Vaccine
Examples of vaccine projects previously funded by Technology Transfer. See other areas.
Strategic Translation Award
Acceleration of the development of vaccines and diagnostics for typhoid fever using a human challenge model
Typhoid is a serious infection which kills up to 600,000 people every year. Many children and adults are affected by the disease and it is the commonest bacterial cause of fever in children attending hospital in some parts of South Asia.
It is very expensive to undertake the field studies that are needed to see if new vaccines work and this has stalled development of some new generation vaccines which might give better protection against typhoid. In this project a research team lead by Professor Andrew Pollard from Oxford University will use a model of infection in healthy volunteers to see if a new vaccine can prevent the disease. The researchers will also use the model to understand typhoid infection better and study which components of immunity are important in vaccine protection. The team will use the model to try to develop new blood or urine tests for better diagnosis of typhoid. It is hoped that these studies will improve case management and move vaccine development more quickly to eventually save lives.
It is very expensive to undertake the field studies that are needed to see if new vaccines work and this has stalled development of some new generation vaccines which might give better protection against typhoid. In this project a research team lead by Professor Andrew Pollard from Oxford University will use a model of infection in healthy volunteers to see if a new vaccine can prevent the disease. The researchers will also use the model to understand typhoid infection better and study which components of immunity are important in vaccine protection. The team will use the model to try to develop new blood or urine tests for better diagnosis of typhoid. It is hoped that these studies will improve case management and move vaccine development more quickly to eventually save lives.
Strategic Translation Award
Establishment of stability, preclinical immunogenicity and safety of low dose IPV adjuvanted with commercial oil in water emulsion
Exploratory preclinical studies have suggested that oil in water emulsions can permit the use of reduced doses of inactivated polio vaccine. This could facilitate immunisation against polio in areas where the OPV vaccine is poorly effective as well as enabling broad immunisation after OPV cessation.
Dr Patrice Dubois from the Vaccine Formulation Laboratory at the University of Lausanne and colleagues have been awarded translational funding to generate supporting data for the evaluation of this concept in clinical trials as well as determining the feasibility of multi dose vial formats containing a preservative to enable vaccination in resource poor settings. The clinical studies following this project will be conducted in India to confirm the immunogenicity of the reduced dose adjuvant vaccine in a paediatric population. The Vaccine Formulation Laboratory is a WHO Collaborating Center established to provide training and access to adjuvant technology to the public sector and developing countries vaccine manufacturers.
Dr Patrice Dubois from the Vaccine Formulation Laboratory at the University of Lausanne and colleagues have been awarded translational funding to generate supporting data for the evaluation of this concept in clinical trials as well as determining the feasibility of multi dose vial formats containing a preservative to enable vaccination in resource poor settings. The clinical studies following this project will be conducted in India to confirm the immunogenicity of the reduced dose adjuvant vaccine in a paediatric population. The Vaccine Formulation Laboratory is a WHO Collaborating Center established to provide training and access to adjuvant technology to the public sector and developing countries vaccine manufacturers.
Strategic Translation Award
Development of a PorA / FetA protein vaccine to prevent meningococcal disease
Meningitis B is the leading cause of bacterial meningitis and septicaemia in the UK causing up to 1500 cases each year and is the leading infectious cause of death in childhood.
Development of a vaccine has been hampered by the lack of immunogenicity of various antigens as well as the variability of the proteins between strains. Professor Andrew Pollard and Professor Martin Maiden at University of Oxford with Professor Jeremy Derrick (Manchester University) and Professor Ian Feavers (National Institute for Biological Standards and Control) have been awarded a Translation Award to develop a promising meningococcal vaccine candidate based on the structuring of surface proteins within hyperinvasive lineages, taking a vaccine composed of a combination of the PorA (porin), and FetA (iron-regulated surface protein) proteins from pre-clinical studies to Phase I clinical trials in humans.
Development of a vaccine has been hampered by the lack of immunogenicity of various antigens as well as the variability of the proteins between strains. Professor Andrew Pollard and Professor Martin Maiden at University of Oxford with Professor Jeremy Derrick (Manchester University) and Professor Ian Feavers (National Institute for Biological Standards and Control) have been awarded a Translation Award to develop a promising meningococcal vaccine candidate based on the structuring of surface proteins within hyperinvasive lineages, taking a vaccine composed of a combination of the PorA (porin), and FetA (iron-regulated surface protein) proteins from pre-clinical studies to Phase I clinical trials in humans.
