Heterotypic Neuraminidase Antibodies Against Different A(H1N1) Strains are Elicited after Seasonal Influenza Vaccination

Abstract

Neuraminidase (NA) content is not standardized in current seasonal influenza vaccines; neither anti-NA antibodies (anti-NA Abs) are measured nor is it well-defined as a correlate of humoral protection. In this work, the presence of NA1 antibodies against classical A(H1N1) and A(H1N1) pdm09 subtypes was studied before and after vaccination with seasonal vaccines containing A/California/07/2009 strain (A(H1N1) pdm09 subtype). By Enzyme-Linked Lectin Assay (ELLA; Consortium for the Standardization of Influenza Seroepidemiology), we analyzed serum samples from two different cohorts (adults and elderly). The presence of anti-NA Abs at titers ≥1/40 against classical A(H1N1) and A(H1N1) pdm09 subtypes were frequently found in both age groups, in 81.3% and 96.3% of adults and elderly, respectively. The higher titers of anti-NA Abs (NAI titers) were detected more frequently against classical A(H1N1) strains according to the expected age when the first flu infection takes place. In this way, an Original Antigenic Sin phenomenon related to NA seems to be part of the immune response against flu. Seasonal-vaccination induced homologous seroconversion against NA of A(H1N1) pdm09 subtype in 52.5% and 55.0%, and increased the Geometric Mean Titers (GMTs) in 70.0% and 78.8% of adults and elderly, respectively. Seasonal vaccination also induced a heterotypic anti-NA Abs response against classical A(H1N1) strains (seroconversion at least in 8.8% and 11.3% of adults and elderly, respectively, and an increase in GMTs of at least 28.0% in both age groups). These anti-NA Abs responses occur even though the seasonal vaccine does not contain a standardized amount of NA. This work demonstrates that seasonal vaccines containing the A(H1N1) pdm09 subtype induce a broad antibody response against NA1, that may be a target for future influenza vaccines. Our study is one of the first to analyze the presence of Abs against NA and the response mediated by NAI titers after seasonal influenza vaccination.

Review of Influenza Virus Vaccines: The Qualitative Nature of Immune Responses to Infection and Vaccination Is a Critical Consideration

“…Similar results were also seen by Mendez-Legaza et al, which looked at NA-specific Abs following various H1N1 infections. The study’s participants exhibited different Ab responses that corresponded to viruses that likely primed their immune system upon the first infection [ 131 ] and the observations provide further evidence of OAS patterns in response to NA.…”

Extending the Stalk Enhances Immunogenicity of the Influenza Virus Neuraminidase

“…The NA undergoes antigenic drift, indicating that the NA is under immune pressure as well (6,21,22). In contrast to anti-HA antibodies and despite the observed antigenic drift in the NA, anti-NA antibodies often cross-react within one subtype, such as N1 (11,(23)(24)(25)(26) or N2 (11,27,28), or among influenza B virus NAs (11,29,30).…”

In planta Production and Validation of Neuraminidase Derived from Genotype 4 Reassortant Eurasian Avian-like H1N1 Virus as a Vaccine Candidate

“…The NA antigen evolves independently of HA [ 9 , 10 ], and NA induces heterologous immunity. For example, cross-protective anti-NA antibodies were generated after a seasonal vaccination with a single influenza viral strain, A/California/07/2009 (subtype A (H1N1) pdm09) [ 11 ]. Due to these beneficial characteristics, NA has been suggested as a good antigen candidate to improve the breadth of vaccine efficacy and is applicable to vaccine design [ 6 ].…”