Adjuvanted inactivated zoonotic influenza A(H5N8) vaccination induces subtype-wide antibody responses in previously immunized individuals

ABSTRACT: Recent human infections with highly pathogenic avian influenza viruses (HPAIV) of the A(H5) hemagglutinin (HA) subtype underscore their pandemic potential, highlighting the need for stockpiled vaccines as a pandemic preparedness measure. The Netherlands obtained the MF59-adjuvanted inactivated A(H5N8) vaccine (manufactured by CSL Seqirus) based on A(H5) clade 2.3.4.4b A/Astrakhan/3212/2020, through a joint European procurement, and offered it to healthcare workers (HCW) at risk of occupational exposure. Given the limited data on the breadth of immune responses induced by this vaccine, this study evaluated antibody and T-cell responses upon vaccination of naïve HCW and HCW previously vaccinated with A(H5) influenza vaccines. As a sub-study of an ongoing observational cohort study, immune responses at baseline and on days 7 and 28 after each of the two vaccine doses were evaluated in 39 HCW. Of those 39 HCW, 6 had been previously vaccinated with A(H5) influenza vaccines containing antigenically distinct HA. HA-binding antibodies were measured via protein microarray (PMA), and functional antibodies were quantified by hemagglutinin inhibition (HI), neuraminidase inhibition (NI), and antibody-dependent cellular cytotoxicity (ADCC) assays. T-cell responses were detected by interferon-gamma release assays (IGRA) and activation-induced marker (AIM) assays. HI antibodies targeting clade 2.3.4.4b A(H5) influenza viruses, including A/Astrakhan/3212/2020 (vaccine antigen) and A/Texas/37/2024 (isolated during the cattle outbreak in the United States), were induced in all naïve HCW. When post-boost sera were tested against 80 antigenically diverse A(H5) influenza viruses from our A(H5) antigenic map (PMID: 41094140) , clade 2.3.4.4b-restricted HI responses were primarily detected in naïve HCW, in contrast to a broad response against almost all tested viruses in previously vaccinated HCW. Additionally, de novo induction of N8-specific antibodies was detected. Most HCW had detectable A(H5)-reactive ADCC antibodies and T-cells at baseline, which were boosted by vaccination. Our findings show that the zoonotic influenza vaccine induced HI antibodies targeting clade 2.3.4.4b A(H5) viruses in naïve HCW. In addition to HI antibodies, the induction of NI antibodies, and boosting of ADCC antibodies and T-cells targeting the vaccine antigen was detected. While naïve individuals developed HI responses restricted to clade 2.3.4.4b, previously vaccinated individuals had broad HI reactivity across all A(H5) clades. This highlights the potential of heterologous prime-boost vaccination strategies to induce broad A(H5) immunity.

ORGANISM(S): Homo sapiens (human)

SUBMITTER: Ted 

PROVIDER: S-BSST2825 | biostudies-other |

REPOSITORIES: biostudies-other