Strategic Translation Award
Testing a new TB vaccine for potential efficacy in South African infants
TB is one of the world’s biggest killers, causing around 2 million deaths per year, with South Africa being one of the most affected countries. The current vaccine (BCG) is not very effective, especially against lung disease; therefore, MVA85A is designed to enhance the immune response to BCG. The Phase IIb trial in South Africa is due to start shortly and will be the first of the new generation of TB vaccines to enter into trials testing for efficacy. It will involve around 2800 BCG-vaccinated infants, half of whom will receive MVA85A and half of whom will receive a placebo vaccine. The infants will then be followed up for two years to monitor rates of TB in both groups. This trial is being run in collaboration with OETC, the South African TB Vaccine Initiative (SATVI) and the Aeras Global TB Vaccine Foundation, who will be the trial sponsor.
Dr Helen McShane at the University of Oxford and the Oxford-Emergent Tuberculosis Consortium have received an award to part-fund the first trial of the new TB vaccine candidate, MVA85A.
TB is one of the world’s biggest killers, causing around 2 million deaths per year, with South Africa being one of the most affected countries. The current vaccine (BCG) is not very effective, especially against lung disease; therefore, MVA85A is designed to enhance the immune response to BCG. The Phase IIb trial in South Africa is due to start shortly and will be the first of the new generation of TB vaccines to enter into trials testing for efficacy. It will involve around 2800 BCG-vaccinated infants, half of whom will receive MVA85A and half of whom will receive a placebo vaccine. The infants will then be followed up for two years to monitor rates of TB in both groups. This trial is being run in collaboration with OETC, the South African TB Vaccine Initiative (SATVI) and the Aeras Global TB Vaccine Foundation, who will be the trial sponsor.
See our video: Fighting to end tuberculosis
Strategic Translation Award
Development of an oral adenovirus-based vaccine against influenza
To develop this vaccine PaxVax has adapted an oral adenovirus vaccine that has been used safely in 10 million U.S. military personnel over 30 years to protect them against adenovirus related respiratory illness. PaxVax has modified the adenovirus component of the vaccine such that it makes influenza proteins. The vaccine is prepared as an enteric coated capsule which passes the stomach and delivers live adenovirus particles to the small intestine causing immunity to influenza. With Wellcome Trust support PaxVax is performing a clinical trial of an influenza H5N1 (Bird Flu) vaccine. The trial is designed to assess the vaccine's safety in approximately 120 subjects and to measure antibody, cellular and mucosal immunity at a range of different doses.
PaxVax has received a Strategic Award to develop an orally delivered vaccine to protect people against pandemic strains of influenza. Most influenza vaccines in use today are injections requiring needles, sterile techniques and liquids.
To develop this vaccine PaxVax has adapted an oral adenovirus vaccine that has been used safely in 10 million U.S. military personnel over 30 years to protect them against adenovirus related respiratory illness. PaxVax has modified the adenovirus component of the vaccine such that it makes influenza proteins. The vaccine is prepared as an enteric coated capsule which passes the stomach and delivers live adenovirus particles to the small intestine causing immunity to influenza. With Wellcome Trust support PaxVax is performing a clinical trial of an influenza H5N1 (Bird Flu) vaccine. The trial is designed to assess the vaccine's safety in approximately 120 subjects and to measure antibody, cellular and mucosal immunity at a range of different doses.
The potential advantages of PaxVax oral vaccines compared to traditional injectable vaccines for recipients include convenience, ease of administration and lower costs. The advantages of such flu vaccines for society at large include faster manufacturing, ease of stockpiling, more rapid distribution to the needy and lower costs.
Strategic Translation Award
The safety and immunogenicity of a single-dose oral typhoid vaccine
Emergent Biosystems UK Ltd aims to clinically evaluate their vaccine, already tested in studies in the UK and US, on healthy Vietnamese adults and children. In conjunction with the Wellcome Trust programme led by Dr Jeremy Farrar in Vietnam, there are also plans to set up a field site in the Mekong Delta region where future phase II and III studies can be carried out to assess whether the vaccine protects against typhoid fever following natural exposure.
