Mantus 2025 characterized the stem-specific repertoire of individuals vaccinated with one of three group 2 influenza subtypes (H3, H7, or H10), using epitope mapping to identify two complementary epitope supersites on the group 2 HA stem: a central epitope that was broadly cross-reactive and a lower epitope with narrower breadth but higher potency against H3 subtypes. These results suggest that vaccine strategies that target both of these stem epitopes would elicit broader and more potent immune protection against seasonal and pandemic influenza viruses.
Yang 2024 performed a comprehensive structural and biochemical characterization of immune memory on the breadth and diversity of the polyclonal serum Ab response elicited following vaccination with a ferritin nanoparticle vaccine displaying H2 HA in H2-naive and H2-exposed adults. They found that previous H2 exposure results in higher responses to the variable HA head domain. In contrast, initial responses in H2-naive participants are dominated by Abs targeting conserved epitopes.
Martínez 2024 examined the immunodominance hierarchy of the classical antigenic sites of the H1 protein, based on an analysis of HI titers in 39 human serum samples from the Stop Flu NYU cohort. Results indicated the immunodominance profile displayed by each person is strongly associated with the level of HI titers against the A/Michigan/45/2015 strain and that although biological sex does not appear to influence the hierarchy of the antigenic sites, age seems to play a role in the probability of displaying a specific immunodominance profile.
Rijnink 2023 investigated the role of non-neutralizing Abs that target conserved influenza virus proteins in protecting against IAV-induced morbidity and mortality. They identified six human mAbs isolated from two H3N2-infected donors that showed robust binding against the conserved internal NP and M1 of IAV strains and passively transferred these mAbs to mice. Results suggested that human NP and M1 antibodies that are elicited following IAV infection/vaccination do not protect from substantial weight loss in the mouse model and imply that protection afforded targeting these antigens following vaccination/infection is most likely the result of cellular-based immunity.
Sicca 2022 evaluated preexisting immunity against IAV by determining levels of nAbs and binding Abs to five strains of IAV in three age cohorts (young, adult, and elderly) at two time-points five years apart. Results demonstrated that in each age cohort, the highest nAb titers were seen for a virus strain that circulated early in life but the highest increase in titer was found for the most recent virus strains. In contrast, the highest virus-binding (IgG) titers were seen against recent virus strains but the biggest increase in titer occurred against older strains; and significant increases in nAb titers against a newly encountered virus strain were observed in all age cohorts demonstrating that pre-existing immunity did not hamper Ab induction.