摘要:SummaryCD4+ T cells play an important role in the maturation of the antibody responses. Conjugation of identified CD4+ T cell helper epitope to the target antigen has been developed as a strategy to enhance vaccine-induced humoral immunity. In this work, we reported the identification of a novel HLA-IAb helper epitope LS-3 fromAquifex aeolicus.In silicoanalysis predicted this epitope to have high binding affinity to common human HLA alleles and have complementary binding coverage to the established PADRE epitope. Introduction of HLA-IAb knockout mutations to the LS-3 epitope significantly attenuated humoral responses induced by a vaccine containing this epitope. Finally, engineered fusion of the epitope to a model antigen, influenza hemagglutinin, significantly improved both binding and hemagglutination inhibition antibody responses in mice receiving DNA or protein vaccines. In summary, LS-3 and additional identified CD4+ helper epitopes may be further explored to improve vaccine responses in translational studies.Graphical AbstractDisplay OmittedHighlights•Identification of a novel CD4+ helper epitope, LS-3, fromAquifex aeolicus•In silicoanalysis predicts high binding affinity of LS-3 to human HLA-DR alleles•Fusing LS-3 to antigen enhances humoral response by vaccinationsImmunology; Cell Biology