Typhoid fever remains a major disease in low- and middle-income countries. There is currently no available affordable vaccine that offers long-term protection after a single dose.
Emergent Biosystems UK Ltd aims to clinically evaluate their vaccine, already tested in studies in the UK and US, on healthy Vietnamese adults and children. In conjunction with the Wellcome Trust programme led by Dr Jeremy Farrar in Vietnam, there are also plans to set up a field site in the Mekong Delta region where future phase II and III studies can be carried out to assess whether the vaccine protects against typhoid fever following natural exposure.
See also: Malaria Vaccine Trials: tuberculosis, Down in one: Developing a single-dose, drinkable typhoid vaccine
Strategic Translation Award
Conjugate vaccine for typhoid fever caused by the bacteria Salmonella enterica serovars Typhi and Paratyphi A
Currently, there are over 21 million cases of typhoid fever worldwide with no affordable vaccine available offering long-term protection.
The highest incidence of cases and deaths occur in children of low- and middle-income countries, predominantly in the Indian subcontinent and in South-East Asia. Current antibiotics, once an effective means of treatment, are becoming less useful due to increasing drug resistance. In conjunction with the Wellcome Trust, the Novartis Vaccines Institute for Global Health aims to combat that by leveraging its knowledge from research and development in conjugate vaccines for the development of a bivalent vaccine that protects against both S.Typhi and S.Paratyphi A; two very similar illness which - if left untreated - can result in complications and death, particularly in young children and the immuno-compromised. Such a vaccine will target molecules on the surface of the bacteria, which will be made more immunogenic by linking them with a protein carrier that is used in many childhood vaccines. The NVGH research will build upon a promising prototype conjugate vaccine developed by the National Institutes of Health. The research team, led by Dr Laura Martin, aims to have a product ready for clinical trials by the end of 2010. This vaccine will be tested in Europe first and subsequently in the low- and middle-income countries where it is most needed.
The highest incidence of cases and deaths occur in children of low- and middle-income countries, predominantly in the Indian subcontinent and in South-East Asia. Current antibiotics, once an effective means of treatment, are becoming less useful due to increasing drug resistance. In conjunction with the Wellcome Trust, the Novartis Vaccines Institute for Global Health aims to combat that by leveraging its knowledge from research and development in conjugate vaccines for the development of a bivalent vaccine that protects against both S.Typhi and S.Paratyphi A; two very similar illness which - if left untreated - can result in complications and death, particularly in young children and the immuno-compromised. Such a vaccine will target molecules on the surface of the bacteria, which will be made more immunogenic by linking them with a protein carrier that is used in many childhood vaccines. The NVGH research will build upon a promising prototype conjugate vaccine developed by the National Institutes of Health. The research team, led by Dr Laura Martin, aims to have a product ready for clinical trials by the end of 2010. This vaccine will be tested in Europe first and subsequently in the low- and middle-income countries where it is most needed.
Translation Awards
Novel vaccine against haemorrhagic septicaemia in cattle and buffalo for use by resource poor farmers
Haemorrhagic septicaemia (HS) is a bacterial disease that affects cattle, buffalo and camels across South Asia, Africa and South America. Transmission of the bacteria is airborne, but infection quickly leads to a systemic disease of the blood causing death of the animal within 24 hours.
In India, it is estimated that HS is responsible for approximately half of all bovine deaths. The disease is a significant economic problem for resource-poor farmers who tend to rely on these animals for meat, milk, draught power, manure and heat. A research consortium led by the Moredun Research Institute in Edinburgh has been set up to develop a vaccine to prevent this disease. Together with colleagues from the University of Glasgow, Indian Veterinary Research Institute, Global Alliance for Livestock Veterinary Medicines (GALVmed), Inocul8 Ltd and Indian Immunologicals Ltd, the team plan to weaken the causative bacterium so that it is unable to cause disease (after immunisation) but will trigger an immune response in the animal that will prevent subsequent infections. This vaccine is anticipated to be more effective, easier to administer and give longer protection than other vaccines currently on the market. The output of this work will be a prototype vaccine, adapted to the commercial manufacturing environment, and shown to be effective in controlling disease in a number of field evaluations across India.
