Comparison of neuraminidase inhibiting antibody responses elicited by egg- and cell-derived influenza vaccines.

Neuraminidase (NA)-specific antibodies contribute to immunity against influenza. While studies have demonstrated increased NA inhibiting (NAI) antibody titers after vaccination with egg-derived inactivated influenza vaccines (eIIV), the response to cell culture-derived (c) IIV has not been reported. An immunogenicity sub-study was performed within a clinical trial comparing the effectiveness of egg, cell, and recombinant hemagglutinin (HA)-derived influenza vaccines during the 2018-2019 and 2019-2020 influenza seasons. NAI and neutralizing antibody titers against the A(H1N1)pdm09 and A(H3N2) components of the vaccines were measured in pre- and post-vaccination sera. Responses to the N1 component of eIIV and cIIV were different in both study years 1 and 2 whereas response rate and antibody titers to the N2 component of egg and cell culture-derived vaccines were similar. For example, 43.5 % of eIIV and no cIIV recipients had four-fold NAI titer increases in year 1. There was a weak positive correlation between responses to N1 and N2 for both vaccine types but no correlation between NAI and HA-specific neutralizing antibody responses. Recombinant HA vaccine that does not contain NA served as a specificity control; NAI antibody titers did not increase in recipients except in two individuals presumed to have subclinical infection. Antibody responses to NA following vaccination with eIIV and cIIV were not the same; although the responses to the N1 and N2 components of eIIV were similar, there were fewer responders to N1 than N2 of cIIV. Studies to determine the impact of NA immunity on influenza vaccine effectiveness are warranted.

Alvarado-Facundo E ，Herrup R ，Wang W ，Colombo RE ，Collins L ，Ganesan A ，Hrncir D ，Lalani T ，Markelz AE ，Maves RC ，McClenathan B ，Mende K ，Richard SA ，Schmidt K ，Schofield C ，Seshadri S ，Spooner C ，Coles CL ，Burgess TH ，Weiss CD ，Eichelberger M ... -  《-》

Antibody response to sequential vaccination with cell culture, recombinant, or egg-based influenza vaccines among U.S. adults.

Boyce TG ，Levine MZ ，McClure DL ，King JP ，Flannery B ，Nguyen HQ ，Belongia EA ... -  《-》

Erratum: Eyestalk Ablation to Increase Ovarian Maturation in Mud Crabs.

《Jove-Journal of Visualized Experiments》

Quantifying the impact of pre-vaccination titre and vaccination history on influenza vaccine immunogenicity.

Epidemiological studies suggest that heterogeneity in influenza vaccine antibody response can be associated with specific host factors, including pre-vaccination immune status, age, gender, and vaccination history. However, the pattern of reported associations varies between studies. To better understand the underlying influences on antibody responses, we combined host factors and vaccine-induced in-host antibody kinetics from a cohort study conducted across multiple seasons with a unified analysis framework. We developed a flexible individual-level Bayesian model to estimate associations and interactions between host factors, including pre-vaccine HAI titre, age, sex, vaccination history and study setting, and vaccine-induced HAI titre antibody boosting and waning. We applied the model to derive population-level and individual effects of post-vaccine antibody kinetics for A(H1N1) and A(H3N2) influenza subtypes. We found that post-vaccine HAI titre dynamics were significantly influenced by pre-vaccination HAI titre and vaccination history and that lower pre-vaccination HAI titre results in longer durations of seroprotection (HAI titre equal to 1:40 or higher). We also observed that the effect of vaccination history on antibody boosting was stronger for egg-grown A(H1N1) vaccinating strains in individuals with higher pre-vaccination HAI titres, whereas this effect diminished for egg-grown A(H3N2) vaccinating strains. Consequently, for cell-grown A(H1N1), our inference finds that the expected duration of seroprotection post-vaccination was 171 (95 % Posterior Predictive Interval[PPI] 128-220) and 159 (95 % PPI 120-200) days longer for those who are infrequently vaccinated (<2 vaccines in last five years) compared to those who are frequently vaccinated (2 or more vaccines in the last five years) at pre-vaccination HAI titre values of 1:10 and 1:20 respectively. In addition, we found significant differences in the empirical distributions that describe the individual-level duration of seroprotection for A(H1N1) cell-grown strains. In future, studies that rely on serological endpoints should include the impact of pre-vaccine HAI titre and prior vaccination status on seropositivity and seroconversion estimates, as these can significantly influence an individual's post-vaccination antibody kinetics.

Hodgson D ，Sánchez-Ovando S ，Carolan L ，Liu Y ，Hadiprodjo AJ ，Fox A ，Sullivan SG ，Kucharski AJ ... -  《-》

The role of influenza Hemagglutination-Inhibition antibody as a vaccine mediator in children.

Influenza vaccination may protect through the humoral immune response, cellular immune response, or possibly both. Immunity after vaccination can be mediated through antibodies that may be detected by the rise of serum hemagglutination inhibition (HAI) titers. Our objective was to investigate the proportion of protection against influenza mediated through antibodies by measuring the rise of HAI titer (indirect effect) compared to that induced through other immune mechanisms (direct effect) for influenza A and B. We analysed data from a cluster randomized trial conducted during the 2008-2009 season in which Canadian Hutterite children were vaccinated against influenza. We used inverse probability weighting to calculate the indirect and direct effect of vaccination against influenza A/H3N2 and influenza B/Brisbane using HAI titres and overall vaccine efficacy. We included data on 617 children from 46 Hutterite colonies, aged between 3 and 15 years who were vaccinated with either inactivated trivalent influenza vaccine or hepatitis A vaccine. Vaccine efficacy was 63 % for influenza A (H3N2) and 28 % for influenza B. The hazard ratio for protection against influenza A/H3N2 due to an indirect effect of vaccination was 0.96 (95 % confidence interval (CI) of 0.00 to 2.89) while for the direct effect it was 0.38 (95 % CI of 0.00 to 5.47). The hazard ratio for influenza B indirect effect was 0.75 (95 % CI of 0.07 to 1) and for the direct effect 0.96 (95 % CI of 0.00 to 12.02). In contrast, repeating the analysis using microneutralization in a subgroup of 488 children revealed that the protective effect for vaccination for A/H3N2 was entirely mediated by antibodies but only for 13 % for influenza B. Although vaccination provided higher protective effectiveness against influenza A than B, most of the influenza A vaccine efficacy likely occurred through antibodies other than what could be detected by HAI titres. In contrast, for influenza B, while the HAI titres appeared to mediate most of the vaccine effectiveness, this was not confirmed by microneutralization analysis.

Motaghi S ，Pullenayegum E ，Morgan RL ，Loeb M ... -  《-》