the identification and characterization of proteins which might be participating in P. vivax invasion of target cells, exclusive parasite tropism for invading reticulocytes has become the main obstacle in maintaining a continuous culture for this species. Such advance that would help in defining each parasite protein's function in the complex process of P. vivax invasion, in addition to evaluating new therapeutic agents, is still a dream. Advances related to maintenance, culture medium supplements and the use of different sources of reticulocytes and parasites (strains and isolates) have been made regarding the development of an in vitro culture for P. vivax; however, only some cultures having few replication cycles have been obtained to date, meaning that this parasite's maintenance goes beyond the technical components involved. Although it is still not yet clear which molecular mechanisms P. vivax prefers for invading young CD71+ reticulocytes [early maturation stages (I-II-III)], changes related to membrane proteins remodelling of such cells could form part of the explanation. The most relevant aspects regarding P. vivax in vitro culture and host cell characteristics have been analysed in this review to explain possible reasons why the species' continuous in vitro culture is so difficult to standardize. Some alternatives for P. vivax in vitro culture have also been described.

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Plasmodium vivax Pv12 B-cell epitopes and HLA-DRβ1-dependent T-cell epitopes in vitro antigenicity
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Yepes Pérez, Yoelis | 2018

Malaria is an infectious disease caused by parasites from the genus Plasmodium (P. falciparum and P. vivax are responsible for 90% of all clinical cases); it is widely distributed throughout the world’s tropical and subtropical regions. The P. vivax Pv12 protein is involved in invasion, is expressed on merozoite surface and has been recognised by antibodies from individuals exposed to the disease. In this study, B- and T-cell epitopes from Pv12 were predicted and characterised to advance in the design of a peptide-based vaccine against malaria. For evaluating the humoral response of individuals exposed to natural P. vivax infection from two endemic areas in Colombia, BepiPred-1.0 software was used for selecting B-cell epitopes. B-cell epitope 39038 displayed the greatest recognition by naturally-acquired antibodies and induced an IgG2/IgG4 response. NetMHCIIpan-3.1 prediction software was used for selecting peptides having high affinity binding for HLA-DRβ1* allele lineages and this was confirmed by in-vitro binding assays. T-epitopes 39113 and 39117 triggered a memory T-cell response (Stimulation Index2) and significant cytokine production. Combining in-silico, in-vitro and functional assays, two Pv12 protein regions (containing peptides 39038, 39040, 39113 and 39117) have thus been characterised as promising vaccine candidates against P. vivax malaria.

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Preliminary Evaluation of the Safety and Immunogenicity of an Antimalarial Vaccine Candidate Modified Peptide (IMPIPS) Mixture in a Murine Model
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Lambraño, Jennifer | 2019

Malaria continues being a high-impact disease regarding public health worldwide; the WHO report for malaria in 2018 estimated that 219 million cases occurred in 2017, mostly caused by the parasite Plasmodium falciparum. The disease cost the lives of more than 400,000 people, mainly in Africa. In spite of great efforts aimed at developing better prevention (i.e., a highly effective vaccine), diagnosis, and treatment methods for malaria, no efficient solution to this disease has been advanced to date. The Fundación Instituto de Inmunología de Colombia (FIDIC) has been developing studies aimed at furthering the search for vaccine candidates for controlling P. falciparum malaria. However, vaccine development involves safety and immunogenicity studies regarding their formulation in animal models before proceeding to clinical studies. The present work has thus been aimed at evaluating the safety and immunogenicity of a mixture of 23 chemically synthesised, modified peptides (immune protection-inducing protein structure (IMPIPS)) derived from different P. falciparum proteins. Single and repeat dose assays were thus used with male and female BALB/c mice which were immunised with the IMPIPS mixture. It was found that single and repeat dose immunisation with the IMPIPS mixture was safe, both locally and systemically. It was observed that the antibodies so stimulated recognised the parasite's native proteins and inhibited merozoite invasion of red blood cells in vitro when evaluating the humoral immune response induced by the IMPIPS mixture. Such results suggested that the IMPIPS peptide mixture could be a safe candidate to be tested during the next stage involved in developing an antimalarial vaccine, evaluating local safety, immunogenicity, and protection in a nonhuman primate model.