In India, it is estimated that HS is responsible for approximately half of all bovine deaths. The disease is a significant economic problem for resource-poor farmers who tend to rely on these animals for meat, milk, draught power, manure and heat. A research consortium led by the Moredun Research Institute in Edinburgh has been set up to develop a vaccine to prevent this disease. Together with colleagues from the University of Glasgow, Indian Veterinary Research Institute, Global Alliance for Livestock Veterinary Medicines (GALVmed), Inocul8 Ltd and Indian Immunologicals Ltd, the team plan to weaken the causative bacterium so that it is unable to cause disease (after immunisation) but will trigger an immune response in the animal that will prevent subsequent infections. This vaccine is anticipated to be more effective, easier to administer and give longer protection than other vaccines currently on the market. The output of this work will be a prototype vaccine, adapted to the commercial manufacturing environment, and shown to be effective in controlling disease in a number of field evaluations across India.
Translation Award
Structurally modified master seed viruses to enhance conventional foot-and-mouth disease virus vaccine production
Despite success in the developed world, major problems limit the capacity of FMDV vaccines to control infections in low- and middle-income countries. The virus is notoriously unstable which can reduce the yield and effectiveness of the vaccine and increases production costs.
Furthermore, FMD viruses are highly variable, necessitating the frequent development of new vaccine strains. Vaccine production requires the adaption of a field virus to growth in cultured cells which can be time consuming, reduce vaccine yield and select undesired antigenic changes in the virus shell. Live modified viruses can be recovered and inactivated to produce vaccine in the conventional manner. Bryan Charleston at the Institute of Animal Health, in partnership with collaborators from Oxford, Onderstepoort (South Africa), Plum Island (USA) and Intervet has been awarded translational funding to adapt available technology for use in industrial scale production, to produce and market FMD vaccines with enhanced stability and customised to protect against currently circulating viruses.
Furthermore, FMD viruses are highly variable, necessitating the frequent development of new vaccine strains. Vaccine production requires the adaption of a field virus to growth in cultured cells which can be time consuming, reduce vaccine yield and select undesired antigenic changes in the virus shell. Live modified viruses can be recovered and inactivated to produce vaccine in the conventional manner. Bryan Charleston at the Institute of Animal Health, in partnership with collaborators from Oxford, Onderstepoort (South Africa), Plum Island (USA) and Intervet has been awarded translational funding to adapt available technology for use in industrial scale production, to produce and market FMD vaccines with enhanced stability and customised to protect against currently circulating viruses.
Translation Award
Therapeutic CD8+ T cell-biased vaccines for human visceral leishmaniasis
Visceral leishmaniasis leads to approximately 70 000 reported deaths annually (though actual deaths are estimated at 4-5 times this figure).
Visceral leishmaniasis is caused by infection with the protozoan parasites Leishmania donovani and L.infantum. With resistance against existing treatments high or developing, and affordable second-line treatments limited, the development of new preventative and/or therapeutic measures is a major international research priority. In spite of much effort, CD4+ T cell-biased vaccines have so far failed to deliver significant levels of protective immunity in man. An international research team, led by Professor Paul Kaye at the University of York has been awarded funding to develop a novel therapeutic vaccine for visceral leishmaniasis, targeting the induction/re-activation of CD8+ T cells. The study will identify the most appropriate molecule/vector combination and confirm safety in UK volunteers. This study is an essential step in the process of developing a new vaccine, to reduce deaths from visceral leishmaniasis.
Visceral leishmaniasis is caused by infection with the protozoan parasites Leishmania donovani and L.infantum. With resistance against existing treatments high or developing, and affordable second-line treatments limited, the development of new preventative and/or therapeutic measures is a major international research priority. In spite of much effort, CD4+ T cell-biased vaccines have so far failed to deliver significant levels of protective immunity in man. An international research team, led by Professor Paul Kaye at the University of York has been awarded funding to develop a novel therapeutic vaccine for visceral leishmaniasis, targeting the induction/re-activation of CD8+ T cells. The study will identify the most appropriate molecule/vector combination and confirm safety in UK volunteers. This study is an essential step in the process of developing a new vaccine, to reduce deaths from visceral leishmaniasis.