EDCTP Alumni Network

Fostering excellence and collaboration in the next generation of researchers

Call Career Development Fellowship (CDF)
Programme EDCTP2
Start Date 2021-10-01
End Date 2024-09-30
Project Code TMA2020CDF-3203
Status Active

Title

Systematic prioritization and initial characterization of Plasmodium falciparum vaccine antigens against pregnancy associated malaria

Host Organisation

Institution Country

Current Organisation

Mount Kenya University

Publications

Authors:
Sakamoto, H.
Takeo, S.
Takashima, E.
Miura, K.
Kanoi, B.N.
Kaneko, T.
Han, E.-T.
Tachibana, M.
Matsuoka, K.
Sattabongkot, J.
Udomsangpetch, R.
Ishino, T.
Tsuboi, T.
Date:
2018-01-01
Journal:
Parasitology International
Content:
Authors:
Morita, M.
Nagaoka, H.
Ntege, E.H.
Kanoi, B.N.
Ito, D.
Nakata, T.
Lee, J.-W.
Tokunaga, K.
Iimura, T.
Torii, M.
Tsuboi, T.
Takashima, E.
Date:
2018-01-01
Journal:
Scientific Reports
Content:
Authors:
Date:
2020-04-20
Journal:
Scientific reports
Content:
Plasmodium falciparum merozoite invasion into erythrocytes is an essential step of the blood-stage cycle, survival of parasites, and malaria pathogenesis. P. falciparum merozoite Rh5 interacting protein (PfRipr) forms a complex with Rh5 and CyRPA in sequential molecular events leading to erythrocyte invasion. Recently we described PfRipr as a conserved protein that induces strain-transcending growth inhibitory antibodies in in vitro assays. However, being a large and complex protein of 1086 amino acids (aa) with 87 cysteine residues, PfRipr is difficult to express in conventional expression systems towards vaccine development. In this study we sought to identify the most potent region of PfRipr that could be developed to overcome difficulties related to protein expression, as well as to elucidate the invasion inhibitory mechanism of anti-PfRipr antibodies. Using the wheat germ cell-free system, Ecto- PfRipr and truncates of approximately 200 aa were expressed as soluble proteins. We demonstrate that antibodies against PfRipr truncate 5 (PfRipr_5: C720-D934), a region within the PfRipr C-terminal EGF-like domains, potently inhibit merozoite invasion. Furthermore, the antibodies strongly block PfRipr/Rh5 interaction, as well as that between PfRipr and its erythrocyte-surface receptor, SEMA7A. Taken together, PfRipr_5 is a potential candidate for further development as a blood-stage malaria vaccine.
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This article originally appeared in HIV & AIDS treatment in practice, an email newsletter for healthcare workers and community-based organisations in resource-limited settings published by NAM between 2003 and 2014.
Identifiers:
Authors:
Kanoi BN , author
Egwang TG , author
Date:
2021-05-01
Journal:
Parasitology international
Content:
Identifiers:
Authors:
Proietti, C.
Verra, F.
Bretscher, M.T.
Stone, W.
Kanoi, B.N.
Balikagala, B.
Egwang, T.G.
Corran, P.
Ronca, R.
Arcà, B.
Riley, E.M.
Crisanti, A.
Drakeley, C.
Bousema, T.
Date:
2013-01-01
Journal:
Parasite Immunology
Content:
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Authors:
Date:
2020-05-12
Journal:
Frontiers in immunology
Content:
Clinical immunity to malaria develops after repeated exposure to Plasmodium falciparum parasites. Broadly reactive antibodies against parasite antigens expressed on the surface of infected erythrocytes (variable surface antigens; VSAs) are candidates for anti-malaria therapeutics and vaccines. Among the VSAs, several RIFIN, STEVOR, and SURFIN family members have been demonstrated to be targets of naturally acquired immunity against malaria. For example, RIFIN family members are important ligands for opsonization of P. falciparum infected erythrocytes with specific immunoglobulins (IgG) acquiring broad protective reactivity. However, the global repertoire of human anti-VSAs IgG, its variation in children, and the key protective targets remain poorly understood. Here, we report wheat germ cell-free system-based production and serological profiling of a comprehensive library of A-RIFINs, B-RIFINs, STEVORs, and SURFINs derived from the P. falciparum 3D7 parasite strain. We observed that >98% of assayed proteins (n = 265) were immunogenic in malaria-exposed individuals in Uganda. The overall breadth of immune responses was significantly correlated with age but not with clinical malaria outcome among the study volunteers. However, children with high levels of antibodies to four RIFINs (PF3D7_0201000, PF3D7_1254500, PF3D7_1040600, PF3D7_1041100), STEVOR (PF3D7_0732000), and SURFIN 1.2 (PF3D7_0113600) had prospectively reduced the risk of developing febrile malaria, suggesting that the 5 antigens are important targets of protective immunity. Further studies on the significance of repeated exposure to malaria infection and maintenance of such high-level antibodies would contribute to a better understanding of susceptibility and naturally acquired immunity to malaria.
