Abstract
Understanding protective influenza immunity and identifying immune correlates of protection poses a major challenge and requires an appreciation of the immune system in all of its complexity. While adaptive immune responses such as neutralizing antibodies and influenza-specific T lymphocytes are contributing to the control of influenza virus, key factors of long-term protection are not well defined. Using systems immunology, an approach that combines experimental and computational methods, we can capture the systems-level state of protective immunity and reveal the essential pathways that are involved. New approaches and technological developments in systems immunology offer an opportunity to examine roles and interrelationships of clinical, biological, and genetic factors in the control of influenza infection and have the potential to lead to novel discoveries about influenza immunity that are essential for the development of more effective vaccines to prevent future pandemics. Here, we review recent developments in systems immunology that help to reveal key factors mediating protective immunity.
Highlights
Cross-species infectivity and antigenic shift caused by genetic reassortment, i.e., the process in which two different influenza virus strains swap their genes in a common animal reservoir, are causing the emergence of novel influenza strains that have pandemic potential [2,3,4,5]
The best-defined correlate of influenza immunity are antibodies directed against the hemagglutinin (HA), and a hemagglutinin inhibition (HI) titer ≥ 40 is associated with a 50% reduction in risk of influenza infection or illness [16]
We integrated immunological measurements acquired from 2007 to 2015 from 747 individuals analyzed at the Stanford University Human Immune Monitoring Center. This is a unique source in terms of value and scale that can be used to broaden our understanding of influenza immunity
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The development of high-throughput platforms, such as ‘systems serology’, is guiding the analysis of the functional properties of antigen-specific antibodies isolated from serum of vaccinated or infected humans [38] These new approaches and technological developments in systems biology allow examination of the roles and interrelationships of clinical, environmental, biological and genetic factors in the control of infectious diseases [30]. The power of the systems vaccinology approach was first demonstrated using the yellow fever live-attenuated vaccine [39,40] These initial proofof-concept studies revealed transcriptional signatures involved in antiviral sensing and viral immunity correlating with the magnitude of antigen-specific T cell and neutralizing antibody responses [39,40]. The main question on how pre-existing immunological determinants (i.e., immunological memory) can predict the outcome of antibody responses following vaccination has remained unanswered
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