Asexual blood-stage malaria vaccine development: facing the challenges

2007 ◽  
Vol 20 (5) ◽  
pp. 467-475 ◽  
Author(s):  
Blaise Genton ◽  
Zarifah H Reed
Keyword(s):  
Malaria Vaccine ◽  
Vaccine Development ◽  
Blood Stage ◽  
Asexual Blood Stage ◽  
Blood Stage Malaria

Gold(i) phosphine compounds as parasite attenuating agents for malaria vaccine and drug development

Metallomics ◽  
2018 ◽  
Vol 10 (3) ◽  
pp. 444-454 ◽  
Author(s):  
Aloysious Ssemaganda ◽  
Leanne M. Low ◽  
Krista R. Verhoeft ◽  
Mathias Wambuzi ◽  
Barbarah Kawoozo ◽  
...  
Keyword(s):  
Drug Development ◽  
Malaria Vaccine ◽  
Vaccine Development ◽  
Blood Stage ◽  
Asexual Blood Stage ◽  
Novel Strategy

The asexual blood-stagePlasmodiumparasite attenuating properties of gold(i) phosphine compounds are exploited in a novel strategy for malaria vaccine development.

scholarly journals Identification of a Potent Combination of Key Plasmodium falciparum Merozoite Antigens That Elicit Strain-Transcending Parasite-Neutralizing Antibodies

2012 ◽  
Vol 81 (2) ◽  
pp. 441-451 ◽  
Author(s):  
Alok K. Pandey ◽  
K. Sony Reddy ◽  
Tajali Sahar ◽  
Sonal Gupta ◽  
Hina Singh ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Neutralizing Antibodies ◽  
Malaria Vaccine ◽  
Vaccine Development ◽  
Blood Stage ◽  
Content Type ◽  
Receptor Blocking ◽  
Erythrocyte Invasion ◽  
Invasion Inhibition ◽  
Blood Stage Malaria

ABSTRACTBlood-stage malaria vaccines that target singlePlasmodium falciparumantigens involved in erythrocyte invasion have not induced optimal protection in field trials. Blood-stage malaria vaccine development has faced two major hurdles, antigenic polymorphisms and molecular redundancy, which have led to an inability to demonstrate potent, strain-transcending, invasion-inhibitory antibodies. Vaccines that target multiple invasion-related parasite proteins may inhibit erythrocyte invasion more efficiently. Our approach is to develop a receptor-blocking blood-stage vaccine againstP. falciparumthat targets the erythrocyte binding domains of multiple parasite adhesins, blocking their interaction with their receptors and thus inhibiting erythrocyte invasion. However, with numerous invasion ligands, the challenge is to identify combinations that elicit potent strain-transcending invasion inhibition. We evaluated the invasion-inhibitory activities of 20 different triple combinations of antibodies mixedin vitroagainst a diverse set of six key merozoite ligands, including the novel ligandsP. falciparumapical asparagine-rich protein (PfAARP), EBA-175 (PfF2),P. falciparumreticulocyte binding-like homologous protein 1 (PfRH1), PfRH2, PfRH4, andPlasmodiumthrombospondin apical merozoite protein (PTRAMP), which are localized in different apical organelles and are translocated to the merozoite surface at different time points during invasion. They bind erythrocytes with different specificities and are thus involved in distinct invasion pathways. The antibody combination of EBA-175 (PfF2), PfRH2, and PfAARP produced the most efficacious strain-transcending inhibition of erythrocyte invasion against diverseP. falciparumclones. This potent antigen combination was selected for coimmunization as a mixture that induced balanced antibody responses against each antigen and inhibited erythrocyte invasion efficiently. We have thus demonstrated a novel two-step screening approach to identify a potent antigen combination that elicits strong strain-transcending invasion inhibition, supporting its development as a receptor-blocking malaria vaccine.

scholarly journals Development of an asexual blood stage malaria vaccine

Blood ◽  
1989 ◽  
Vol 74 (2) ◽  
pp. 537-546 ◽  
Author(s):  
A Moreno ◽  
ME Patarroyo
Keyword(s):  
Malaria Vaccine ◽  
Blood Stage ◽  
Asexual Blood Stage ◽  
Blood Stage Malaria

scholarly journals Controlled Human Malaria Infection of Healthy Adults With Lifelong Malaria Exposure to Assess Safety, Immunogenicity, and Efficacy of the Asexual Blood Stage Malaria Vaccine Candidate GMZ2

2018 ◽  
Vol 69 (8) ◽  
pp. 1377-1384 ◽  
Author(s):  
Jean Claude Dejon-Agobe ◽  
Ulysse Ateba-Ngoa ◽  
Albert Lalremruata ◽  
Andreas Homoet ◽  
Julie Engelhorn ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Specific Antibody ◽  
Malaria Infection ◽  
Malaria Vaccine ◽  
Blood Stage ◽  
Control Group ◽  
Asexual Blood Stage ◽  
Human Malaria ◽  
Controlled Human Malaria Infection ◽  
Blood Stage Malaria

