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cesar-camacho-and-fabiana-leoratti-in-arturo-s-lab.jpg1. Plasmodium vivax malaria: Development of a novel vaccine against Plasmodium vivax malaria using adenovirus of chimpanzee origin and Modified Vaccinia Ankara (MVA) as recombinant vaccines

This project is in collaboration with:

Leiden University Medical Center: Dr. Chris J. Janse, Head of the Leiden Malaria Research Group, Parasitology, Center of Infectious Diseases, Leiden University Medical Center (LUMC), and Dr Shahid M. Khan, Leiden Malaria Research Group, Leiden University Medical Center, Department of Parasitology, Netherlands.

National Institute of Public Health: Dr Lilia González-Cerón, Regional Research Centre on Public Health of the National Institute of Public Health (Centro Regional de Investigación en Salud Pública, Instituto Nacional de Salud Pública, CRISP-INSP) Tapachula, Chiapas, México.

Inspired by the Gates malaria forum in 2007, the goal to eradicate malaria has come back to the global health agenda 40 years after the initial commitment by the WHO to eradicate this disease and thus, efforts to prevent and cure the most prevalent and neglected form of malaria caused by P. vivax will increase as a result of this renewed interest. P. vivax is the most widely distributed human malaria, representing the major cause of this disease outside Africa. It is considered that this parasite threatens nearly 40% of the human population.

The aim of this project is to develop a vaccine against the pre-erythrocytic stages of P. vivax parasites using a leading strategy that has proved successful for P. falciparum vaccine development: the use of recombinant chimpanzee adenoviral vector ChAd63 and MVA to induce strong T-cell responses, as well as the use of virus-like particles (VLPs) to stimulate antibody responses. We will target the pre-erythrocytic stage antigens circumsporozoite protein (CS) and thrombospondin related adhesion protein (TRAP), both of which have a central role in hepatocyte invasion by malaria sporozoites injected by mosquitoes.

This project is supported by the Wellcome Trust

mosquitoes-in-arturo-s-lab.jpg2. Dengue: Development of a universal T-cell vaccine against dengue virus infection

This project is in collaboration with:

Oxford University Clinical Research Unit in Vietnam, OUCRU: Professor Cameron Simmons, NDM, University of Oxford

Universidade Federal de Minas Gerais: Dr Flávio Guimarães da Fonseca, Microbiology Department, ICB - UFMG, Brasil

Benemérita Universidad Autónoma de Puebla: Dr Rosa Rocha Gracia and Dr Miguel Garcia Knight, Research Center in Microbiological Sciences, Sciences Institute, BUAP, México

Universidad Michoacana de San Nicolás de Hidalgo: Professor Martha Eva Viveros Sandoval, Head of Laboratorio de Hemostasia y Biología Vascular, “Dr. Ignacio Chávez” School of Medicine, UMNSH, México

Laboratorio Estatal de Salud Pública, Michoacán (LESP): MSP Gloria Alicia Figueroa Aguilar, Head of Public Health State Laboratory of Michoacán and MSP Wendy Vianey Padilla Cabrera, Coordinator of Epidemiology of the Public Health State Laboratory, Michoacán, México

Dengue is a re-emerging infectious disease of major global importance, representing an enormous burden for health care systems in endemic countries. A huge challenge in vaccine development is to design effective vaccines against variable pathogens, such as dengue virus (DENV). Pathogen variability means they are able to induce changes in their structure overtime allowing them to be more diverse and efficient. Dengue disease, transmitted by mosquitoes, can be caused by any of four different DENV serotypes. Exposure and infection with one serotype confers immunity against that specific serotype but not to the other three remaining serotypes. Moreover, studies have shown patients that previously suffered from dengue are in high risk to develop a more aggressive form of the disease if they come into contact with a different DENV serotype; a process known as Antibody-Dependent Enhancement (ADE). The aim of this project is to develop a universal vaccine able to induce protective immunity against all DENV serotypes. To this end, our team will develop methodologies to elicit immune responses against the most conserved viral epitopes and proteins, through the use of viral-vectored and VLP immunisation.

This project is supported by IDAMS-FP7, Oxford Martin School, MRC Confidence in Concept

blood-sample.png3. Dengue: A study of cellular immune responses in humans against dengue virus (DENV) to inform vaccine development.

