Abstract
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.
Highlights
Influenza is a global public health problem, causing approximately 300,000–650,000 global deaths each year [1]
Antibodies directed against the head domain of the surface glycoprotein hemagglutinin (HA) of influenza virus have proven to be the major source of protective immunity, blocking viral binding to the receptors on the target human cell surface and inhibiting viral entry to target cells
The assays currently used to estimate the HA IgG antibody binding to single HA proteins, such as hemagglutinin inhibition (HAI) [13,14], micro-neutralization (MN) [15,16] and enzyme-linked immunosorbent assay (ELISA), all require a large amount of serum sample in order to test the cross-reactivity against an array of virus strains
Summary
Influenza is a global public health problem, causing approximately 300,000–650,000 global deaths each year [1]. The assays currently used to estimate the HA IgG antibody binding to single HA proteins, such as hemagglutinin inhibition (HAI) [13,14], micro-neutralization (MN) [15,16] and enzyme-linked immunosorbent assay (ELISA), all require a large amount of serum sample in order to test the cross-reactivity against an array of virus strains. An increasing number of bnAbs have been isolated and identified from the B cell repertoire after influenza virus infection and vaccination [31,39], targeting both head and stalk regions of HA. After binding to HA, it quickly interferes with the trimeric structure of HA, which blocks viral cell-to-cell spread This mAb offered protection from influenza virus infection in vivo, but it did not display neutralizing activity in HAI or MN assay in vitro studies [51]. During antibody screening, these assays most likely omit bcAbs, such as the human mAb FluA-20 [51], as we discussed above, did not display neutralizing activity in MN assay in vitro
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