Recalling the Future: Immunological Memory Toward Unpredictable Influenza Viruses

Abstract

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.

Fueling influenza and the immune response: Implications for metabolic reprogramming during influenza infection and immunometabolism

“…Moreover, Th are necessary for the development of effective IAV-specific Tm. [283][284][285] An emerging consensus arising from studies on T cell immunometabolism indicates the metabolic utilization of glucose and glutamine, as opposed to FAO, may have implications in quiescence versus activation of T cells. 265 CD4 T cell help during priming is essential for promoting metabolic programs that enhance respiratory capacity and glycolysis, and these enhancements drive better recall responses necessary for IAV-specific Tm development.…”

<p>Immunoinformatics and Vaccine Development: An Overview</p>

“…T cell responses to viral pathogens differ from one patient to the other, basically because of the expression of differing HLA (MHC) alleles which determine the several viral amino acid sequence brought to the T cells to read. 136,137 It is most likely that during an infection, diverse epitopes are usually presented to the T cells to read owing to the several forms of HLA alleles and also because each human person expresses six HLA Class I and six HLA Class II alleles. 138 Now, antibody-binding sites in a given HLA (MHC) molecule are mostly prediction-servers predetermined on the basis of particular binding motifs and the anchor residues.…”

Epigraph Hemagglutinin Vaccine Induces Broad Cross-reactive Immunity Against Swine H3 Influenza Virus

“…long-lasting immunity against influenza virus [40][41][42][43] . In contrast, the role of T cells during influenza infection in swine has not been as well defined.…”