A5089823757- Malaria Research and Control
- Mosquito-borne diseases and control
- Complement system in diseases
- HIV Research and Treatment
- Invertebrate Immune Response Mechanisms
- vaccines and immunoinformatics approaches
- Computational Drug Discovery Methods
- Parasites and Host Interactions
- Trypanosoma species research and implications
- Research on Leishmaniasis Studies
- Hepatitis B Virus Studies
- Monoclonal and Polyclonal Antibodies Research
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- SARS-CoV-2 and COVID-19 Research
- Hepatitis C virus research
- Transgenic Plants and Applications
- Vector-borne infectious diseases
- Insect Resistance and Genetics
- Immunotherapy and Immune Responses
- Drug Transport and Resistance Mechanisms
- Viral Infections and Vectors
- Biochemical and Structural Characterization
- HIV/AIDS drug development and treatment
- Parasitic infections in humans and animals
National Institutes of Health
2016-2025
National Institute of Allergy and Infectious Diseases
2016-2025
Vector Oncology (United States)
2012-2025
Vector (United States)
2017-2024
Johns Hopkins University
2023
University of Victoria
2023
Government of the United States of America
2023
University of Kansas
2017
Kelly Services (United States)
2015
Tottori University
1998-2012
Background Pfs25 and Pvs25, surface proteins of mosquito stage the malaria parasites P. falciparum vivax, respectively, are leading candidates for vaccines preventing transmission by mosquitoes. This single blinded, dose escalating, controlled Phase 1 study assessed safety immunogenicity recombinant Pvs25 formulated with Montanide ISA 51, a water-in-oil emulsion. Methodology/Principal Findings The trial was conducted at Johns Hopkins Center Immunization Research, Washington DC, USA, between...
Antigenic diversity has posed a critical barrier to vaccine development against the pathogenic blood-stage infection of human malaria parasite Plasmodium falciparum. To date, only strain-specific protection been reported by trials such vaccines in nonhuman primates. We recently showed that P. falciparum reticulocyte binding protein homolog 5 (PfRH5), merozoite adhesin required for erythrocyte invasion, is highly susceptible vaccine-inducible strain-transcending parasite-neutralizing...
BackgroundDevelopment of an effective vaccine against the pathogenic blood-stage infection human malaria has proved challenging, and no candidate affected parasitemia following controlled (CHMI) with Plasmodium falciparum.MethodsWe undertook a phase I/IIa clinical trial in healthy adults United Kingdom RH5.1 recombinant protein vaccine, targeting P. falciparum reticulocyte-binding homolog 5 (RH5), formulated AS01B adjuvant. We assessed safety, immunogenicity, efficacy CHMI. Trial registered...
A blood-stage Plasmodium falciparum malaria vaccine would provide a second line of defence to complement partially effective or waning immunity conferred by the approved pre-erythrocytic vaccines. RH5.1 is soluble protein candidate for P falciparum, formulated with Matrix-M adjuvant assess safety and immunogenicity in malaria-endemic adult paediatric population first time.
Immunity to Plasmodium falciparum (Pf) malaria is only acquired after years of repeated infections and wanes rapidly without ongoing parasite exposure. Antibodies are central immunity, yet little known about the B-cell biology that underlies inefficient acquisition Pf-specific humoral immunity. This year-long prospective study in Mali 185 individuals aged 2 25 shows memory B-cells antibodies gradually a stepwise fashion over Pf Both B cells antibody titers increased acute then, six months...
The induction of cellular immunity, in conjunction with antibodies, may be essential for vaccines to protect against blood-stage infection the human malaria parasite Plasmodium falciparum. We have shown that prime-boost delivery P. falciparum antigens by chimpanzee adenovirus 63 (ChAd63) followed attenuated orthopoxvirus MVA is safe and immunogenic healthy adults. Here, we report on vaccine efficacy controlled delivered mosquito bites. were administered alone, or together (MSP1+AMA1), a...
Efficacy trials of antibody-inducing protein-in-adjuvant vaccines targeting the blood-stage Plasmodium falciparum malaria parasite have so far shown disappointing results. The induction cell-mediated responses in conjunction with antibody is thought to be one alternative strategy that could achieve protective efficacy humans. Here, we prepared chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) replication-deficient vectors encoding well-studied P. antigen merozoite...
