Group A Streptococcus (GAS) is a major global pathogen which causes a range of infections from mild pharyngitis to severe necrotising fasciitis, as well as autoimmune conditions such as rheumatic heart disease (RHD).
Annually there are over 600 million cases of pharyngitis and approximately 33 million cases of RHD the latter leading to a conservative estimate of 300,000 deaths globally. This places GAS among the top 10 causes of infectious disease mortality.
Due to this high burden of disease, the World Health Organization (WHO) have highlighted the unmet global health need for a vaccine against GAS. Several targets are in pre-clinical or clinical trials and focus on the major virulence factor of GAS, the M protein, which is a highly variable surface protein, or alternative conserved antigens in multicomponent vaccines.
Little is known of the correlates of protection or the role of mucosal immunity in preventing GAS infections. We are interested in understanding more deeply the immune response to GAS infection and immunisation, particularly at mucosal sites.
We have active collaborations with The London School of Hygiene and Tropical Medicine (LSHTM), Dundee University, Sheffield University and GlaxoSmithKline (GSK). If you are interested in collaborating with us on a project or are a student with funding and interested in a placement with us, please get in touch.
We are developing and optimising in vitro assays for assessing functional immunity from immunisation with GAS antigens to complement our research focuses and prepare for future vaccines.
Established assays within our group include an opsonophagocytosis assay, pharyngeal cell binding, extracellular matrix binding, ELISA, IL-8 cleavage and IgG cleavage. We are also establishing assays to test glycoconjugate vaccines such as polysaccharide and carrier protein identity tests, total and free polysaccharide content and molecular size.
The majority of vaccines under investigation focus on the main virulence factor of GAS, the M protein. This protein has high sequence variation, requiring inclusion of multiple serotypes in vaccine formulations. Some vaccines have targeted the conserved domain of this protein, but protection is less effective than against the variable region. Consequently, there is interest in investigating other conserved or important virulence factors as vaccine targets.
Due to sequence variation, differential gene presence and expression, and a variety of infection presentations, targeting single proteins is complicated. It is therefore necessary to consider multicomponent vaccines with broad strain and disease coverage.
We are investigating a panel of protein antigens as a multicomponent vaccine, and are evaluating the protective, neutralising and colonisation inhibiting effects of antibodies induced from immunisation. Our focus is primarily on whether targeting multiple facets of GAS infections can improve protection without compromising the effective response to individual components.
We have a PhD project investigating production of a glycoconjugate vaccine against GAS in collaboration with LSHTM. The project is focusing on the use of chemical and novel biological conjugation methodologies for producing a “double-hit” glycoconjugate vaccine containing the Group A Carbohydrate and GAS specific protein antigens.
We are interested in whether this “double-hit” approach will enhance vaccine efficacy without compromising protective epitopes. If a novel biological approach is possible and effective this could lead the way to cheaper and simpler production for a global vaccine.
Recombinant vaccines are a useful tool to ensure vaccine safety but often produce a weak immune response compared with whole cell vaccines. We are interested in whether incorporating vaccine antigens into “cell-like” structures could enhance the protective immune response against GAS. Towards this we have an active collaboration with GSK using their Generalised Modules for Membrane Antigens (GMMA) platform and are investigating Multiple Antigen Presenting Systems (MAPS) as a technology for a novel “cell-like” glycoconjugate.
The WHO have highlighted prevention of pharyngitis as the ideal measure for an effective vaccine. Despite this, the mucosal immune response to GAS infections in the pharynx, as well as other mucosal sites, is still poorly understood. To ensure an effective vaccine which can target GAS at mucosal colonisation and infection sites a better understanding of the immune response to GAS and immunisation is needed.
Together with the University of Sheffield we are investigating the antibody response to GAS antigens in human saliva and blood samples. We are also researching the immune response generated by immunisation at mucosal sites compared with injection to determine the optimal route to induce protective immunity generation.
Fatme Mawas – Principal ScientistAlexandra Shaw – Senior ScientistJames Ozanne – ScientistKeira Burns – PhD Student