Vaccine immunity can drive eosinophil recruitment in influenza breakthrough infection with mouse strain–specific outcomes
Year: 2026
Type: article
Abstract: Eosinophils are pleiotropic cells and can respond to a wide array of inflammatory stimuli, including respiratory viral infection. Although they are historically associated with adverse outcomes in vaccinated hosts after breakthrough infection, such as during vaccine-associated enhanced respiratory disease (VAERD) for respiratory syncytial virus (RSV), eosinophils can also help mediate antiviral immunity. We previously observed mild, nonpathological lung eosinophilia in vaccinated mice experiencing influenza breakthrough infection, distinct from VAERD. Here, we investigated the factors driving this eosinophil recruitment and their contribution to host outcomes during influenza breakthrough infection. Vaccine-elicited Abs partially mediate eosinophil recruitment to the lungs during infection but do not confer full protection against viral replication or disease. Live viral replication was needed for robust eosinophil recruitment. Furthermore, both CD4 and CD8 T cells were required for optimal eosinophil accumulation in the lungs. Intramuscular vaccination resulted in the induction of a balanced type 1/2 response in the spleen and mainly a type 2 response in the lung upon infection, whereas a type 1 immune response dominated in the lungs of unvaccinated mice upon infection. Eosinophil depletion studies revealed strain-dependent effects: in BALB/c mice, eosinophil depletion did not significantly affect morbidity, viral load, lung inflammation, or lung lesion severity. However, in C57BL/6 mice, eosinophil depletion improved viral control and reduced pro-inflammatory cytokine expression. Our findings highlight the complex interplay among vaccine-induced immunity, eosinophil recruitment, and host genetic background in shaping outcomes during influenza breakthrough infection, with implications for vaccine strategies and immunopathology mitigation in diverse populations.
Source: The Journal of Immunology
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,500
Awards: Adjuvant strategies for universal and multiseasonal influenza vaccine candidates in the context of pre-existing immunity, G1277313600, G1982867042, Eosinophils as Regulators of Host Immunity against Influenza Infections, Impact of mucosal adjuvanted vaccines on virus transmission in preclinical animal models for SARS-CoV-2 and influenza virus infection, 7HP349, an oral integrin activator to augment effectiveness of pre-exposure influenza vaccination, A Miniature Pig Model for the Study of Host-Immune Responses Against Influenza A Virus, Training Program in Mechanisms of Virus-Host Interactions, Translational Immunology Training Program, Combined adjuvant approaches for enhancement of SARS-CoV-2 vaccine efficacy
OpenAlex ID: W7224632697