Influenza-like Illness Incidence Is Not Reduced by Influenza Vaccination in a Cohort of Older Adults, Despite Effectively Reducing Laboratory-Confirmed Influenza Virus Infections.

Background: Data on the relative contribution of influenza virus and other respiratory pathogens to respiratory infections in community-dwelling older adults (≥60 years) are needed. Methods: A prospective observational cohort study was performed in the Netherlands during 2 winters. Nasopharyngeal and oropharyngeal swabs were collected during influenza-like illness (ILI) episodes and from controls. Viruses and bacteria were identified by multiplex ligation-dependent probe amplification assay and conventional bacterial culture. Results: The ILI incidence in the consecutive seasons was 7.2% and 11.6%, and influenza virus caused 18.9% and 34.2% of ILI episodes. Potential pathogen were detected in 80% of the ILI events with influenza virus, coronaviruses, rhinoviruses, human metapneumovirus, respiratory syncytial virus, parainfluenza viruses, and Haemophilus influenzae being the most common. Influenza vaccination reduced influenza virus infection by 73% (95% confidence interval [CI], 26%-90%) and 51% (95% CI, 7%-74%) in ILI patients. However, ILI incidence was similar between vaccinated (7.6% and 10.8%) and nonvaccinated (4.2% and 11.4%) participants in 2011-2012 and 2012-2013, respectively (P > .05). Conclusions: Influenza virus is a frequent pathogen in older adults with ILI. Vaccination reduces the number of influenza virus infections but not the overall number of ILI episodes: other pathogens fill the gap. We suggest the existence of a pool of individuals with high susceptibility to respiratory infections. Clinical Trials Registration: NTR3386.

Contribution of Influenza Viruses, Other Respiratory Viruses and Viral Co-Infections to Influenza-like Illness in Older Adults.

Influenza-like illness (ILI) can be caused by a range of respiratory viruses. The present study investigates the contribution of influenza and other respiratory viruses, the occurrence of viral co-infections, and the persistence of the viruses after ILI onset in older adults. During the influenza season 2014-2015, 2366 generally healthy community-dwelling older adults (≥60 years) were enrolled in the study. Viruses were identified by multiplex ligation-dependent probe-amplification assay in naso- and oropharyngeal swabs taken during acute ILI phase, and 2 and 8 weeks later. The ILI incidence was 10.7%, which did not differ between vaccinated and unvaccinated older adults; influenza virus was the most frequently detected virus (39.4%). Other viruses with significant contribution were: rhinovirus (17.3%), seasonal coronavirus (9.8%), respiratory syncytial virus (6.7%), and human metapneumovirus (6.3%). Co-infections of influenza virus with other viruses were rare. The frequency of ILI cases in older adults in this 2014-2015 season with low vaccine effectiveness was comparable to that of the 2012-2013 season with moderate vaccine efficacy. The low rate of viral co-infections observed, especially for influenza virus, suggests that influenza virus infection reduces the risk of simultaneous infection with other viruses. Viral persistence or viral co-infections did not affect the clinical outcome of ILI.

Immunogenicity of Influenza Vaccines: Evidence for Differential Effect of Secondary Vaccination on Humoral and Cellular Immunity.

While currently used influenza vaccines are designed to induce neutralizing antibodies, little is known on T cell responses induced by these vaccines. The 2009 pandemic provided us with the opportunity to evaluate the immune response to vaccination in a unique setting. We evaluated both antibody and T cell responses in a cohort of public health care workers (18-52 years) during two consecutive influenza seasons from 2009 to 2011 and compared the MF59-adjuvanted pandemic vaccine with the unadjuvanted seasonal subunit vaccine that included the pandemic strain [The study was registered in the Netherlands Trial Register (NTR2070)]. Antibody responses were determined in serum by a hemagglutination inhibition assay. Vaccine-specific T cell responses were evaluated by detecting IFN-γ producing peripheral blood mononuclear cells using whole influenza virus or vaccine-specific peptide pools as stimulating antigens. Mixed effects regression models were used to correct the data for influenza-specific pre-existing immunity due to previous infections or vaccinations and for age and sex. We show that one dose of the pandemic vaccine induced antibody responses sufficient for providing seroprotection and that the vaccine induced T cell responses. A second dose further increased antibody responses but not T cell responses. Nonetheless, both could be boosted by the seasonal vaccine in the subsequent season. Furthermore, we show that the seasonal vaccine alone is capable of inducing vaccine-specific T cell responses, despite the fact that the vaccine did not contain an adjuvant. In addition, residual antibody levels remained detectable for over 15 months, while T cell levels in the blood had contracted to baseline levels by that time. Hereby, we show that pandemic as well as seasonal vaccines induce both humoral and cellular responses, however, with a different profile of induction and waning, which has its implications for future vaccine design.

Safety and immunogenicity of influenza whole inactivated virus vaccines: A phase I randomized clinical trial.

BACKGROUND: Influenza vaccine production capacity is still insufficient to meet global demand in case of a pandemic. To expand worldwide influenza vaccine production capacity, a solid and transferable egg-based influenza vaccine production process was established that is suitable for upscaling and technology transfer to vaccine manufacturers in low- and middle-income countries. As a proof-of-concept, the safety and immunogenicity of a pandemic whole inactivated virus (WIV) vaccine (H5N1) and a monovalent seasonal WIV vaccine (H3N2) were evaluated in a phase I clinical trial in adults. METHODS: Subjects were vaccinated with 2 doses of pandemic WIV vaccine (pWIV), or one dose of either seasonal WIV vaccine (sWIV) or a commercially available trivalent comparator vaccine followed by a placebo dose. Haemagglutination inhibiting antibody titres against the influenza strains were determined before and 21 d after each vaccination. RESULTS: The frequency and severity of adverse reactions were comparable between groups. No serious adverse events were reported. After a single dose of sWIV the seroconversion rate was 91% (Committee for Proprietary Medicinal Products (CPMP) criterion >40%), the seroprotection rate was 100% (CPMP criterion >70%), and the mean geometric mean titre (GMT) increase was 24.9 (CPMP criterion >2.5). After two doses of pWIV, seroconversion rate and seroprotection rate were both 71%, and the mean GMT increase was 7.8. CONCLUSIONS: Both pWIV and sWIV were equally well-tolerated as the comparator vaccine, and both vaccines complied with all 3 CPMP criteria. EudraCT 2011-000159-17. Netherlands National Trial Register 2695.