Background Traditionally, vaccine development against the blood-stage of Plasmodium falciparum infection has focused on recombinant protein-adjuvant formulations in order to induce high-titer growth-inhibitory antibody responses. However, date no such encoding a antigen(s) alone induced significant protective efficacy erythrocytic-stage pre-specified primary endpoint Phase IIa/b clinical trial designed assess efficacy. Cell-mediated responses, acting conjunction with functional antibodies,...
Highlights•Human PfRH5 vaccination induces cross-reactive neutralizing antimalarial antibodies•Neutralizing human antibodies bind epitopes close to the basigin binding site•Some non-neutralizing potentiate those several malaria proteins•Potentiating slow erythrocyte invasion by a new epitope on PfRH5SummaryThe Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) is leading target for next-generation vaccines against disease-causing blood-stage of malaria. However, little...
No vaccine has yet proven effective against the blood-stages of Plasmodium falciparum, which cause symptoms and severe manifestations malaria. We recently found that PfRH5, a P. falciparum-specific protein expressed in merozoites, is efficiently targeted by broadly-neutralizing, vaccine-induced antibodies. Here we show antibodies PfRH5 inhibit vitro growth short-term-adapted parasite isolates from Cambodia, EC(50) values antigen-specific are lower than those PfAMA1. Since antibody responses...
The development of a highly effective vaccine remains key strategic goal to aid the control and eventual eradication Plasmodium falciparum malaria. In recent years, reticulocyte-binding protein homolog 5 (RH5) has emerged as most promising blood-stage P. candidate antigen date, capable conferring protection against stringent challenge in Aotus monkeys. We report on first clinical trial our knowledge assess RH5 — dose-escalation phase Ia study 24 healthy, malaria-naive adult volunteers....
Vaccines that interrupt malaria transmission are of increasing interest and a robust functional assay to measure this activity would promote their development by providing biologically relevant means evaluating potential vaccine candidates. Therefore, we aimed qualify the standard membrane-feeding (SMFA). The measures transmission-blocking antibodies feeding cultured P. falciparum gametocytes Anopheles mosquitoes in presence test measuring subsequent mosquito infection. International...
ABSTRACT Recently, there has been a renewed interest in the development of transmission-blocking vaccines (TBV) against Plasmodium falciparum malaria. While several candidate TBVs have reported, studies directly comparing them functional assays are limited. To this end, recombinant proteins TBV candidates Pfs25, Pfs230, and PfHAP2 were expressed wheat germ cell-free expression system. Outbred CD-1 mice immunized twice with antigens. Two weeks after second immunization, IgG levels measured by...
Background. Plasmodium falciparum reticulocyte-binding protein homologue 5 (PfRH5) is a blood-stage parasite essential for host erythrocyte invasion. PfRH5-specific antibodies raised in animals inhibit growth vitro, but the relevance of naturally acquired humans unclear.
Background. Models of controlled human malaria infection (CHMI) initiated by mosquito bite have been widely used to assess efficacy preerythrocytic vaccine candidates in small proof-of-concept phase 2a clinical trials. Efficacy testing blood-stage parasite vaccines, however, has generally relied on larger-scale 2b field trials malaria-endemic populations. We report the use a P. falciparum CHMI model candidates, using their impact multiplication rate (PMR) as primary end point. Methods....
Malaria continues to be one of the world's most devastating infectious tropical diseases, and alternative strategies prevent infection disease spread are urgently needed. These include development effective vaccines, such as malaria transmission blocking vaccines (TBV) directed against proteins found on sexual stages Plasmodium falciparum parasites present in mosquito midgut. The Pfs25 protein, which is expressed surface gametes, zygotes ookinetes, has been a primary target for TBV...
Abstract Malaria transmission-blocking vaccines (TBVs) target the development of Plasmodium parasites within mosquito, with aim preventing malaria transmission from one infected individual to another. Different vaccine platforms, mainly protein-in-adjuvant formulations delivering leading candidate antigens, have been developed independently and reported varied activities (TBA). Here, recombinant chimpanzee adenovirus 63, ChAd63 modified vaccinia virus Ankara, MVA, expressing AgAPN1,...