The Negative Effect of Preexisting Immunity on Influenza Vaccine Responses Transcends the Impact of Vaccine Formulation Type and Vaccination History

• Published in: The Journal of infectious diseases Vol. 227; no. 3; pp. 381 - 390
• Main Authors: Moritzky, Savannah A, Richards, Katherine A, Glover, Maryah A, Krammer, Florian, Chaves, Francisco A, Topham, David J, Branche, Angela, Nayak, Jennifer L, Sant, Andrea J
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01.02.2023
• Subjects: Adult; Antibodies; Antibodies, Viral; CD4 antigen; CD4-Positive T-Lymphocytes; Enzyme-linked immunosorbent assay; Hemagglutinin Glycoproteins, Influenza Virus; Hemagglutinins; Humans; Immunity; Immunological memory; Influenza; Influenza A; Influenza Vaccines; Influenza, Human - prevention & control; Lymphocytes; Lymphocytes B; Lymphocytes T; Major; Memory cells; Vaccination; Vaccines; influenza; CD4 T cells; immune memory; vaccines; human immunity
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jiac068

Abstract The most effective measure to induce protection from influenza is vaccination. Thus, yearly vaccination is recommended, which, together with infections, establishes diverse repertoires of B cells, antibodies, and T cells. We examined the impact of this accumulated immunity on human responses in adults to split, subunit, and recombinant protein-based influenza vaccines. Enzyme-linked immunosorbent assay (ELISA) assays, to quantify serum antibodies, and peptide-stimulated CD4 T-cell cytokine ELISpots revealed that preexisting levels of hemagglutinin (HA)-specific antibodies were negatively associated with gains in antibody postvaccination, while preexisting levels of CD4 T cells were negatively correlated with vaccine-induced expansion of CD4 T cells. These patterns were seen independently of the vaccine formulation administered and the subjects’ influenza vaccine history. Thus, although memory CD4 T cells and serum antibodies consist of components that can enhance vaccine responses, on balance, the accumulated immunity specific for influenza A H1 and H3 proteins is associated with diminished future responses. The impact of accumulated influenza-specific antibodies and CD4 T cells on human responses to influenza vaccines was examined. These studies revealed that, on balance, preexisting immunity specific for influenza A H1 and H3 proteins is associated with diminished future responses.