Adjuvanted influenza vaccine dynamics

César Parra-Rojas,Veronika Von Messling,Esteban A Hernandez-Vargas

doi:10.1038/s41598-018-36426-9

César Parra-Rojas, Veronika Von Messling + Show 1 more

Open Access

https://doi.org/10.1038/s41598-018-36426-9

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Abstract

Adjuvanted influenza vaccines constitute a key element towards inducing neutralizing antibody responses in populations with reduced responsiveness, such as infants and elderly subjects, as well as in devising antigen-sparing strategies. In particular, squalene-containing adjuvants have been observed to induce enhanced antibody responses, as well as having an influence on cross-reactive immunity. To explore the effects of adjuvanted vaccine formulations on antibody response and their relation to protein-specific immunity, we propose different mathematical models of antibody production dynamics in response to influenza vaccination. Data from ferrets immunized with commercial H1N1pdm09 vaccine antigen alone or formulated with different adjuvants was instrumental to adjust model parameters. While the affinity maturation process complexity is abridged, the proposed model is able to recapitulate the essential features of the observed dynamics. Our numerical results suggest that there exists a qualitative shift in protein-specific antibody response, with enhanced production of antibodies targeting the NA protein in adjuvanted versus non-adjuvanted formulations, in conjunction with a protein-independent boost that is over one order of magnitude larger for squalene-containing adjuvants. Furthermore, simulations predict that vaccines formulated with squalene-containing adjuvants are able to induce sustained antibody titers in a robust way, with little impact of the time interval between immunizations.

Highlights

Adjuvanted influenza vaccines constitute a key element towards inducing neutralizing antibody responses in populations with reduced responsiveness, such as infants and elderly subjects, as well as in devising antigen-sparing strategies
We found that this variant of the model is able to account for the patterns appearing in the data—as can be seen from Fig. S1, this is true for model 0, which does not treat NA- and HA-specific antibodies separately
We see that the response decays and approaches the detection limit towards 130 days post immunization, which does not happen in the cases of MF59- and AS03-adjuvanted formulations

Summary

Introduction

Adjuvanted influenza vaccines constitute a key element towards inducing neutralizing antibody responses in populations with reduced responsiveness, such as infants and elderly subjects, as well as in devising antigen-sparing strategies. Influenza A viruses are classified into subtypes according to the antigenicity of their two main surface glycoproteins: hemagglutinin (HA) and neuraminidase (NA) The former is responsible for virus entry by binding to sialic acids on the surface of hosts cells and subsequent pH-dependent fusion of the viral and endosomal membranes, while the latter mediates the release of newly produced virions from infected cells by removing sialic acid from their surfaces[4,5,6]. Due to these different functions, neutralizing antibodies are primarily directed against the HA protein[7]. The mutation rate in NA is lower than that in HA12—that is, NA is more antigenetically conserved—possibly owing to the fact that the antibody response is skewed towards HA, resulting in a greater selection pressure[6,13]

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