The Zika virus is one of a group of viruses (the flavivirus) which are transmitted by insects and related animals. It was first discovered in the Zika Forest in Uganda in 1947, but it is currently an emerging infection across the Americas. There is currently no vaccine to prevent Zika infection, and no specific drug to treat it. Evidence of the molecular pathology, cellular physiology and immunology of the virus is also scarce.
A Zika Virus Vaccine Programme to respond to this epidemic threat has therefore been put into place at the University of Oxford: Professor Arturo Reyes-Sandoval and his research group from The Jenner Institute, Nuffield Department of Medicine, are prioritising the development of a Zika vaccine, with the aim of testing vaccine candidates in an early pre-clinical model in the next few months.
As part of the NDM-Mexico collaborative project, Professor Reyes-Sandoval has produced several memoranda of understanding with health Institutions and leading research universities in Mexico, with the aim of improving local research capacity, and opening up access to a vast number of patient samples in Mexico. This capability is currently being used to better understand the immunobiology of the Zika virus. This information will in turn inform vaccine development.
About the Zika virus
Zika is transmitted in humans by Aedes mosquitoes that have acquired the virus by feeding on an infected person. From its initial identification in 1947, two genetically distinct lineages (Asian and African) of the virus have now been reported. The Zika virus causes an illness similar to that caused by the related dengue virus. Symptoms include fever, a characteristic skin rash and conjunctivitis, as well as headache, vomiting and muscle pain. Reports of severe illness and fatalities from Zika virus infections are rare.
Most worrying, infection with the Zika virus may lead to microcephaly in newborns: about 4,180 cases of microcephaly have been identified in Brazil so far, and numbers are continuing to rise, according to Zika Infection, a collaboration with ISARIC and colleagues at FIOCRUZ, WHO, Institut Pasteur, ERASMUS, PREDEMICS, ANTIGONE, iDAMS, PREPARE Europe, REACTing (Aviesan), and the German Centre for Infection Research (Institute of Virology – University of Bonn Medical Centre) hosted on The Global Health Network. Zika virus infections have also been reported in many countries in Asia, the Americas and Europe, but most cases are currently occurring in Latin America, including in Mexico, Ecuador, Colombia, Venezuela, El Salvador, Brazil, French Giuiana, Guatemala, Honduras, Panama, Paraguay, Haiti, Martinique and Puerto Rico.
Dengue is caused by any one out of four dengue virus serotypes transmitted by mosquitoes. These serotypes infect up to 400 million people a year being the leading cause of illness and death in the tropics and subtropics. Dengue incidence is geographically expanding due to host migration, environmental changes and adaptability of mosquitoes. This makes dengue virus the most important mosquito-borne viral pathogen in the world. To date, there is no licensed vaccine yet available despite various vaccines currently under development in the world.
A huge challenge in vaccine development is to design effective vaccines against variable pathogens, such as dengue virus (DENV). 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). Over the last two years, our laboratory has integrated a range of novel technologies to develop a DENV vaccine with the ability to address pathogen diversity.
To investigate whether our new immunogen is truly universal, we have established a consortium in Mexico to isolate and preserve samples from patients previously infected with dengue. These will be important to determine if immune cells recognise our immunogen regardless of the dengue serotype the HLA of the volunteers.
Plasmodium vivax is the world's most widely distributed human malaria parasite. Estimates suggest that 2.5 billion people are at risk of infection and nearly 400 million clinical episodes occur annually. P. vivax endemicity is highest in Asia and Asia-Pacific, which contribute 84% of the global population at risk, or 2 billion people. Infection is also endemic in the Americas. As yet, there is no licensed vaccine and no other vaccine candidate in development that could prevent malaria infection. Our research group has been collaborating with Dr Lilia González-Cerón at the Centro Regional de Investigación en Salud Pública (CRISP) and Instituto Nacional de Salud Pública(INSP) , who has collaborated with us to assess immune responses against isolates of the P. vivax parasite from Mexico.
Chikungunya virus is an arthropod-borne alphavirus that have recently emerged to inflict major outbreaks and economical burden. CHIKV are highly prevalent in the Americas and expanding rapidly. Chikungunya is considered a health problem and a pandemic threat. To date, there are no licenced vaccines to tackle Chikungunya virus. Our consortium in Mexico is supporting the isolation and preservation of samples from patients infected with chikungunya virus. These samples will be used to inform vaccine development as one of the major preventive measures to control the disease.
Chagas disease (caused by Trypanosoma cruzi) remains a leading neglected tropical disease in the Americas. Approximately 7.5 million people are living with Chagas disease, mostly in poor regions of Central and South America, although thousands of T. cruzi-infected individuals also live in the United States and different European countries. This infection is associated with 546,000 disability adjusted life years and 10,300 annual deaths. There is no a licensed vaccine yet on the market and our group is currently working towards the development of a chagas vaccine