Improved conjugate vaccines derived from a bacterial immunomodulatory protein
Lead Research Organisation:
University of Bath
Department Name: Biology and Biochemistry
Abstract
TB remains a major health and economic burden. Key discoveries (University of Bath) and initial vaccination studies (Newcastle University) have established that a bacterial protein known as Sbi (from Staphylococcus aureus) can improve immune responses to a TB fragment. What makes our Sbi pro-vaccines an attractive commercial opportunity is our findings that Sbi can locally activate the innate immune system of all mammals tested to date. As such, vaccines developed using Sbi could be used across multiple species, including cattle and humans.
Here, we will establish how successful Sbi conjugates/compounds are at generating an appropriate adaptive immune response against TB. These studies will lead to full TB challenge experiments in the future, which will allow us to confirm Sbi conjugates as highly effective multifunctional vaccines for animals; providing a clear pathway to commercialization of novel Sbi conjugate based vaccines to improve animal health and world food security.
Here, we will establish how successful Sbi conjugates/compounds are at generating an appropriate adaptive immune response against TB. These studies will lead to full TB challenge experiments in the future, which will allow us to confirm Sbi conjugates as highly effective multifunctional vaccines for animals; providing a clear pathway to commercialization of novel Sbi conjugate based vaccines to improve animal health and world food security.
Publications
Yang Y
(2018)
Utilization of Staphylococcal Immune Evasion Protein Sbi as a Novel Vaccine Adjuvant.
in Frontiers in immunology
Wahid AA
(2019)
Ensilication Improves the Thermal Stability of the Tuberculosis Antigen Ag85b and an Sbi-Ag85b Vaccine Conjugate.
in Scientific reports
Wahid AA
(2021)
Insights Into the Structure-Function Relationships of Dimeric C3d Fragments.
in Frontiers in immunology
Dunphy RW
(2022)
Staphylococcal Complement Evasion Protein Sbi Stabilises C3d Dimers by Inducing an N-Terminal Helix Swap.
in Frontiers in immunology
Doekhie A
(2020)
Ensilicated tetanus antigen retains immunogenicity: in vivo study and time-resolved SAXS characterization.
in Scientific reports
Doekhie A
(2020)
Thermal resilience of ensilicated lysozyme via calorimetric and in vivo analysis.
in RSC advances
Description | This award has helped to generate insight in how to utilise activation of human innate immune system to improve vaccines. We have shown this with antigen that has potential as a novel tuberculosis vaccine and we have shown that activation of a specific part of the innate immune system, the complement system, aids in the recognition of the antigen by the immune system resulting in increased antobody production specific for the antigen. In addition we have been able to show develop ways of making the antigen more thermostable. We are now in the process in applying our findings to improve other disease antigens. |
Exploitation Route | We aim to apply our technology to improve other vaccines and have started a collaboration with the company Porton Biopharma Ltd to improve their antrax vaccine. They are currently funding a joint PhD studentship to further develop our technology. |
Sectors | Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
URL | https://www.bath.ac.uk/announcements/thermally-stable-tb-vaccine-closer-to-reality-thanks-to-microscopic-silica-cages/ |
Description | The award of this grant was publicised on the University of Bath web site and this news item generated public interest and resulted in coverage on national radio and television. Coverage includes radio interviews on Radio4 (Farming Today) and BBC Bristol, and TV appearances on BBC Country File and BBC Points West. I also presented a talk on the topic of the grant during a public lecture at the University of Bath (Minerva lecture). Based on the research outcomes of this grant the University of Bath filed a patent application for the use of Sbi as an adjuvant to improve vaccines: WO Application No: PCT/EP2017/080321 "Immunogenic compositions comprising Sbi protein and uses thereof". |
First Year Of Impact | 2014 |
Impact Types | Societal |
Title | Improved vaccine conjugates |
Description | We have developed a new adjuvant based on Staphylococcus aureus immune evasion protein Sbi and created a vaccine conjugate for TB. The University of Bath has filed a patent application for this technology and we aim to further develop this as platform technology for improved vaccines to prevent a range of infectious disease in animal and human hosts. |
Type Of Material | Technology assay or reagent |
Year Produced | 2017 |
Provided To Others? | No |
Impact | we aim to further develop this as platform technology for improved vaccines to prevent a range of infectious disease in animal and human hosts. |
Title | Dataset for "Ensilicated tetanus antigen retains immunogenicity: in vivo study and time-resolved SAXS characterization" |
Description | This dataset contains the SAXS data obtained at i22 (Diamond Light Source) and ID02 beamline (ESRF). Other data such as ELISA and Circular Dichroism are also included. All data is organised by figures presented in the research paper. Majority of data is stored in excel or csv format with processing done in MatLab for graphical presentation. |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
URL | https://researchdata.bath.ac.uk/id/eprint/771 |
Title | Dataset for "Thermal resilience of ensilicated lysozyme via calorimetric and in vivo analysis" |
Description | This dataset contains a variety of data formats used to characterise the thermal resilience of ensilicated lysozyme. All raw data formats have been converted to *.csv or similar Excel format, which is editable. MATLAB is used to generate all graphs and files have been included in each folder where applicable. Specifically, data were generated using analytical methods such a differential scanning calorimetry, circular dichroism spectroscopy, enzyme-linked immunosorbent assay (ELISA) and thermogravimetric analysis. Data is sorted based on the figure order described in the article, including supplementary figures. Each folder contains a brief explanation on the contents. |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
URL | https://researchdata.bath.ac.uk/id/eprint/895 |
Description | Co-applicant |
Organisation | Newcastle University |
Department | Institute of Cellular Medicine |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Dr Kevin Marchbank is a co-applicant on this grant |
Collaborator Contribution | Dr Marchbank contributes to the in vivo studies in this research project |
Impact | This is a multi-disciplinary collaboration which has resulted in joint publication and a patent application |
Start Year | 2014 |
Description | Minerva lecture |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | Public lecture organised by the University of Bath to engage with the general public in the Bath area |
Year(s) Of Engagement Activity | 2016 |
URL | https://soundcloud.com/uniofbath/sets/minerva-series |
Description | Public lecture Royal Society of Biology |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | This is a public lecture organised by the Royal Society of Biology local branch (Bristol/Bath) |
Year(s) Of Engagement Activity | 2018 |
URL | https://my.rsb.org.uk/item.php?eventid=2231 |