Ian Poulton
A5040896653- Malaria Research and Control
- Mosquito-borne diseases and control
- HIV Research and Treatment
- Tuberculosis Research and Epidemiology
- Immunodeficiency and Autoimmune Disorders
- SARS-CoV-2 and COVID-19 Research
- vaccines and immunoinformatics approaches
- Viral Infections and Outbreaks Research
- Hepatitis B Virus Studies
- Immunotherapy and Immune Responses
- Viral Infections and Vectors
- Mycobacterium research and diagnosis
- Immune responses and vaccinations
- Virus-based gene therapy research
- Complement system in diseases
- COVID-19 Clinical Research Studies
- Viral gastroenteritis research and epidemiology
- Parasites and Host Interactions
- Vector-borne infectious diseases
- Herpesvirus Infections and Treatments
- Animal Virus Infections Studies
- Diphtheria, Corynebacterium, and Tetanus
- Research on Leishmaniasis Studies
- Cancer Immunotherapy and Biomarkers
- Prostate Cancer Treatment and Research
Jenner Institute
2016-2025
University of Oxford
2016-2025
Churchill Hospital
2007-2025
AstraZeneca (Brazil)
2021
Chinese Academy of Medical Sciences & Peking Union Medical College
2021
NIHR Clinical Research Network
2021
Oxford BioMedica (United Kingdom)
2020
Hospital for Tropical Diseases
2016
National Institute for Health Research
2015
Oxford Biomedical Research
2015
The West African outbreak of Ebola virus disease that peaked in 2014 has caused more than 11,000 deaths. development an effective vaccine is a priority for control future outbreak.
Abstract Induction of antigen-specific CD8 + T cells offers the prospect immunization against many infectious diseases, but no subunit vaccine has induced that correlate with efficacy in humans. Here we demonstrate a replication-deficient chimpanzee adenovirus vector followed by modified vaccinia virus Ankara booster induces exceptionally high frequency T-cell responses (median >2400 SFC/10 6 peripheral blood mononuclear cells) to liver-stage Plasmodium falciparum malaria antigen ME-TRAP....
SummaryBackgroundCases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection continue to rise in the Arabian Peninsula 7 years after it was first described Saudi Arabia. MERS-CoV poses a significant risk public health security because an absence currently available effective countermeasures. We aimed assess safety and immunogenicity candidate simian adenovirus-vectored vaccine expressing full-length spike surface glycoprotein, ChAdOx1 MERS, humans.MethodsThis dose-escalation,...
Background.Vaccine development in human Plasmodium falciparum malaria has been hampered by the exceptionally high levels of CD8 1 T cells required for efficacy.Use potently immunogenic adenoviruses as vaccine vectors could overcome this problem, but these are limited preexisting immunity to adenoviruses.Methods.From 2007 2010, we undertook a phase I dose and route finding study new vaccine, replication-incompetent chimpanzee adenovirus 63 (ChAd63) encoding preerythrocytic insert multiple...
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...
Intranasal vaccination may induce protective local and systemic immune responses against respiratory pathogens. A number of intranasal SARS-CoV-2 vaccine candidates have achieved protection in pre-clinical challenge models, including ChAdOx1 nCoV-19 (AZD1222, University Oxford / AstraZeneca).We performed a single-centre open-label Phase I clinical trial with healthy adults, using the existing formulation produced for intramuscular administration. Thirty vaccine-naïve participants were...
Malaria is a major global health problem for which an effective vaccine required urgently. Prime-boost vaccination regimes involving plasmid DNA and recombinant modified vaccinia virus Ankara-encoding liver-stage malaria antigens have been shown to be powerfully immunogenic T cells capable of inducing partial protection against experimental challenge in humans, manifested as delay time patent parasitemia. Here, we report that substitution the priming vector with specific attenuated fowlpox...
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...
The safety, immunogenicity, and efficacy of DNA modified vaccinia virus Ankara (MVA) prime-boost regimes were assessed by using either thrombospondin-related adhesion protein (TRAP) with a multiple-epitope string ME (ME-TRAP) or the circumsporozoite (CS) Plasmodium falciparum. Sixteen healthy subjects who never had malaria (malaria-naive subjects) received two priming vaccinations DNA, followed one boosting immunization MVA, ME-TRAP CS as antigen. Immunogenicity was ex vivo gamma interferon...
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,...
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....
