Assessment of enhanced influenza vaccination finds that FluAd conveys an advantage in mice and older adults

Abstract

Objectives Enhanced inactivated influenza vaccines (eIIV) aim to increase immunogenicity and protection compared with the widely used standard IIV (S‐IIV). Methods We tested four vaccines in parallel, FluZone high dose, FluBlok and FluAd versus S‐IIV in a randomised controlled trial of older adults and in a mouse infection model to assess immunogenicity, protection from lethal challenge and mechanisms of action. Results In older adults, FluAd vaccination stimulated a superior antibody profile, including H3‐HA antibodies that were elevated for up to 1 year after vaccination, higher avidity H3HA IgG and larger HA stem IgG responses. In a mouse model, FluAd also elicited an earlier and larger induction of HA stem antibodies with increased germinal centre responses and upregulation and long‐term expression of B‐cell switch transcription factors. Long‐term cross‐reactive memory responses were sustained by FluAd following lethal heterosubtypic influenza challenge, with reduced lung damage and viral loads, coinciding with increased T‐ and B‐cell recall. Advantages were also noted for the high‐dose FluZone vaccine in both humans and mice. Conclusion The early, broadly reactive and long‐lived antibody response of FluAd indicates a potential advantage of this vaccine, particularly in years when there is a mismatch between the vaccine strain and the circulating strain of influenza viruses.

Selecting and Using the Appropriate Influenza Vaccine for Each Individual

“…However, because of the lack of immunostimulants in these vaccines, the efficacy of the vaccine is also quite low. Therefore, subunit vaccines for the elderly population include an adjuvant (Fluad ® ) to improve the effectiveness of the vaccine [ 39 , 40 ].…”

Next-generation T cell–activating vaccination increases influenza virus mutation prevalence

“…To assess influenza-specific binding antibodies from vaccination, IgG responses specific for H1N1 representative HA and NP recombinant proteins (Sino Biological, China) were determined by enzyme-linked immunosorbent assay (ELISA), as previously described ( 60 ). Data from flow cytometry and ELISA IgG responses with background subtracted are indicated.…”

Repeated influenza vaccination provides cumulative protection from distinct H3N2 viruses

“…Blood was collected by cardiac puncture and clotted (MiniCollect, Greiner Bio‐one, Kremsmünster, Austria), and serum was harvested after centrifugation and aliquoted and heat‐inactivated, at 30 min at 56°C, before all in vitro experiments. To quantify virus replication, antibody and cellular responses, the lungs, BAL, lymphoid organs (mLN for challenged mice or iLN for vaccinated mice) and bone marrow were processed as previously described 30 . Lung viral titres were determined from homogenates by M gene quantification using quantitative RT‐PCR 30 .…”

“…To quantify virus replication, antibody and cellular responses, the lungs, BAL, lymphoid organs (mLN for challenged mice or iLN for vaccinated mice) and bone marrow were processed as previously described 30 . Lung viral titres were determined from homogenates by M gene quantification using quantitative RT‐PCR 30 . All experimental procedures were conducted in accordance with the standards approved by the Committee on the Use of Live Animals in Teaching and Research, the University of Hong Kong.…”

“…Quantitative RT‐PCR (qRT‐PCR) was performed for the murine Blimp1, CXCR4, CD21, on B cells isolated from bone marrow using magnetic B cell isolation kit (Miltenyi Biotec, Bergisch Gladbach, Germany), as previously described 30 . RNA was extracted using RNeasy mini kit (Qiagen, Hilden, Germany), and a reverse transcription using Oligo dT primers with PrimeScript RT reagent kit (TAKARA, Kusatsu, Japan) was performed.…”