Despite therapeutic advances, the continued emergence and re-emergence of novel infectious pathogens can have devastating healthcare impacts. Increased global interdependence and the ease of human, animal and trade movements facilitate transmission and present multiple opportunities for pathogen spread.
There are a number of novel and dangerous pathogens with recognised pandemic potential, including but not limited to, Ebola, Marburg, Rift Valley fever, Lassa Fever, MERS-CoV, Nipah, and Crimean Congo haemorrhagic fever. It is widely recognised that the health of humans and animals are interdependent and a number of emerging infectious diseases have a robust animal reservoir, facilitating transmission. Effectively treating human disease will necessitate consideration of disease control in animal reservoirs.
At the Jenner Institute we are developing vaccines for a number of emerging pathogens with careful consideration of implications for veterinary cross-over. Some of the works are at the pre-clinical stage while others have progressed to clinical trials.
This DPhil represents an exciting opportunity to build on the current and innovative program of vaccine development for emerging and re-emerging pathogens while working in close collaboration with the Wellcome Trust major overseas research programme in Kilifi, Kenya.
Both specialised subject training and generic research capabilities will be developed.
Including but not limited to:
All students will be expected to analyse, interpret and present their data internally and at appropriate conferences. This project will provide a broad range of transferable skills with a unique insight into translational research.
Project reference number: 750
|Dr Teresa Lambe||Jenner Institute||Oxford University, Old Road Campus Research Building||GBRfirstname.lastname@example.org|
|Professor Sarah C Gilbert||Jenner Institute||Oxford University, Old Road Campus Research Building||GBRemail@example.com|
|Professor Adrian VS Hill||Jenner Institute||Oxford University, Old Road Campus Research Building||GBRfirstname.lastname@example.org|
BACKGROUND: The West African outbreak of Ebola virus disease that peaked in 2014 has caused more than 11,000 deaths. The development of an effective Ebola vaccine is a priority for control of a future outbreak. METHODS: In this phase 1 study, we administered a single dose of the chimpanzee adenovirus 3 (ChAd3) vaccine encoding the surface glycoprotein of Zaire ebolavirus (ZEBOV) to 60 healthy adult volunteers in Oxford, United Kingdom. The vaccine was administered in three dose levels--1×10(10) viral particles, 2.5×10(10) viral particles, and 5×10(10) viral particles--with 20 participants in each group. We then assessed the effect of adding a booster dose of a modified vaccinia Ankara (MVA) strain, encoding the same Ebola virus glycoprotein, in 30 of the 60 participants and evaluated a reduced prime-boost interval in another 16 participants. We also compared antibody responses to inactivated whole Ebola virus virions and neutralizing antibody activity with those observed in phase 1 studies of a recombinant vesicular stomatitis virus-based vaccine expressing a ZEBOV glycoprotein (rVSV-ZEBOV) to determine relative potency and assess durability. RESULTS: No safety concerns were identified at any of the dose levels studied. Four weeks after immunization with the ChAd3 vaccine, ZEBOV-specific antibody responses were similar to those induced by rVSV-ZEBOV vaccination, with a geometric mean titer of 752 and 921, respectively. ZEBOV neutralization activity was also similar with the two vaccines (geometric mean titer, 14.9 and 22.2, respectively). Boosting with the MVA vector increased virus-specific antibodies by a factor of 12 (geometric mean titer, 9007) and increased glycoprotein-specific CD8+ T cells by a factor of 5. Significant increases in neutralizing antibodies were seen after boosting in all 30 participants (geometric mean titer, 139; P<0.001). Virus-specific antibody responses in participants primed with ChAd3 remained positive 6 months after vaccination (geometric mean titer, 758) but were significantly higher in those who had received the MVA booster (geometric mean titer, 1750; P<0.001). CONCLUSIONS: The ChAd3 vaccine boosted with MVA elicited B-cell and T-cell immune responses to ZEBOV that were superior to those induced by the ChAd3 vaccine alone. (Funded by the Wellcome Trust and others; ClinicalTrials.gov number, NCT02240875.). Hide abstract
Blood sampling to assess production of antigen-specific antibodies after immunization is commonly performed, but it presents logistical difficulties for trials carried out during an infectious disease outbreak. In this study, we show that antibodies may be reliably detected in oral fluid collected in a minimally invasive manner without use of sharps. Clinical Trials Registration. NCT02240875. Hide abstract
The epidemic of Ebola virus disease has spread at an alarming rate despite containment efforts. As a result, unprecedented large-scale international response efforts have been made in an attempt to gain control of the outbreak and reduce transmission. Several international consortia have been formed in a remarkable worldwide collaborative effort to expedite trials of two candidate Ebola virus vaccines: cAd3-EBOZ and rVSV-EBOV. In parallel, both vaccines are being manufactured in large amounts to enable future rapid deployment for management of the crisis. Hide abstract