Emergex and Bio-Manguinhos/Fiocruz Elucidate T Cell Epitopes Produced by Commercial Yellow Fever Vaccine

·         First identification of epitopes which shape CD8 T cell response to commercial live attenuated vaccine has implications across RNA virus vaccine development

·         Vaccine primes immune system against T cell epitopes that would be minor or subdominant in a natural infection and are derived from internal proteins

Abingdon, UK and Rio de Janeiro, Brazil, 19 August 2020  – Emergex Vaccines Holding Limited (‘Emergex’), a company tackling major global infectious disease threats through the development of synthetic ‘set point’ vaccines which prime the T cell immune response, and researchers at the Institute of Technology on Immunobiologicals of the Oswaldo Cruz Foundation (Bio-Manguinhos/Fiocruz), today announce the determination of the MHC CD8 T cell epitope expression library for Fiocruz’s commercial yellow fever vaccine on six major HLA supertypes.

This epitope library, which is expressed on Class I molecules of cells infected with the vaccine virus, shapes the CD8 T cell repertoire that will generate immunity to future exposure to wild type yellow fever virus.

The results unexpectedly showed that despite the high molar abundance of the surface E glycoprotein, no T cell epitopes are derived from the E protein of yellow fever vaccine virus. All epitopes ranging in peptide size of 8 - 15aa were derived from internal proteins. This result contrasts with Emergex determined CD8 T cell expression libraries for wild type Dengue and Zika viruses in which epitopes from the analogous E proteins were found.

These results represent a first analysis of T cell epitopes produced by a live attenuated commercial vaccine and provide new insight into the mechanism of action of such vaccines. The results also have implications for the current development of COVID-19 vaccines that rely on a clinically relevant CD8 T cell response to epitopes derived from the spike glycoprotein.

Professor Thomas Rademacher, CEO and co-founder of Emergex, commented: “Live attenuated viral vaccines are universally recognized as the only vaccines produced to date that can safely control RNA viral infections. However, vaccines such as yellow fever, measles, and polio were all empirically developed by multiple passage in cell lines with the original yellow fever vaccine dating back to 1926. Recent deep sequencing studies of quasi species diversity of yellow fever and polio vaccines suggest a limit repertoire of variants compared to wild type viruses. These new results now suggest the mechanism by which these low bottleneck vaccines can generate long-term immunity without causing disease, highlighting the critical role of epitopes derived from internal viral proteins in generating a safe, effective and long-lived response. This has important implications for the development of RNA vaccines more widely, including those being developed for COVID-19.”