October, 2023
Abstract
The measles vaccine (MV) delivery platform has undergone development from preclinical to clinical stages, demonstrating its ability to adapt rapidly and effectively to different pathogens. The live pediatric MV holds extensive history of safety and efficacy, along with its established large-scale manufacturing capacity. To further enhance the capabilities of MV vector, we have engineered an improved MV vector using a bacterial artificial chromosome (BAC) plasmid. With the stability of BAC plasmids, this new MV vector can now accommodate and maintain the expression of more than 7 kb of additional heterologous gene/s within a single rescued recombinant MV. Moreover, the incorporation of additional transcription unit sites enables the insertion of multiple additional genes in tandem into measles sequence. Our proof-of-concept demonstrated the successful construction of a combined MV vector that expresses three protective antigens derived from the Chikungunya virus (CHIKV), West Nile virus (WNV), and Zika virus (ZIKV), simultaneously. Immunization of mice with this replication-competent multivalent vaccine elicited robust immunogenicity to all three viruses, both humoral and cell-mediated immune responses, and conferred effective protection from individual challenges.
Phanramphoei N. Frantz (Institut Pasteur, Université Paris Cité, Innovation Lab: Vaccines, Paris, France, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency, Virology and Cell Technology Laboratory, Pathumthani, Thailand, Oncovita, Paris, France)
Claude Ruffie (Institut Pasteur, Université Paris Cité, Innovation Lab: Vaccines, Paris, France),
Chantal Combredet (Institut Pasteur, Université Paris Cité, Innovation Lab: Vaccines, Paris, France),
Valérie Najburg (Institut Pasteur, Université Paris Cité, Innovation Lab: Vaccines, Paris, France),
Eddy Simard (Institut Pasteur, Université Paris Cité, Innovation Lab: Vaccines, Paris, France),
Frédéric Tangy (Institut Pasteur, Université Paris Cité, Innovation Lab: Vaccines, Paris, France, Oncovita, Paris, France)
Institut Pasteur, Université Paris Cité, Innovation Lab: Vaccines, Paris, France
National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency, Virology and Cell Technology Laboratory, Pathumthani, Thailand
Oncovita, Paris, France
