An Unconventionally MHC-Restricted T Cell Vaccine for Influenza

Jonah Sacha of the Oregon Health & Science University in the U.S. will explore a new approach to vaccine design by using a cytomegalovirus (CMV) vector expressing conserved influenza antigens to induce an effector memory T cell response that persists in the lungs and can provide lifelong immunity against influenza. The development of a universal influenza vaccine is a top global health priority: four pandemic outbreaks in the last 100 years killed tens of millions of people, and current antibody-mediated vaccines target highly variable antigenic proteins that are extremely strain-specific and unable to protect against future threats. Work on HIV and tuberculosis vaccines has shown that CMV-vectored vaccines can elicit and maintain effector memory T cells (T_EM) at high frequency in the lung. While T_EM don’t protect against infection, they restrict pathogen replication in the lung to the point that it is effectively eliminated. They will extend this work to influenza vaccine development, determining whether a CMV vaccine can protect cynomolgus macaque monkeys from the highly pathogenic 1918 influenza strain. After establishing the minimum lethal dose of the virus, they will vaccinate monkeys with a CMV vector expressing three highly conserved influenza viral proteins. They will characterize the subsequent cellular immune response, and then challenge the vaccinated animals with a low dose of 1918 influenza to evaluate the ability of the vaccine to protect them from infection.