Identifiers:
Authors:
Proietti, C.
Pettinato, D.D.
Kanoi, B.N.
Ntege, E.
Crisanti, A.
Riley, E.M.
Egwang, T.G.
Drakeley, C.
Bousema, T.
Date:
2011-01-01
Journal:
American Journal of Tropical Medicine and Hygiene
Content:
Authors:
Palacpac, N.M.Q.
Ntege, E.
Balikagala, B.
Yeka, A.
Shirai, H.
Suzuki, N.
Nsereko, C.
Kanoi, B.N.
Okada, T.
Egwang, T.G.
Horii, T.
Date:
2014-01-01
Journal:
International Journal of Environmental Research and Public Health
Content:
Authors:
Palacpac, N.M.Q.
Ntege, E.
Yeka, A.
Balikagala, B.
Suzuki, N.
Shirai, H.
Yagi, M.
Ito, K.
Fukushima, W.
Hirota, Y.
Nsereko, C.
Okada, T.
Kanoi, B.N.
Tetsutani, K.
Arisue, N.
Itagaki, S.
Tougan, T.
Ishii, K.J.
Ueda, S.
Egwang, T.G.
Horii, T.
Date:
2013-01-01
Journal:
PLoS ONE
Content:
Authors:
Kanoi, B.N.
Nagaoka, H.
Morita, M.
White, M.T.
Palacpac, N.M.Q.
Ntege, E.H.
Balikagala, B.
Yeka, A.
Egwang, T.G.
Horii, T.
Tsuboi, T.
Takashima, E.
Date:
2018-01-01
Journal:
Vaccine
Content:
Authors:
Date:
2019-04-11
Journal:
Scientific reports
Content:
Malaria symptoms and pathology are initiated by invasion of host erythrocytes by Plasmodium merozoites in a complex process that involves interactions between parasite and host erythrocyte proteins. Erythrocyte invasion presents attractive targets for malaria vaccine and drug development. Recently it was observed that antibodies against PfMSA180 (PF3D7_1014100) are associated with protection from symptomatic malaria, suggesting that this protein is a target of naturally acquired protective antibodies. Here we characterize PfMSA180, a ~170 kDa merozoite surface antigen that is potentially involved in erythrocyte invasion. PfMSA180 synthesized by the wheat germ cell-free system was used to raise antibodies in rabbits. Growth inhibition assays revealed that parasite invasion is inhibited by antibodies to the PfMSA180 C-terminal region, which contains an erythrocyte-binding domain. Surface plasmon resonance analysis showed that PfMSA180 specifically interacts with human erythrocyte integrin associated protein (CD47), suggesting that PfMSA180 plays a role during merozoite invasion of erythrocytes. Polymorphism analysis revealed that pfmsa180 is highly conserved among field isolates. We show that naturally acquired PfMSA180-specific antibodies responses are associated with protective immunity in a malaria-exposed Thai population. In sum, the data presented here supports further evaluation of the conserved erythrocyte-binding C-terminal region of PfMSA180 as an asexual blood-stage malaria vaccine candidate.
Identifiers:
Authors:
Kanoi, B.N.
Takashima, E.
Morita, M.
White, M.T.
Palacpac, N.M.Q.
Ntege, E.H.
Balikagala, B.
Yeka, A.
Egwang, T.G.
Horii, T.
Tsuboi, T.
Date:
2017-01-01
Journal:
Vaccine
Content:
Authors:
Palacpac NM , author
Yagi M , author
Ntege E , author
Balikagala B , author
Yeka A , author
Shirai H , author
Suzuki N , author
Okada T , author
Kanoi B , author
Nobuko A , author
Tougan T , author
Ishii KJ , author
Egwang TG , author
Horii T , author
Date:
2014-09-01
Journal:
Malaria journal
Content:
Identifiers:
PMC: PMC4179423
Authors:
Date:
2020-10-30
Journal:
Parasitology international
Content:
Vaccines against infectious diseases have had great successes in the history of public health. Major breakthroughs have occurred in the development of vaccine-based interventions against viral and bacterial pathogens through the application of classical vaccine design strategies. In contrast the development of a malaria vaccine has been slow. Plasmodium falciparum malaria affects millions of people with nearly half of the world population at risk of infection. Decades of dedicated research has taught us that developing an effective vaccine will be time consuming, challenging, and expensive. Nevertheless, recent advancements such as the optimization of robust protein synthesis platforms, high-throughput immunoscreening approaches, reverse vaccinology, structural design of immunogens, lymphocyte repertoire sequencing, and the utilization of artificial intelligence, have renewed the prospects of an accelerated discovery of the key antigens in malaria. A deeper understanding of the major factors underlying the immunological and molecular mechanisms of malaria might provide a comprehensive approach to identifying novel and highly efficacious vaccines. In this review we discuss progress in novel antigen discoveries that leverage on the wheat germ cell-free protein synthesis system (WGCFS) to accelerate malaria vaccine development.
Identifiers:
Authors:
Yuguchi T , author
Kanoi BN , author
Nagaoka H , author
Miura T , author
Ito D , author
Takeda H , author
Tsuboi T , author
Takashima E , author
Otsuki H , author
Date:
2021-04-01
Journal:
Frontiers in cellular and infection microbiology
Content:
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Authors:
Date:
2017-09-11
Journal:
