How to assess the effectiveness of nasal influenza vaccines? Role and measurement of sIgA in mucosal secretions

Abstract

Secretory IgAs (sIgA) constitute the principal isotype of antibodies present in nasal and mucosal secretions. They are secreted by plasma cells adjacent to the mucosal epithelial cells, the site where infection occurs, and are the main humoral mediator of mucosal immunity. Mucosally delivered vaccines, such as live attenuated influenza vaccine (LAIV), are able to mimic natural infection without causing disease or virus transmission and mainly elicit a local immune response. The measurement of sIgA concentrations in nasal swab/wash and saliva samples is therefore a valuable tool for evaluating their role in the effectiveness of such vaccines. Here, we describe two standardized assays (enzyme‐linked immunosorbent assay and microneutralization) available for the quantification of sIgA and discuss the advantages and limitations of their use.

Electronic-Cigarette Use Alters Nasal Mucosal Immune Response to Live-attenuated Influenza Virus. A Clinical Trial

“…Previous studies have shown that serum antibody levels are a poor measure of LAIV vaccine efficacy ( 50 ). In contrast, nasal mucosal secretory IgA, the predominant immunoglobulin produced in response to infection of the nasal mucosa, has been shown to be a much better indicator of LAIV-induced antibody responses (reviewed in Reference 45 ). We developed an anti–LAIV-IgA ELISA to determine the effects of cigarette smoking and e-cigarette use on antibody production and found that LAIV-specific IgA levels increased as expected in nonsmokers after LAIV inoculation but did not increase in e-cigarette users and cigarette smokers ( Figure 3B ).…”

“…Considering that e-cigarette use is prevalent among teenagers who are recommended for complete immunization schedules, understanding whether and how vaping could modify vaccination-conferred immunity is an unexplored field. Secretory IgA is the principal antibody isotype present in nasal secretions ( 45 ) and neutralizes pathogens, like influenza, at the site of infection before they attach, enter, and replicate in the host cell ( 45 ). Although conventional intramuscularly administered influenza vaccines generate a serum IgG-antibody response, protection conferred by LAIV vaccination is believed to be derived by its ability to generate a robust and sustained nasal mucosal IgA response ( 51 ).…”

“…Levels of influenza-specific IgA in the NLF were measured using a direct-sandwich ELISA ( see data supplement). Virus-specific IgA levels were determined against the IgA standard curve and normalized to total IgA levels ( 45 ). After normalization, the change in the antibody level was determined by using the relative percentage of the baseline level, in which the virus-specific antibody concentration post-LAIV inoculation was divided by pre-LAIV inoculation levels and multiplied by 100.…”

The Impact of Oral Health on Respiratory Viral Infection

“…SIgA antibodies have neutralization potential pathogens at the entrance site before they can attach to epithelial cells and overcome the epithelial surface. Considerable levels of Influenza virus specific SIgA was secreted in saliva, suggesting that saliva works as humoral immunity against influenza virus [ 20 , 21 ]. The development of mucosal vaccines that aim to induce influenza virus-specific IgA has been working on.…”

Induction of mucosal immunity against pathogens by using recombinant baculoviral vectors: Mechanisms, advantages, and limitations

“…74 In mucosae, technical difficulties in obtaining samples also exist, although standardized methods in our laboratory and by others are optimal. 3,4,75,76 Immunogenicity-the ability of an immunogen to elicit high titers of Abs and T cell proliferation or cytokine secretion-is just the first step on the long way to obtain an efficacious vaccine. 77 One side of the problem is that we still lack enough understanding of the types of immune responses that protect the host from specific pathogens.…”