CE17 - Recherche translationnelle en santé

Combo vaccines for emerging infectious diseases – ComboVaxEm

Combovax

To develop combined vaccines against several emerging infectious diseases using the measles vector vaccine platform developed in the laboratory and clinically validated.

To develop combined vaccines against several arbovirosis

Several arboviruses, such as dengue fever, Zika fever, chikungunya, or West Nile virus circulate simultaneously in the same geographical areas. It would be interesting to have multivalent vaccines against several of these infections which can be fatal.

To carry out this work, we had to develop a new measles vector with the capacity to incorporate very large additional inserts. Indeed, a trivalent vaccine against CHIKV, ZIKV and WNV requires the incorporation of more than 7.5 kb of additional genetic material into the measles viral genome of 16 kb. We have therefore developed a new vector based on a bacterial artificial chromosome expressing the complete genome of the measles virus in which large additional sequences can be cloned.

This new vector has been constructed. It makes it possible to reconstitute by reverse genetics the measles vaccine virus containing large additional inserts. All the recombinant vectors expressing two or three of the antigens of this program have been produced and characterized.

These new vaccine candidates will soon be tested for their immunogenicity and their protective efficacy in mice models that we have already established. Then the best candidate will be evaluated in the primate with our partner IDMIT.

An international patent EP20305789 was filed on July 8, 2020 to protect the new vaccine platform developed.
A scientific article corresponding to this patent is in the process of being finalized.

Infectious disease epidemics match wars and natural disasters in their capacity to endanger lives, disrupt societies and damage economies. Like SARS previously and Zika recently, the Ebola crisis in 2015 showed how vulnerable the world is to epidemics of infectious diseases. Many of these epidemic diseases could be prevented with vaccines but very few vaccines against these threats have been developed so far. The objective of this project is to pre-clinically evaluate the immunogenicity in non-human primates (NHP) of a single ComboVax vaccine designed to prevent simultaneously several deadly emergent infectious diseases: WNV, CHIKV, and ZIKV. The proposed combo vaccine is based on the measles vaccine vector (MV) platform previously developed by Institut Pasteur, which allows rapid and cost effective vaccine delivery in response to epidemic threats with demonstrated proof of principle in humans and a preclinical track record of rapid adaptability and effectiveness for a variety of pathogens. Based on the very efficient protective capacity of three previously developed individual vaccine candidates (MV-WNV, MV-CHIKV, MV-ZIKV), we will generate a single combined MV vaccine expressing simultaneously the same three protective antigens (ComboVax). We will evaluate the immunogenicity and protective efficacy of this new candidate in mice and NHP in comparison to a mixture of the individual vaccines. This study should pave the way for evaluating more complex combinations to prevent several emerging diseases with strong geographic circulation overlap.

Project coordination

Frédéric Tangy (INSTITUT PASTEUR)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

IDMIT Département lnfectious Disease Models and lnnovative Therapies
G2V INSTITUT PASTEUR

Help of the ANR 648,920 euros
Beginning and duration of the scientific project: - 36 Months

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