PLoS neglected tropical diseases
Content:
Plasmodium vivax remains an important cause of malaria in South America and the Asia-Pacific. Naturally acquired antibody responses against multiple P. vivax proteins have been described in numerous countries, however, direct comparison of these responses has been difficult with different methodologies employed. We measured antibody responses against 307 P. vivax proteins at the time of P. vivax infection, and at 2-3 later time-points in three countries. We observed that seropositivity rates at the time of infection were highest in Thailand, followed by Brazil then PNG, reflecting the level of antigenic input. The majority of sero-reactive antigens in all sites induced short-lived antibody responses with estimated half-lives of less than 6 months, although there was a trend towards longer-lived responses in PNG children. Despite these differences, IgG seropositivity rates, magnitude and longevity were highly and significantly rank-correlated between the different regions, suggesting such features are reflective of the individual protein.
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Date:
2019-10-03
Journal:
Expert Review of Vaccines
Content:
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DOI: 10.1080/14760584.2019.1674145
Part of ISSN: 1476-0584
Part of ISSN: 1744-8395
Authors:
Date:
2019-04-06
Journal:
Transactions of the Royal Society of Tropical Medicine and Hygiene
Content:
BACKGROUND:Plasmodium ovale and Plasmodium malariae infections are scarcely studied in sub-Saharan Africa, where the Plasmodium falciparum species predominates. The objective of this study is to investigate the prevalence of P. ovale and P. malariae infections and their relationship with common red blood cell polymorphisms in a cohort of 509 individuals from Uganda. METHODS:Three cross-sectional surveys were conducted in individuals of 1-10 and >20 y of age from the Apac district at baseline and 6 and 16 weeks after drug treatment. Malaria infections were assessed by polymerase chain reaction and genotyping was performed for the sickle-cell allele, α-thalassaemia and glucose-6-phosphate dehydrogenase. RESULTS:At baseline, the prevalence of infection was 7.5%, 12.6% and 57.4% for P. ovale, P. malariae and P. falciparum species, respectively. Co-infections were present in 14.1% of individuals, all including P. falciparum parasites. In children 1-5 y of age, the prevalence of P. ovale mono-infections increased significantly from 1.7% to 7.3% over time (p=0.004) while the prevalence of P. malariae and P. falciparum infections declined significantly during this study. After adjusting for confounding and multiple testing, only α-thalassaemia had a statistically significant increase in the odds of P. falciparum infections (odds ratio 1.93 [95% confidence interval 1.26 to 2.94]). CONCLUSIONS:Common red blood cell polymorphisms do not show strong effects on mild Plasmodium infections in this Ugandan population. To understand the extent of this result, similar studies should be carried out in other populations using larger cohorts.
Identifiers:
Authors:
Yagi, M.
Palacpac, N.M.Q.
Ito, K.
Oishi, Y.
Itagaki, S.
Balikagala, B.
Ntege, E.H.
Yeka, A.
Kanoi, B.N.
Katuro, O.
Shirai, H.
Fukushima, W.
Hirota, Y.
Egwang, T.G.
Horii, T.
Date:
2016-01-01
Journal:
Scientific Reports
Content:
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Authors:
Date:
2020-11-02
Journal:
Parasitology international
Content:
During intraerythrocytic development Plasmodium falciparum deploys numerous proteins to support erythrocyte invasion, intracellular growth and development, as well as host immune evasion. Since these proteins are key for parasite intraerythrocytic survival and propagation, they represent attractive targets for antimalarial vaccines. In this study we sought to characterize a member of the PHISTc family of proteins, PF3D7_0801000, as a potential vaccine target. Using the wheat germ cell-free system we expressed the N-terminal region of PF3D7_0801000 (G93-L494, PF3D7_0801000N) and generated specific immune sera. We observed that PF3D7_0801000 localizes in merozoites, and antibodies against PF3D7_0801000N modestly inhibit P. falciparum parasite growth in in vitro culture. Sliding window analysis of the coding sequence revealed that pf3d7_0801000n is relatively conserved among African parasite isolates. Antibody profiles in a malaria-exposed Ugandan population revealed that PF3D7_0801000N is strongly immunoreactive with antibody acquisition increasing with age. Taken together, these findings suggest the need for further evaluation of PF3D7_0801000 for its role in merozoite invasion and utility as an asexual blood-stage vaccine candidate antigen.
Identifiers:
Authors:
Kanoi, B.N.
Egwang, T.G.
Date:
2007-01-01
Journal:
Current Opinion in Infectious Diseases
Content:

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