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Self-assembling functional programmable protein array for studying protein-protein interactions in malaria parasites
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Arévalo Pinzón, Gabriela | 2018

Background: Plasmodium vivax is the most widespread malarial species, causing significant morbidity worldwide. Knowledge is limited regarding the molecular mechanism of invasion due to the lack of a continuous in vitro culture system for these species. Since protein-protein and host-cell interactions play an essential role in the microorganism’s invasion and replication, elucidating protein function during invasion is critical when developing more effective control methods. Nucleic acid programmable protein array (NAPPA) has thus become a suitable technology for studying protein-protein and host-protein interactions since producing proteins through the in vitro transcription/translation (IVTT) method overcomes most of the drawbacks encountered to date, such as heterologous protein production, stability and purification. Results: Twenty P. vivax proteins on merozoite surface or in secretory organelles were selected and successfully cloned using gateway technology. Most constructs were displayed in the array expressed in situ, using the IVTT method. The Pv12 protein was used as bait for evaluating array functionality and co-expressed with P. vivax cDNA display in the array. It was found that Pv12 interacted with Pv41 (as previously described), as well as PvMSP142kDa, PvRBP1a, PvMSP8 and PvRAP1. Conclusions: NAPPA is a high-performance technique enabling co-expression of bait and query in situ, thereby enabling interactions to be analysed rapidly and reproducibly. It offers a fresh alternative for studying protein-protein and ligand-receptor interactions regarding a parasite which is difficult to cultivate (i.e. P. vivax).

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Sexual forms obtained in a continuous in vitro cultured Colombian strain of Plasmodium falciparum (FCB2)
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Ararat Sarria, Monica | 2020

Background: The epidemiological control of malaria has been hampered by the appearance of parasite resistance to anti-malarial drugs and by the resistance of mosquito vectors to control measures. This has also been associated with weak transmission control, mostly due to poor control of asymptomatic patients associated with host-vector transmission. This highlights the importance of studying the parasite's sexual forms (gametocytes) which are involved in this phase of the parasite's life-cycle. Some African and Asian strains of Plasmodium falciparum have been fully characterized regarding sexual forms' production; however, few Latin-American strains have been so characterized. This study was aimed at characterizing the Colombian FCB2 strain as a gametocyte producer able to infect mosquitoes. Methods: Gametocyte production was induced in in vitro cultured P. falciparum FCB2 and 3D7 strains. Pfap2g and Pfs25 gene expression was detected in FCB2 strain gametocyte culture by RT-PCR. Comparative analysis of gametocytes obtained from both strains was made (counts and morphological changes). In vitro zygote formation from FCB2 gametocytes was induced by incubating a gametocyte culture sample at 27 °C for 20 min. A controlled Anopheles albimanus infection was made using an artificial feed system with cultured FCB2 gametocytes (14-15 days old). Mosquito midgut dissection was then carried out for analyzing oocysts. Results: The FCB2 strain expressed Pfap2g, Pfs16, Pfg27/25 and Pfs25 sexual differentiation-related genes after in vitro sexual differentiation induction, producing gametocytes that conserved the expected morphological features. The amount of FCB2 gametocytes produced was similar to that from the 3D7 strain. FCB2 gametocytes were differentiated into zygotes and ookinetes after an in vitro low-temperature stimulus and infected An. albimanus mosquitoes, developing to oocyst stage. Conclusions: Even with the history of long-term FCB2 strain in vitro culture maintenance, it has retained its sexual differentiation ability. The gametocytes produced here preserved these parasite forms' usual characteristics and An. albimanus infection capability, thus enabling its use as a tool for studying sexual form biology, An. albimanus infection comparative analysis and anti-malarial drug and vaccine development.

