Journal
PATHOGENS
Volume 8, Issue 4, Pages -Publisher
MDPI
DOI: 10.3390/pathogens8040238
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)
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Funding
- National Institutes of Health Institute of Allergy, Immunology and Infectious Diseases [R01 AI129518-01, AI098112, R21 AI138500]
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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.
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