Abstract
At the moment, developing new broad-spectrum influenza vaccines which would help avoid annual changes in a vaccine’s strain set is urgency. In addition, developing new vaccines based on highly conserved influenza virus proteins could allow us to better prepare for potential pandemics and significantly reduce the damage they cause. Evaluation of the humoral response to vaccine administration is a key aspect of the characterization of the effectiveness of influenza vaccines. In the development of new broad-spectrum influenza vaccines, it is important to study the mechanisms of action of various antibodies, including non-neutralizing ones, as well as to be in the possession of methods for quantifying these antibodies after immunization with new vaccines against influenza. In this review, we focused on the mechanisms of anti-influenza action of non-neutralizing antibodies, such as antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and antibody-mediated complement-dependent cytotoxicity (CDC). The influenza virus antigens that trigger these reactions are hemagglutinin (HA) and neuraminidase (NA), as well as highly conserved antigens, such as M2 (ion channel), M1 (matrix protein), and NP (nucleoprotein). In addition, the mechanisms of action and methods for detecting antibodies to neuraminidase (NA) and to the stem domain of hemagglutinin (HA) of the influenza virus are considered.
Highlights
Influenza is a highly contagious infection; it is responsible for annual epidemics and periodical pandemics that appear at varied intervals
A study of the antibody-dependent cellular phagocytosis (ADCP) mechanism in the influenza infection showed that both macrophages and neutrophils are quickly recruited to the lungs and are present in bronchoalveolar lavage, the respiratory tract, and alveoli, where they contribute to the rapid scavenging of infected and dead cells
It is assumed that each subsequent influenza infection, as well as influenza vaccinations, slightly induces the cross-reactive antibodies involved in ADCP, with their level increasing with each subsequent influenza infection [17]
Summary
Influenza is a highly contagious infection; it is responsible for annual epidemics and periodical pandemics that appear at varied intervals. Many HA head-specific antibodies are able to inhibit the release of the virus from the cell (Fig. 1, d) This defense mechanism cannot be evaluated by conventional hemagglutination inhibition and neutralization inhibition assays; it is detected by adding antibodies to cells that have been previously infected with the influenza virus [7]. Antibodies against various conserved antigens of the influenza virus (such as NP, M1, M2) are generally nonneutralizing in nature and cannot prevent the development of the viral infection They are able to exert a protective function through various immune mechanisms. It has been shown that antibodies with a broad spectrum of activity against the conserved HA stem protect mice from a lethal influenza infection through a mechanism that involves an interaction with Fc-FcγR. Elderly people who had previously been infected with viruses close to the strain that caused the 2009 swine influenza pandemic and who retained a significant amount of titers of the antibodies participating in ADCC but had no neutralizing antibodies were
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