Background. Circumsporozoite protein (CS) is the antigenic target for RTS,S, most advanced malaria vaccine to date. Heterologous prime-boost with viral vectors simian adenovirus 63 (ChAd63)-modified vaccinia virus Ankara (MVA) potent inducer of T-cells in humans, demonstrating significant efficacy when expressing preerythrocytic antigen insert multiple epitope–thrombospondin-related adhesion (ME-TRAP). We hypothesized that ChAd63-MVA containing CS may result a clinical protective efficacy.
Over a century since Ronald Ross discovered that malaria is caused by the bite of an infectious mosquito it still unclear how number parasites injected influences disease transmission. Currently assumed all mosquitoes with salivary gland sporozoites are equally irrespective they harbour, though this has never been rigorously tested. Here we analyse >1000 experimental infections humans and mice demonstrate dose-dependency for probability infection length host pre-patent period. Mosquitoes...
There is currently no safe human challenge model of Mycobacterium tuberculosis infection to enable proof-of-concept efficacy evaluation candidate vaccines against tuberculosis. In vivo antimycobacterial immunity could be assessed using intradermal bovis bacille Calmette-Guérin (BCG) vaccination as a surrogate for M. infection.Healthy BCG-naive and BCG-vaccinated volunteers were challenged with BCG. BCG load was quantified from skin biopsy specimens by polymerase chain reaction (PCR) culture...
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....
Plasmodium vivax is the most widespread human malaria geographically; however, no effective vaccine exists. Red blood cell invasion by P. merozoite depends on an interaction between Duffy antigen receptor for chemokines (DARC) and region II of parasite's Duffy-binding protein (PvDBP_RII). Naturally acquired binding-inhibitory antibodies against this associate with clinical immunity, but it unknown whether these responses can be induced vaccination.Safety immunogenicity replication-deficient...
Background. The need for a highly efficacious vaccine against Plasmodium falciparum remains pressing. In this controlled human malaria infection (CHMI) study, we assessed the safety, efficacy and immunogenicity of schedule combining 2 distinct types in staggered immunization regimen: one inducing high-titer antibodies to circumsporozoite protein (RTS,S/AS01B) other potent T-cell responses thrombospondin-related adhesion (TRAP) by using viral vector. Method. Thirty-seven healthy malaria-naive...
There are no licensed vaccines against Plasmodium vivax. We conducted two phase 1/2a clinical trials to assess targeting P. vivax Duffy-binding protein region II (PvDBPII). Recombinant viral using chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) vectors as well a adjuvant formulation (PvDBPII/Matrix-M) were tested in both standard delayed dosing regimen. Volunteers underwent controlled human malaria infection (CHMI) after their last vaccination, alongside...
An effective new tuberculosis (TB) vaccine regimen must be safe in individuals with latent TB infection (LTBI) and is a priority for global health care.To evaluate the safety immunogenicity of leading vaccine, recombinant Modified Vaccinia Ankara expressing Antigen 85A (MVA85A) LTBI.An open-label, phase I trial MVA85A was performed 12 subjects LTBI recruited from contact clinics Oxford London or by poster advertisements hospitals. Patients were assessed clinically had blood samples drawn...
BackgroundPrevious research indicates that a combination vaccine targeting different stages of the malaria life cycle is likely to provide most effective vaccine. This trial was first combine two existing vaccination strategies produce induces immune responses both pre-erythrocytic and blood P. falciparum cycle.MethodsThis Phase I/IIa study new FFM ME-TRAP+PEV3A. PEV3A includes peptides from circumsporozoite protein blood-stage antigen AMA-1. conducted at Centre for Clinical Vaccinology...
Background Inhibition of parasite growth is a major objective blood-stage malaria vaccines. The in vitro assay inhibitory activity (GIA) widely used as surrogate marker for vaccine efficacy the down-selection candidate Here we report first study to examine relationship between vivo Plasmodium falciparum rates and GIA humans experimentally infected with malaria. Methods In this phase I/IIa open-label clinical trial five healthy malaria-naive volunteers were immunised AMA1/C1-Alhydrogel+CPG...
Background Controlled human malaria infection (CHMI) studies have become a routine tool to evaluate efficacy of candidate anti-malarial drugs and vaccines. To date, CHMI trials mostly been conducted using the bite infected mosquitoes, restricting number trial sites that can perform studies. Aseptic, cryopreserved P. falciparum sporozoites (PfSPZ Challenge) provide potentially more accurate, reproducible practical alternative, allowing known be administered simply by injection. Methodology We...