AbstractBackgroundGMZ2 is a recombinant malaria vaccine inducing immune responses against Plasmodium falciparum (Pf) merozoite surface protein-3 and glutamate-rich protein. We used standardized controlled human malaria infection (CHMI) to assess the efficacy of this asexual blood-stage vaccine.MethodsWe vaccinated 50 healthy, adult volunteers with lifelong exposure to Pf 3 times, at 4-week intervals, with 30 or 100 µg GMZ2 formulated in CAF01, a liposome-based adjuvant; 100 µg GMZ2, formulated in Alhydrogel; or a control vaccine (Verorab). Approximately 13 weeks after the last vaccination, 35/50 volunteers underwent CHMI by direct venous inoculation of 3200 Pf sporozoites (Sanaria® PfSPZ Challenge).ResultsAdverse events were similarly distributed between GMZ2 and control vaccinees. Baseline-corrected anti-GMZ2 antibody concentrations 4 weeks after the last vaccination were higher in all 3 GMZ2-vaccinated arms, compared to the control group. All GMZ2 formulations induced similar antibody levels. CHMI resulted in 29/34 (85%) volunteers with Pf parasitemia and 15/34 (44%) with malaria (parasitemia and symptoms). The proportion of participants with malaria (2/5 control, 6/10 GMZ2-Alhydrogel, 2/8 30 µg GMZ2-CAF01, and 5/11 100 µg GMZ2-CAF01) and the time it took them to develop malaria were similar in all groups. Baseline, vaccine-specific antibody concentrations were associated with protection against malaria.ConclusionsGMZ2 is well tolerated and immunogenic in lifelong–Pf-exposed adults from Gabon, with similar antibody responses regardless of formulation. CHMI showed no protective effect of prior vaccination with GMZ2, although baseline, vaccine-specific antibody concentrations were associated with protection. CHMI with the PfSPZ Challenge is a potent new tool to validate asexual, blood-stage malaria vaccines in Africa.Clinical Trials RegistrationPan-African Clinical Trials: PACTR201503001038304

scholarly journals Molecular Basis of Allele-Specific Efficacy of a Blood-Stage Malaria Vaccine: Vaccine Development Implications

2012 ◽  
Vol 207 (3) ◽  
pp. 511-519 ◽  
Author(s):  
Amed Ouattara ◽  
Shannon Takala-Harrison ◽  
Mahamadou A. Thera ◽  
Drissa Coulibaly ◽  
Amadou Niangaly ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Malaria Vaccine ◽  
Vaccine Development ◽  
Blood Stage ◽  
Allele Specific ◽  
Blood Stage Malaria

scholarly journals The Blood Stage Antigen RBP2-P1 of Plasmodium vivax Binds Reticulocytes and Is a Target of Naturally Acquired Immunity

2020 ◽  
Vol 88 (4) ◽  
Author(s):  
Anongruk Chim-Ong ◽  
Thitiporn Surit ◽  
Sittinont Chainarin ◽  
Wanlapa Roobsoong ◽  
Jetsumon Sattabongkot ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Malaria Vaccine ◽  
Vaccine Development ◽  
Binding Protein ◽  
Blood Stage ◽  
Content Type ◽  
Binding Inhibition ◽  
Erythrocyte Binding ◽  
Blood Stage Malaria

ABSTRACT The interactions between Plasmodium parasites and human erythrocytes are prime targets of blood stage malaria vaccine development. The reticulocyte binding protein 2-P1 (RBP2-P1) of Plasmodium vivax, a member of the reticulocyte binding protein family, has recently been shown to be highly antigenic in several settings endemic for malaria. Yet, its functional characteristics and the relevance of its antibody response in human malaria have not been examined. In this study, the potential function of RBP2-P1 as an invasion ligand of P. vivax was evaluated. The protein was found to be expressed in schizonts, be localized at the apical end of the merozoite, and preferentially bind reticulocytes over normocytes. Human antibodies to this protein also exhibit erythrocyte binding inhibition at physiologically relevant concentrations. Furthermore, RBP2-P1 antibodies are associated with lower parasitemia and tend to be higher in asymptomatic carriers than in patients. This study provides evidence supporting a role of RBP2-P1 as an invasion ligand and its consideration as a vaccine target.

Examining cellular immune responses to inform development of a blood-stage malaria vaccine

Parasitology ◽  
2016 ◽  
Vol 143 (2) ◽  
pp. 208-223 ◽  
Author(s):  
DANIELLE I. STANISIC ◽  
MICHAEL F. GOOD
Keyword(s):  
Immune Responses ◽  
Malaria Vaccine ◽  
Vaccine Development ◽  
Clinical Symptoms ◽  
Field Studies ◽  
Blood Stage ◽  
Number Of Factors ◽  
Different Response ◽  
Cellular Immune ◽  
Blood Stage Malaria

SUMMARYNaturally acquired immunity to the blood-stage of the malaria parasite develops slowly in areas of high endemicity, but is not sterilizing. It manifests as a reduction in parasite density and clinical symptoms. Immunity as a result of blood-stage vaccination has not yet been achieved in humans, although there are many animal models where vaccination has been successful. The development of a blood-stage vaccine has been complicated by a number of factors including limited knowledge of human-parasite interactions and which antigens and immune responses are critical for protection. Opinion is divided as to whether this vaccine should aim to accelerate the acquisition of responses acquired following natural exposure, or whether it should induce a different response. Animal and experimental human models suggest that cell-mediated immune responses can control parasite growth, but these responses can also contribute to significant immunopathology if unregulated. They are largely ignored in most blood-stage malaria vaccine development strategies. Here, we discuss key observations relating to cell-mediated immune responses in the context of experimental human systems and field studies involving naturally exposed individuals and how this may inform the development of a blood-stage malaria vaccine.

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