Periodic Reporting for period 1 - VacCan (Development of new multi-valent vaccine systems against Candida pathogens)
Okres sprawozdawczy: 2021-07-01 do 2023-06-30
Fungal infections kill an estimated 1.5 million people each year, four times greater than the global mortality due to malaria or breast cancer. The fungal pathogen Candida albicans is the most pathogenic of the Candida species and causes millions of superficial mucosal infections and approximately 200,000 deaths per annum due to invasive and disseminated disease in susceptible patient populations. Fungal infections in immunocompromised patients have an unacceptably high mortality rate of approximately 40%, and the yearly healthcare expenditure for the treatment of fungal diseases is estimated to be $15 billion. The clinical treatment of fungal diseases is hampered by poor and time-consuming diagnostics, a limited repertoire of anti-fungal drugs, and increasing levels of resistance to anti-fungal prophylaxis. Crucially, there are currently no licensed vaccines against fungal pathogen. This represents a clear opportunity in global healthcare provision. The principal objective of this project was developing a new vaccine candidate to Candida albicans, the leading cause of fungal infection in humans worldwide.
Work performed: Purification of proteins.
Main results achieved:
a) Expression, purification, and characterisation of Als3 protein (316 amino acids) from Escherichia coli.
Work performed: Formulation of liposome as a vaccine candidate.
Main results achieved:
a) Chemical, and site-specific modification of proteins from C. albicans (Als3, Sap2 and Clys).
b) Protocol for the formulation of a liposome-conjugated vaccine candidate containing modified proteins (Als3, Sap2 and Clys) from C. albicans.
Work performed: Evaluation of the in vivo efficacy of the vaccine candidates.
Main results achieved:
a) The evaluation of the liposome-conjugate formulation (first batch) containing alum as adjuvant was performed in vivo using an established murine model of systemic candidiasis. Mice were immunised at week 2 and week 4 via intramuscular administration.
b) The evaluation of the liposome-conjugate formulation (second batch) containing CAF01 as adjuvant was performed in vivo using an established murine model of systemic candidiasis. Mice were immunised at week 2 and week 4 via intramuscular administration.
Work performed: Exploitation and dissemination of results.
Main results achieved:
a) Oral presentation in the Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King´s College London, 3 July 2023. “Multicomponent protein vaccine against C. albicans”.
b) Oral presentation at the King´s College London Soft Matter Meeting, 21 February 2023. “Multicomponent protein vaccine against C. albicans”.
c) Oral presentation in the Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King´s College London, 18 July 2022. “Design and synthesis of a multicomponent protein system”.
Main results achieved:
a) Expression, purification, and characterisation of Als3 protein (316 amino acids) from Escherichia coli.
Work performed: Formulation of liposome as a vaccine candidate.
Main results achieved:
a) Chemical, and site-specific modification of proteins from C. albicans (Als3, Sap2 and Clys).
b) Protocol for the formulation of a liposome-conjugated vaccine candidate containing modified proteins (Als3, Sap2 and Clys) from C. albicans.
Work performed: Evaluation of the in vivo efficacy of the vaccine candidates.
Main results achieved:
a) The evaluation of the liposome-conjugate formulation (first batch) containing alum as adjuvant was performed in vivo using an established murine model of systemic candidiasis. Mice were immunised at week 2 and week 4 via intramuscular administration.
b) The evaluation of the liposome-conjugate formulation (second batch) containing CAF01 as adjuvant was performed in vivo using an established murine model of systemic candidiasis. Mice were immunised at week 2 and week 4 via intramuscular administration.
Work performed: Exploitation and dissemination of results.
Main results achieved:
a) Oral presentation in the Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King´s College London, 3 July 2023. “Multicomponent protein vaccine against C. albicans”.
b) Oral presentation at the King´s College London Soft Matter Meeting, 21 February 2023. “Multicomponent protein vaccine against C. albicans”.
c) Oral presentation in the Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King´s College London, 18 July 2022. “Design and synthesis of a multicomponent protein system”.
The lack of a clinically approved vaccine against life-threatening C. albicans infections is of major concern. While current sub-optimal vaccine candidates have focussed on individual C. albicans proteins and adjuvants, this project has developed a new vaccine formulation for the simultaneous delivery of Als3p, Sap2p and candidalysin to promote immune responses against C. albicans. This strategy ensures the concurrent delivery of multiple antigens and selected adjuvants to the immune system, which more closely represents the situation encountered by the human body during a real pathogenic encounter. The main outcome of this project was to provide clear deliverables towards effective therapeutic intervention against systemic candidiasis. The impact of this work includes interest from the pharmaceutical industry with the specific remit of targeting "at-risk" individuals to combat systemic (and potentially mucosal) C. albicans infection through innovative EU-based vaccine research.