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Structural analysis of owl monkey MHC-DR shows that fully-protective malaria vaccine components can be readily used in humans
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Suárez, Carlos F. | 2017

More than 50 years ago the owl monkey (genusAotus) was found to be highly susceptible to developinghuman malaria, making it an excellent experimental model for this disease. Microbes and parasites'(especially malaria) tremendous genetic variability became resolved during our malaria vaccine devel-opment, involving conserved peptides having high host cell binding activity (cHABPs); however, cHABPsare immunologically silent and must be specially modified (mHABPs) to induce a perfectfit into majorhistocompatibility complex (MHC) molecules (HLA in humans). Since malarial immunity is mainlyantibody-mediated and controlled by the HLA-DRB genetic region, ~1000Aotushave been molecularlycharacterised for MHC-DRB, revealing striking similarity between human andAotusMHC-DRB reper-tories. Such convergence suggested that a large group of immune protection-inducing protein structures(IMPIPS), highly immunogenic and protection inducers against malarial intravenous challenge inAotus,could easily be used in humans for inducing full protection against malaria. We highlight the value of alogical and rational methodology for developing a vaccine in an appropriate animal model:Aotusmonkeys

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TCR-contacting residues orientation and HLA-DRβ* binding preference determine long-lasting protective immunity against malaria
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Alba, Martha P. | 2016

Fully-protective, long-lasting, immunological (FPLLI) memory against Plasmodium falciparum malaria regarding immune protection-inducing protein structures (IMPIPS) vaccinated into monkeys previously challenged and re-challenged 60 days later with a lethal Aotus monkey-adapted P. falciparum strain was found to be associated with preferential high binding capacity to HLA-DRβ1* allelic molecules of the major histocompatibility class II (MHC-II), rather than HLA-DRβ3*, β4*, β5* alleles. Complete PPIIL 3D structure, a longer distance (26.5 Å ± 1.5 Å) between residues perfectly fitting into HLA-DRβ1*PBR pockets 1 and 9, a gauche− rotamer orientation in p8 TCR-contacting polar residue and a larger volume of polar p2 residues was also found. This data, in association with previously-described p3 and p7 apolar residues having gauche+ orientation to form a perfect MHC-II-peptide-TCR complex, determines the stereo-electronic and topochemical characteristics associated with FPLLI immunological memory.

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The in vitro antigenicity of Plasmodium vivax rhoptry neck protein 2 (PvRON2) B- and T-epitopes selected by HLA-DRB1 binding profile
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López, Carolina | 2018

Malaria caused by Plasmodium vivax is a neglected disease which is responsible for the highest morbidity in both Americas and Asia. Despite continuous public health efforts to prevent malarial infection, an effective antimalarial vaccine is still urgently needed. P. vivax vaccine development involves analyzing naturally-infected patients' immune response to the specific proteins involved in red blood cell invasion. The P. vivax rhoptry neck protein 2 (PvRON2) is a highly conserved protein which is expressed in late schizont rhoptries; it interacts directly with AMA-1 and might be involved in moving-junction formation. Bioinformatics approaches were used here to select B- and T-cell epitopes. Eleven high-affinity binding peptides were selected using the NetMHCIIpan-3.0 in silico prediction tool; their in vitro binding to HLA-DRB1*0401, HLA-DRB1*0701, HLA-DRB1*1101 or HLA-DRB1*1302 was experimentally assessed. Four peptides (39152 (HLA-DRB1*04 and 11), 39047 (HLA-DRB1*07), 39154 (HLADRB1*13) and universal peptide 39153) evoked a naturally-acquired T-cell immune response in P. vivax-exposed individuals from two endemic areas in Colombia. All four peptides had an SI greater than 2 in proliferation assays; however, only peptides 39154 and 39153 had significant differences compared to the control group. Peptide 39047 was able to significantly stimulate TNF and IL-10 production while 39154 stimulated TNF production. Allele-specific peptides (but not the universal one) were able to stimulate IL-6 production; however, none induced IFN-γ production. The Bepipred 1.0 tool was used for selecting four B-cell epitopes in silico regarding humoral response. Peptide 39041 was the only one recognized by P. vivax-exposed individuals' sera and had significant differences concerning IgG subclasses; an IgG2 > IgG4 profile was observed for this peptide, agreeing with a protection-inducing role against P. falciparum and P. vivax as previously described for antigens such as RESA and MSP2. The bioinformatics results and in vitro evaluation reported here highlighted two T-cell epitopes (39047 and 39154) being recognized by memory cells and a B-cell epitope (39041) identified by P. vivax-exposed individuals' sera which could be used as potential candidates when designing a subunit-based vaccine.