This project is in collaboration with:

Laboratorio Estatal de Salud PúblicaSecretaria de Salud, Morelia, Michoacán, México

Laboratorio de Salud Pública, Jurisdicción Número 8, Lázaro Cárdenas, México

Universidad Michoacana San Nicolás de Hidalgo, México

Benemérita Universidad Autónoma de Puebla, México

Vaccines save about 2.5 million lives every year; highly effective vaccines against variable pathogens such as dengue virus (DENV) could double this number. Dengue is the most rapidly spreading mosquito-borne viral disease in the world; current estimates indicate an astonishing 390 million infections every year, with Mexico presenting 6.3% of the cases. Dengue affects a large number of people from a substantial at-risk population, and hampers social and economic development, both in Mexico and worldwide.

Despite ongoing research, there are currently no licensed vaccines to prevent dengue infection. Most DENV vaccines in clinical development aim to induce protective antibodies to cover all four serotypes of the virus, but have shown disappointing efficacy. A novel approach, developed by Arturo Reyes-Sandoval's group, aims to stimulate the T-cell response, the other branch of the immune system. This approach targets the Achilles heel of the dengue virus: its most essential and conserved parts, which do not change regardless of serotype. We have developed a bioinformatics approach to uncover the most conserved parts of DENV, and have designed an immunogen to be used as a universal vaccine to protect against all four strains.

We are currently investigating whether this immunogen is truly universal. To address this question, we will establish the infrastructure and lay the basis to allow an analysis of blood samples from infected people living in diverse areas of Mexico, and determine if their immune system reacts against the newly developed dengue immunogen. This proposal will support establishing a network to create and support the environment for the study.

This project is supported by Newton Fund-British Council and CONACyT

erandeni-at-the-ndm-lab.jpg4. Chagas: Pre-clinical protective efficacy of novel Chagas vaccine candidates: A final step towards clinical application

This project is in collaboration with:

London School of Hygiene and Tropical Medicine: Professor John M. Kelly, Department of Pathogen Molecular Biology, LSHTM

Chagas disease, caused by Trypanosoma cruzi remains a neglected tropical disease in the Americas, affecting approximately 7.5 million people. An efficacious vaccine would be a major, cost-effective approach to improving public health in the Americas.

Two leading Chagas vaccine antigens have been used to develop MVA and adenoviral vectored vaccines at the Jenner Institute. The vaccine candidates induced outstanding immunogenicity in mice and we are joining efforts with Prof. John Kelly’s group, leading various LSHTM scientists to assess protective efficacy using novel transgenic parasites developed in this institution.

Efficacy demonstration will be key for translation to a clinical trial.

This project is supported by MRC-DPFS scheme

 dr-hancock-and-msp-wendy-working-hard-in-the-lab.jpg5. Development of new vaccines for therapy of high-risk Human Papillomavirus infections

This project is in collaboration with:

Professor Lucy Dorrell, Associate Professor, Senior Clinical Research Fellow and Honorary Consultant in Genitourinary / HIV Medicine at the Nuffield Department of Medicine

Human papillomaviruses (HPV) are responsible for virtually all cases of cervical cancer and a significant proportion of other anogenital and oropharyngeal cancers. Half a million cases of cervical cancer occur each year in low and middle income countries, largely due to the lack of cytological screening programmes. Licensed HPV vaccines are highly effective in preventing incident infection and consequent pre-malignant disease and could substantially reduce cervical cancers in resource-poor setting if widely implemented. However, there remains a gap in coverage for the millions of women already persistently infected with high-risk HPV. In addition, there is a lack of effective screening for other HPV-driven anogenital cancers.

HPV is an attractive target for immunotherapeutic approaches to induce or enhance cell-mediated immunity and thus eliminate persistent infection and / or induce regression of dysplastic lesions. However, approaches tested to date have had modest potency and have focused on only one or two high-risk (HR) genotypes. In collaboration with Dr Nicola Ternette at the Jenner Institute and TDI Mass Spectrometry Laboratory, we are aiming to screen MHC-associated peptide sequences presented on primary HPV-driven anogenital cancer tissues for suitable T cell targets. Identified antigen candidates will then be selected and evaluated for their suitability in immunotherapeutic approaches for distinct HR genotypes by implementing them into viral vectors in collaboration with Dr Arturo Reyes-Sandoval at the Jenner Institute.

This project is supported by Oxford Cancer Research Centre Development Fund, Cancer Research UK and MRC Confidence in Concept