Full chemical synthesis of virus replicas by Osaka University and Tottori University group: Effective cancer vaccine candidate

A research group led by Graduate Student Keita Ito, Assistant Professor Yoshiyuki Manabe, and Professor Koichi Fukase of the Graduate School of Science at Osaka University, and another research group led by Graduate Student Hiroto Furukawa and Professor Kazunori Matsuura of the Graduate School of Engineering at Tottori University prepared envelope virus replicas loaded with cancer antigens and adjuvants (immunostimulants) and have found them to be promising cancer vaccine candidates. Their findings demonstrate that vaccines can be precisely designed using a completely chemical synthesis process, opening the way for new vaccine development. This outcome has been published in the Journal of the American Chemical Society.

Previously, Matsuura and his group had synthesized artificial virus-like particles by accumulating peptides that form the viral backbone. They also constructed envelope virus replicas by covering the virus-like particles with a lipid membrane. This envelope virus replica is a highly flexible nanomaterial whose physical properties (size, stability, charge) can be freely controlled, allowing it to carry a variety of molecules.

In this study, the researchers synthesized a β-annulus peptide conjugated with the breast cancer antigen CH401 and allowed it to self-assemble into a virus-like structure covered with positively charged lipids. During this process, the adjuvant α-galactosylceramide (α-GalCer) was mixed into the lipid component, allowing it to be loaded onto the envelope membrane.

The resulting virus replicas were aggregates of approximately 100 nanometers in size, which is considered desirable for a vaccine material. Envelope formation was confirmed by the presence of a lipid bilayer and the presentation of the CH401 peptide on the particle surface. When this envelope virus replica was administered to mice, it strongly induced the production of CH401-recognizing antibodies. Additionally, the resultant antibodies recognized breast cancer cells, indicating that the replica functioned as an effective vaccine.

Fukase stated, "After the experience with the COVID-19 pandemic, we have learned once again the importance of vaccine development. The immune system is extremely complex, and vaccine development is still in its infancy. By conducting basic research with a view toward application, we at the university are striving for technological innovation in this field."

Journal Information
Publication: Journal of the American Chemical Society
Title: Antigen/Adjuvant-Displaying Enveloped Viral Replica as a Self-Adjuvanting Anti-Breast-Cancer Vaccine Candidate
DOI: 10.1021/jacs.3c02679