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The role of pi-interactions and hydrogen bonds in fully protective synthetic malaria vaccine development
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Reyes, César | 2017

Analysis of ourPlasmodium falciparummalaria parasite peptides'1H-NMR database in the search for H-bonds andp-interactions led us to correlate their presence or absence with a peptide's particularimmunological behavior. It was concluded that a 26.5±1.5 Å between positions 1 to 9 of the HLA-DRb1*interacting region was necessary for proper docking of 20mer-long peptides and these MHC Class IImolecules for full-protective immunity. Presence of intramolecular H-bonds orp-interactions leading torigh-handeda-helix orb-turn conformation in this peptide's region induces different immune responsesor none. PPIILconformation and the absence of any intramolecular interaction thus became thefirstfeature characterising our immune protection-inducing structures as malaria vaccine candidates

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What Is Known about the Immune Response Induced by Plasmodium vivax Malaria Vaccine Candidates?
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López, Carolina | 2017

Malaria caused by Plasmodium vivax continues being one of the most important infectious diseases around the world; P. vivax is the second most prevalent species and has the greatest geographic distribution. Developing an effective antimalarial vaccine is considered a relevant control strategy in the search for means of preventing the disease. Studying parasite-expressed proteins, which are essential in host cell invasion, has led to identifying the regions recognized by individuals who are naturally exposed to infection. Furthermore, immunogenicity studies have revealed that such regions can trigger a robust immune response that can inhibit sporozoite (hepatic stage) or merozoite (erythrocyte stage) invasion of a host cell and induce protection. This review provides a synthesis of the most important studies to date concerning the antigenicity and immunogenicity of both synthetic peptide and recombinant protein candidates for a vaccine against malaria produced by P. vivax.

LEER

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Browsing by Subject "Plasmodium falciparum"

Behavior and abundance of Anopheles darlingi in communities living in the Colombian Amazon riverside ﻿

Conserved binding regions provide the clue for peptide-based vaccine development: A chemical perspective ﻿

Easy and fast method for expression and native extraction of Plasmodium vivax Duffy binding protein fragments ﻿

Malaria: Paving the way to developing peptide-based vaccines against invasion in infectious diseases ﻿

Micro-epidemiology of mixed-species malaria infections in a rural population living in the Colombian Amazon region ﻿

On the evolution and function of Plasmodium vivax reticulocyte binding surface antigen (pvrbsa) ﻿

Plasmodium falciparum pre-erythrocytic stage vaccine development ﻿

Plasmodium vivax in vitro continuous culture: The spoke in the wheel ﻿

Plasmodium vivax Pv12 B-cell epitopes and HLA-DRβ1-dependent T-cell epitopes in vitro antigenicity ﻿

Preliminary Evaluation of the Safety and Immunogenicity of an Antimalarial Vaccine Candidate Modified Peptide (IMPIPS) Mixture in a Murine Model ﻿

Self-assembling functional programmable protein array for studying protein-protein interactions in malaria parasites ﻿

Sexual forms obtained in a continuous in vitro cultured Colombian strain of Plasmodium falciparum (FCB2) ﻿

Structural analysis of owl monkey MHC-DR shows that fully-protective malaria vaccine components can be readily used in humans ﻿

TCR-contacting residues orientation and HLA-DRβ* binding preference determine long-lasting protective immunity against malaria ﻿

