MCMV-based vaccine vectors expressing full-length viral proteins provide long-term humoral immune protection upon a single-shot vaccination

摘要

Global pandemics caused by influenza or coronaviruses cause severe disruptions to public health and lead to high morbidity and mortality.There remains a medical need for vaccines against these pathogens.CMV(cytomegalovirus)is aβ-herpesvirus that induces uniquely robust immune responses in which remarkably large populations of antigen-specific CD8+T cells are maintained for a lifetime.Hence,CMV has been proposed and investigated as a novel vaccine vector for expressing antigenic peptides or proteins to elicit protective cellular immune responses against numerous pathogens.We generated two recombinant murine CMV(MCMV)vaccine vectors expressing hemagglutinin(HA)of influenza A virus(MCMV^(HA))or the spike protein of severe acute respiratory syndrome coronavirus 2(MCMV^(S)).A single injection of MCMVs expressing either viral protein induced potent neutralizing antibody responses,which strengthened over time.Importantly,MCMV^(HA)-vaccinated mice were protected from illness following challenge with the influenza virus,and we excluded that this protection was due to the effects of memory T cells.Conclusively,we show here that MCMV vectors induce not only long-term cellular immunity but also humoral responses that provide long-term immune protection against clinically relevant respiratory pathogens.