Atypical antibody responses to influenza

Abstract

Influenza viruses undergo rapid antigenic evolution and reassortment, resulting in annual epidemics and the occasional pandemics. Exposure to influenza virus hemagglutinin (HA) and neuraminidase (NA) antigen, either through vaccination or infection, induces an antibody response able to recognize only the homologous antigenic subtype. However, atypical antibody responses recognizing non-homologous influenza subtypes have been reported during infection and vaccination. Here, we review the incidence of these phenomena in published literature and discuss the potential mechanisms underlying them.

Keywords: Influenza; antibody; heterosubtypic; neutralizing.

Figure 1

Structure of the influenza HA protein. (A) Shown in this figure is a group 2 HA (H3 subtype) [Protein Data Bank (PDB) accession number 4FNK]. HA exists as a trimer on the virion surface and is composed of the globular head (colored green on a single monomer) and the conserved stalk region (red). The major antigenic sites and receptor-binding domain (indicated by blue arrow) reside within the globular head. (B) Classification of the HA subtypes. HA, hemagglutinin.

Figure 2

Percentage of heterologous and homologous seroconversion events detected in the FLU09 cohort from 2009 to 2014. Table below indicates the number of influenza-positive participants with paired sera available for testing according to infecting subtypes. Percentages of total Flu +ve are indicated in parentheses. Homologous seroconversion refers to seroconversion event against the infecting influenza subtype (either H1N1, H3N2 or influenza B), as detected by subtyping polymerase-chain-reaction (PCR) method. Heterologous seroconversion refers to seroconversion event to any of the other non-infecting influenza subtypes.

Figure 3

Annual prevalence of influenza viruses, by subtypes, in the United States between 2009 and 2016. With the exception of 2009/2010 and 2010/2011 influenza season, a single subtype typically dominates during peak influenza activity period. During the 2009/2010 season, only A(H1N1)pdm09 circulated while in 2010/2011, both A(H1N1)pdm and H3N2 subtypes were detected at similar proportions. This suggests that co-infections with multiple influenza virus subtypes can occur at low frequencies. Data was retrieved from World Health Organization’s (WHO)’s Global Influenza Surveillance and Response System (GISRS) online reporting portal, FluNet (http://www.who.int/influenza/gisrs_laboratory/flunet/en/).