The in vitro antigenicity of Plasmodium vivax rhoptry neck protein 2 (PvRON2) B- and T-epitopes selected by HLA-DRB1 binding profile ﻿

The role of pi-interactions and hydrogen bonds in fully protective synthetic malaria vaccine development ﻿

What Is Known about the Immune Response Induced by Plasmodium vivax Malaria Vaccine Candidates? ﻿

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Behavior and abundance of Anopheles darlingi in communities living in the Colombian Amazon riverside

Conserved binding regions provide the clue for peptide-based vaccine development: A chemical perspective

Easy and fast method for expression and native extraction of Plasmodium vivax Duffy binding protein fragments

Malaria: Paving the way to developing peptide-based vaccines against invasion in infectious diseases

Micro-epidemiology of mixed-species malaria infections in a rural population living in the Colombian Amazon region

On the evolution and function of Plasmodium vivax reticulocyte binding surface antigen (pvrbsa)

Plasmodium falciparum pre-erythrocytic stage vaccine development

Plasmodium vivax in vitro continuous culture: The spoke in the wheel

Plasmodium vivax Pv12 B-cell epitopes and HLA-DRβ1-dependent T-cell epitopes in vitro antigenicity

Preliminary Evaluation of the Safety and Immunogenicity of an Antimalarial Vaccine Candidate Modified Peptide (IMPIPS) Mixture in a Murine Model

Self-assembling functional programmable protein array for studying protein-protein interactions in malaria parasites

Sexual forms obtained in a continuous in vitro cultured Colombian strain of Plasmodium falciparum (FCB2)

Structural analysis of owl monkey MHC-DR shows that fully-protective malaria vaccine components can be readily used in humans

TCR-contacting residues orientation and HLA-DRβ* binding preference determine long-lasting protective immunity against malaria

The in vitro antigenicity of Plasmodium vivax rhoptry neck protein 2 (PvRON2) B- and T-epitopes selected by HLA-DRB1 binding profile

The role of pi-interactions and hydrogen bonds in fully protective synthetic malaria vaccine development

What Is Known about the Immune Response Induced by Plasmodium vivax Malaria Vaccine Candidates?

Behavior and abundance of Anopheles darlingi in communities living in the Colombian Amazon riverside

Conserved binding regions provide the clue for peptide-based vaccine development: A chemical perspective

Easy and fast method for expression and native extraction of Plasmodium vivax Duffy binding protein fragments

Malaria: Paving the way to developing peptide-based vaccines against invasion in infectious diseases

Micro-epidemiology of mixed-species malaria infections in a rural population living in the Colombian Amazon region

On the evolution and function of Plasmodium vivax reticulocyte binding surface antigen (pvrbsa)

Plasmodium falciparum pre-erythrocytic stage vaccine development

Plasmodium vivax in vitro continuous culture: The spoke in the wheel

Plasmodium vivax Pv12 B-cell epitopes and HLA-DRβ1-dependent T-cell epitopes in vitro antigenicity

Preliminary Evaluation of the Safety and Immunogenicity of an Antimalarial Vaccine Candidate Modified Peptide (IMPIPS) Mixture in a Murine Model

Self-assembling functional programmable protein array for studying protein-protein interactions in malaria parasites

Sexual forms obtained in a continuous in vitro cultured Colombian strain of Plasmodium falciparum (FCB2)

Structural analysis of owl monkey MHC-DR shows that fully-protective malaria vaccine components can be readily used in humans

TCR-contacting residues orientation and HLA-DRβ* binding preference determine long-lasting protective immunity against malaria

The in vitro antigenicity of Plasmodium vivax rhoptry neck protein 2 (PvRON2) B- and T-epitopes selected by HLA-DRB1 binding profile

The role of pi-interactions and hydrogen bonds in fully protective synthetic malaria vaccine development

What Is Known about the Immune Response Induced by Plasmodium vivax Malaria Vaccine Candidates?