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A Complex Dance: Measuring the Multidimensional Worlds of Influenza Virus Evolution and Anti-Influenza Immune Responses

1
Department of Medicine, Division of Nephrology, University of Rochester Medical Center, Rochester, NY 14534, USA
2
Clinical and Translational Science Institute, University of Rochester Medical Center, Rochester, NY 14534, USA
*
Author to whom correspondence should be addressed.
Pathogens 2019, 8(4), 238; https://doi.org/10.3390/pathogens8040238
Received: 25 September 2019 / Revised: 29 October 2019 / Accepted: 12 November 2019 / Published: 15 November 2019
(This article belongs to the Special Issue Influenza Virus and Vaccination)
The human antibody response to influenza virus infection or vaccination is as complicated as it is essential for protection against flu. The constant antigenic changes of the virus to escape human herd immunity hinder the yearly selection of vaccine strains since it is hard to predict which virus strains will circulate for the coming flu season. A “universal” influenza vaccine that could induce broad cross-influenza subtype protection would help to address this issue. However, the human antibody response is intricate and often obscure, with factors such as antigenic seniority or original antigenic sin (OAS), and back-boosting ensuring that each person mounts a unique immune response to infection or vaccination with any new influenza virus strain. Notably, the effects of existing antibodies on cross-protective immunity after repeated vaccinations are unclear. More research is needed to characterize the mechanisms at play, but traditional assays such as hemagglutinin inhibition (HAI) and microneutralization (MN) are excessively limited in scope and too resource-intensive to effectively meet this challenge. In the past ten years, new multiple dimensional assays (MDAs) have been developed to help overcome these problems by simultaneously measuring antibodies against a large panel of influenza hemagglutinin (HA) proteins with a minimal amount of sample in a high throughput way. MDAs will likely be a powerful tool for accelerating the study of the humoral immune response to influenza vaccination and the development of a universal influenza vaccine. View Full-Text
Keywords: influenza virus; humoral response; hemagglutinin (HA) of influenza virus; broad neutralizing antibody(bnAb); heterosubtypic immunity of influenza; original antigenic sin “OAS”; “universal” influenza vaccine; protein microarray assay; mPLEX-Flu assay; multiple dimensional assay (MDA) influenza virus; humoral response; hemagglutinin (HA) of influenza virus; broad neutralizing antibody(bnAb); heterosubtypic immunity of influenza; original antigenic sin “OAS”; “universal” influenza vaccine; protein microarray assay; mPLEX-Flu assay; multiple dimensional assay (MDA)
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Wang, J.; Wiltse, A.; Zand, M.S. A Complex Dance: Measuring the Multidimensional Worlds of Influenza Virus Evolution and Anti-Influenza Immune Responses. Pathogens 2019, 8, 238.

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