Exploring the Effects of Adjuvant Selection on a Novel Polyvalent Staphylococcus aureus Vaccine

Staphylococcus aureus is an important human pathogen that causes a wide range of morbidities, from superficial skin infections to severe and potentially lethal conditions like sepsis. The emergence of multi-drug-resistant strains and the subsequent reduction in effective antibiotic options underscore the necessity for alternative treatments, such as vaccines. This project explored the optimisation of a novel polyvalent S. aureus protein vaccine based on three highly conserved proteins from the staphylococcal superantigen-like (SSL) family: SSL3, SSL7 and SSL11. These proteins are immune evasion factors and target different aspects of the host's immune response. The novel vaccine candidate, polySSL, was expressed as a single fusion protein, and the efficacy was evaluated using an intraperitoneal murine infection model. Alternative orders for the polySSL were investigated, but a particular focus was on optimal adjuvant selection for enhanced immunogenicity. Immunisation with the polySSL in any order combined with the adjuvant AddaVax resulted in the production of antigen-specific IgG titres against each vaccine component with some neutralising capability and a reduction in S. aureus burden. Minor variations were observed between protein orders, but significant differences were observed in a pilot study exploring the addition of different pattern recognition receptor agonists combined with the adjuvant AdjuPhos. The addition of toll-like receptor 2 (TLR2)-containing agonists enhanced S. aureus clearance, and consequently, further cellular studies were undertaken with a novel TLR2 agonist to identify the protective host response. The splenocyte supernatant of mice immunised with the polySSL-TLR2 combination had increased production of the cytokines IFN-γ, TNF, and IL-6 following antigen-specific stimulation. Following S. aureus challenge, polySSL-vaccinated mice had higher proportions of CD4+ effector memory T cells. The use of the TLR2 agonist as a mucosal pretreatment for S. aureus was also evaluated using a murine colonisation model, which produced a localised inflammatory response with increased TNF and IL-1α but was ineffective at bacterial clearance. These results demonstrated the importance of adjuvant selection, and some insight was gained into desirable immune profiles. TLR2 agonists were highlighted as drivers of a protective S. aureus response when combined with the polySSL vaccine candidate. This promising S. aureus vaccine candidate warrants further investigation.

Name thesis:degree_name

PhD

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Biomedical Science

Grantor dc:publisher

ResearchSpace@Auckland

Year dc:date.issued

2025

Author dc:creator

• Peterken, Kelly Pania

Advisors dc:contributor.advisor

• Radcliff, Fiona
• Fraser, John

• vaccine
• adjuvant
• staphylococcus
• aureus

Statement dc:rights

• Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Licence dc:rights.uri

• https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm

Handle dc:identifier.uri

https://hdl.handle.net/2292/73549

OAI identifier oai:identifier

oai:researchspace.auckland.ac.nz:2292/73549