[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]
Front Immunol. 2019 Jul 2;10:1400. doi: 10.3389/fimmu.2019.01400. eCollection 2019.
Recalling the Future: Immunological Memory Toward Unpredictable Influenza Viruses.
Auladell M1, Jia X1, Hensen L1, Chua B1,2, Fox A3, Nguyen THO1, Doherty PC1,4, Kedzierska K1.
Author information: 1 Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, Australia. 2 Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan. 3 WHO Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia. 4 Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN, United States.
Persistent and durable immunological memory forms the basis of any successful vaccination protocol. Generation of pre-existing memory B cell and T cell pools is thus the key for maintaining protective immunity to seasonal, pandemic and avian influenza viruses. Long-lived antibody secreting cells (ASCs) are responsible for maintaining antibody levels in peripheral blood. Generated with CD4+ T help after naïve B cell precursors encounter their cognate antigen, the linked processes of differentiation (including Ig class switching) and proliferation also give rise to memory B cells, which then can change rapidly to ASC status after subsequent influenza encounters. Given that influenza viruses evolve rapidly as a consequence of antibody-driven mutational change (antigenic drift), the current influenza vaccines need to be reformulated frequently and annual vaccination is recommended. Without that process of regular renewal, they provide little protection against “drifted” (particularly H3N2) variants and are mainly ineffective when a novel pandemic (2009 A/H1N1 “swine” flu) strain suddenly emerges. Such limitation of antibody-mediated protection might be circumvented, at least in part, by adding a novel vaccine component that promotes cross-reactive CD8+ T cells specific for conserved viral peptides, presented by widely distributed HLA types. Such “memory” cytotoxic T lymphocytes (CTLs) can rapidly be recalled to CTL effector status. Here, we review how B cells and follicular T cells are elicited following influenza vaccination and how they survive into a long-term memory. We describe how CD8+ CTL memory is established following influenza virus infection, and how a robust CTL recall response can lead to more rapid virus elimination by destroying virus-infected cells, and recovery. Exploiting long-term, cross-reactive CTL against the continuously evolving and unpredictable influenza viruses provides a possible mechanism for preventing a disastrous pandemic comparable to the 1918-1919 H1N1 “Spanish flu,” which killed more than 50 million people worldwide.
KEYWORDS: B cells; T cells; immunological memory; influenza; vaccine
PMID: 31312199 PMCID: PMC6614380 DOI: 10.3389/fimmu.2019.01400
Keywords: Influenza A; Seasonal Influenza; Pandemic Influenza; Vaccines; Immunology.