Science Bite (3 minute oral presentation with PPT in live session and poster) - Students and ECRs only Lorne Infection and Immunity 2023

A novel recombinant Lactococcus lactis mucosal vaccine platform based on group A streptococcus pili (#57)

Catherine Tsai 1 2 , Sam Blanchett 3 , Jacelyn Loh 1 2 , Kohtaro Fijihashi 4 , Thomas Proft 1 2
  1. Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand
  2. Maurice Wilkins Centre, University of Auckland, Auckland, New Zealand
  3. Division of Infection & Immunity, Faculty of Medical Sciences, University College London, London, United Kingdom
  4. Institute of Medical Science, University of Tokyo, Tokyo, Japan

Well-defined synthetic peptides are attractive for vaccine development. However, they are usually poorly immunogenic and sensitive to proteolytic degradation, thus require conjugation to carrier proteins and/or addition of adjuvants. Lactic acid bacteria (LAB) have become promising vehicle for mucosal vaccines due to their safety profile and natural adjuvanticity. The choice of carrier and mode of presentation hugely affect the stability and immunogenicity of the antigen, thus determine effectiveness of the resulting vaccines. We propose that the group A streptococcus (GAS) pilus structure expressed on the surface of Lactococcus lactis can be an ideal carrier for antigenic peptides, and established a novel mucosal vaccine platform termed PilVax1. Pili (sing. pilus) are hair-like bacterial cell surface protrusions important for host cell adhesion. The GAS pili consist of covalently linked pilins that are structurally stable and highly immunogenic. We identified several regions within the backbone pilin that can be replaced with antigenic peptides. Expressing the peptides within the pilus structure allows for peptide amplification, stabilisation and enhanced immunogenicity. Intranasal immunisation of mice with the resulting recombinant L. lactis strain produced strong peptide-specific antibody responses in serum and bronchoalveolar fluid. A recently developed tuberculosis vaccine based on a dominant T-cell epitope generated both humoral and cellular immune responses in the immunised mice2. PilVax vaccination resulted in peptide-specific CD4+ T cells at levels similar to those resulting from BCG immunisation, as well as an unexpected increase in the numbers of CD3+CD4-CD8- (double negative [DN]) T cells in the lungs of vaccinated animals. These cells types were shown to be responsible for the cytokine production following stimulation with the cognate peptide. This presentation will also give an overview of other PilVax projects focusing on various infectious diseases, including gonorrhoea and influenza. Results from these ongoing studies demonstrate the suitability of developing PilVax into useful mucosal vaccines.

  1. Wagachchi D, Tsai JC, Chalmers C, Blanchett S, Loh JMS, Proft T. PilVax - a novel peptide delivery platform for the development of mucosal vaccines. Sci Rep. 2018;8(1):2555.
  2. Blanchett S, Tsai CJ, Sandford S, Loh JM, Huang L, Kirman JR, et al. Intranasal immunization with Ag85B peptide 25 displayed on Lactococcus lactis using the PilVax platform induces antigen-specific B- and T-cell responses. Immunol Cell Biol. 2021.