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

Aug. 19, 2020 06:00 UTC

• 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, England & RIO DE JANEIRO--(BUSINESS WIRE)-- 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.”

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About Emergex

Emergex, a UK-based biotechnology company headquartered in Abingdon, UK, is pioneering the development of synthetic ‘set point’ vaccines which prime the T cell immune response to address some of the world’s most immediate health threats such as Dengue Fever, Zika, Ebola, pandemic flu and serious intra-cellular bacterial infections.

These set-point vaccines modify the initial immune status of recipients in a way that ‘primes’ their immune systems to recognise subsequent infectious agents much like a natural infection would do, preventing an acute or severe manifestation of the disease.

Emergex combines validated technologies together with the very latest scientific insights to develop its vaccines, including using synthetic peptide codes determined on actual infected cells and using a proprietary gold nanoparticle carrier system for programming.

The Company has a growing pipeline of vaccine candidates. The most advanced development programme is a vaccine for Dengue Fever, which may also be disease modifying for other Flaviviruses such as the Zika and Yellow Fever viruses. Emergex also has programmes in development for a universal Influenza vaccine and a universal Filovirus vaccine (including viruses such as Ebola and Marburg) and discovery programmes for a Yellow Fever Booster vaccine and a Chikungunya vaccine.

Emergex has partnered with the Institute of Molecular and Cell Biology (IMCB) of Singapore to develop a vaccine for the emerging threat of Hand, Foot and Mouth (HFM) disease and has signed a Memorandum of Understanding (MoU) with Brazil-based Oswaldo Cruz Foundation ‘Fiocruz’ for the development of viral vaccines. This initially covers the development of a vaccine that universally targets diseases within the flavivirus family such as Dengue Fever, Zika and Yellow Fever but could be expanded to include the development of vaccines to target other viral families that are endemic to the region.

Find out more online at www.emergexvaccines.com.

About Bio-Manguinhos/Fiocruz

As part of the Brazilian Ministry of Health, for 44 years the Institute of Technology on Immunobiologicals of the Oswaldo Cruz Foundation (Bio-Manguinhos/Fiocruz) has expanded access to health care for the population through the research, development and supply of products that prevent, diagnose and treat diseases. To establish itself as the largest public laboratory in Latin America, Bio-Manguinhos wrote parts of the History of Public Health in Brazil. It has played a decisive role in the eradication of poliomyelitis in the country and in the Americas; was instrumental in the control of measles and yellow fever, becoming one of the main producers of this vaccine in the world, having already exported to more than 70 countries.

Partnerships with public and private institutions through technology transfer agreements, Partnerships for Productive Development (PDPs) and autochthonous development projects contribute to the expansion of its portfolio, which has more than 40 products among vaccines, in vitro diagnostics (IVDs) and biopharmaceuticals. Each year, millions of units are provided to the Brazilian Ministry of Health programs.

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