Yrene Themistocleous
A5103098667- Malaria Research and Control
- SARS-CoV-2 and COVID-19 Research
- Mosquito-borne diseases and control
- COVID-19 Clinical Research Studies
- Complement system in diseases
- COVID-19 epidemiological studies
- vaccines and immunoinformatics approaches
- Vaccine Coverage and Hesitancy
- Animal Virus Infections Studies
- Viral gastroenteritis research and epidemiology
- Immunotherapy and Immune Responses
- HIV Research and Treatment
- Parasites and Host Interactions
- Diphtheria, Corynebacterium, and Tetanus
- Antifungal resistance and susceptibility
- Virology and Viral Diseases
- COVID-19 and healthcare impacts
- COVID-19 and Mental Health
- Clostridium difficile and Clostridium perfringens research
- Insect and Pesticide Research
- Invertebrate Immune Response Mechanisms
- Immune responses and vaccinations
- Cancer Immunotherapy and Biomarkers
- Meta-analysis and systematic reviews
- Zoonotic diseases and public health
Jenner Institute
2020-2025
University of Oxford
2020-2025
UK Health Security Agency
2021-2022
Older adults (aged ≥70 years) are at increased risk of severe disease and death if they develop COVID-19 therefore a priority for immunisation should an efficacious vaccine be developed. Immunogenicity vaccines is often worse in older as result immunosenescence. We have reported the immunogenicity novel chimpanzee adenovirus-vectored vaccine, ChAdOx1 nCoV-19 (AZD1222), young adults, now describe safety this wider range participants, including aged 70 years older.In report phase 2 component...
The duration and effectiveness of immunity from infection with vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are relevant to pandemic policy interventions, including the timing vaccine boosters.
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,...
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...
RH5 is a leading blood-stage candidate antigen for Plasmodium falciparum vaccine; however, its safety and immunogenicity in malaria-endemic populations are unknown.
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...
Controlled human malaria infection (CHMI) provides a highly informative means to investigate host-pathogen interactions and enable in vivo proof-of-concept efficacy testing of new drugs vaccines. However, unlike Plasmodium falciparum, well-characterized P. vivax parasites that are safe suitable for use modern CHMI models limited. Here, 2 healthy malaria-naive United Kingdom adults with universal donor blood group were safely infected clone from Thailand by mosquito-bite CHMI. Parasitemia...
Abstract Clinical immunity to malaria can reduce fever and lead asymptomatic infection but the underlying mechanisms remain unclear. To examine development of clinical immunity, we conducted a multi-cohort, repeat controlled human (CHMI) study with Plasmodium vivax , heterologous rechallenge P. falciparum . Malaria-naïve adults underwent CHMI up three times, at an interval 5 20 months, by administration red blood cells infected PvW1 clone. In final cohort study, subset participants 3D7...
Immunity to severe malaria is acquired quickly, operates independently of pathogen load, and represents a highly effective form disease tolerance. The mechanism that underpins tolerance remains unknown. We used human rechallenge model falciparum in which healthy adult volunteers were infected three times over 12 mo period track the development real-time. found parasitemia triggered hardwired innate immune response led systemic inflammation, pyrexia, hallmark symptoms clinical across first...
ABSTRACT Background Understanding the duration and effectiveness of infection vaccine-acquired SARS-CoV-2 immunity is essential to inform pandemic policy interventions, including timing vaccine-boosters. We investigated this in our large prospective cohort UK healthcare workers undergoing routine asymptomatic PCR testing. Methods assessed vaccine (VE) (up 10-months after first dose) infection-acquired by comparing time PCR-confirmed vaccinated unvaccinated individuals using a Cox...
In endemic settings it is known that natural malaria immunity gradually acquired following repeated exposures. Here we sought to assess whether similar acquisition of blood-stage would occur parasite exposure by controlled human infection (CHMI). We report the findings repeat homologous Plasmodium falciparum (3D7 clone) CHMI studies VAC063C (ClinicalTrials.gov NCT03906474) and VAC063 NCT02927145). total, 24 healthy, unvaccinated, malaria-naïve UK adult participants underwent primary followed...
BACKGROUNDThe biology of Plasmodium vivax is markedly different from that P. falciparum; how this shapes the immune response to infection remains unclear. To address shortfall, we inoculated human volunteers with a clonal field isolate and tracked their through convalescence.METHODSParticipants were injected intravenously blood-stage parasites dynamics in real time by quantitative PCR. Whole blood samples used for high dimensional protein analysis, RNA sequencing, cytometry flight, temporal...
There are no licensed vaccines against Plasmodium vivax , the most common cause of malaria outside Africa.We conducted two Phase I/IIa clinical trials to assess safety, immunogenicity and efficacy targeting region II P. Duffy-binding protein (PvDBPII). Recombinant viral (using ChAd63 MVA vectors) were administered at 0, 2 months or in a delayed dosing regimen (0, 17, 19 months), whilst protein/adjuvant formulation (PvDBPII/Matrix-M™) was monthly 1, months) 14 months). Delayed regimens due...
Abstract Immunity to severe malaria is acquired quickly, operates independently of pathogen load and represents a highly effective form disease tolerance. The mechanism that underpins tolerance remains unknown. We developed human re-challenge model falciparum in which healthy adult volunteers were infected three times over 12 month period track the development real-time. found parasitemia triggered hardwired emergency host response led systemic inflammation, pyrexia hallmark symptoms...
Abstract Background RH5 is the leading blood-stage candidate antigen for inclusion in a Plasmodium falciparum malaria vaccine, however, its safety profile and ability to induce functional immune responses malaria-endemic population are unknown. Characterising immunogenicity key refine progress next-generation RH5-based vaccines field efficacy assessment. Methods A Phase 1b, single-center, dose-escalation, age de-escalation, double-blind, randomized, controlled trial was conducted Bagamoyo,...
The biology of Plasmodium vivax is markedly different to that P. falciparum ; how this shapes the immune response infection remains unclear. To address shortfall, we inoculated human volunteers with a clonal field isolate and tracked their through convalescence. High dimensional protein RNA-seq data show triggers an acute phase shares remarkable overlap , suggesting hardwired emergency myeloid does not discriminate parasite species. We then used cytometry by time flight analyse fate function...
Abstract In endemic settings it is known that natural malaria immunity gradually acquired following repeated exposures. Here we sought to assess whether similar acquisition of blood-stage would occur parasite exposure by controlled human infection (CHMI). We report the findings a repeat homologous Plasmodium falciparum (3D7 clone) CHMI study (VAC063C; ClinicalTrials.gov NCT03906474 ). total, 24 healthy, unvaccinated, malaria-naïve UK adult participants underwent primary followed drug...
Abstract Controlled human malaria infection (CHMI) provides a highly informative means to investigate host-pathogen interactions and enable in vivo proof-of-concept efficacy testing of new drugs vaccines. However, unlike Plasmodium falciparum , well-characterized P. vivax parasites that are safe suitable for use modern CHMI models limited. Here, two healthy malaria-naïve UK adults with universal donor blood group were safely infected clone from Thailand by mosquito-bite CHMI. Parasitemia...