• Call for Social Sciences Papers
  • Sign-up for PNAS eTOC Alerts

Contemporary H3N2 influenza viruses have a glycosylation site that alters binding of antibodies elicited by egg-adapted vaccine strains

  1. Scott E. Hensleya,1
  1. aDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;
  2. bDepartment of Ecology and Evolution, University of Chicago, Chicago, IL 60637;
  3. cDepartment of Medicine, University of Chicago, Chicago, IL 60637;
  4. dDepartment of Medicine, University of Rochester Medical Center, Rochester, NY 14642;
  5. eDepartment of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester Medical Center, Rochester, NY 14642
  1. Edited by Peter Palese, Icahn School of Medicine at Mount Sinai, New York, NY, and approved October 12, 2017 (received for review July 11, 2017)

  1. Fig. 2.

    Contemporary H3N2 viruses with T160 HA are antigenically distinct compared with H3N2 viruses with K160 HA. (A) ELISAs were completed to test the binding of 26 anti-H3 human monoclonal antibodies (mAbs) to a 2009 HA, a 2014 HA with T160, and a 2014 HA with K160. All antibodies in this panel were elicited by a 2009 HA following vaccination before the 2010–2011 season. Shown is percent binding of antibodies to the 2014 viruses relative to binding to the 2009 virus. (B) ELISA binding data for an antibody that binds efficiently to virus with K160 HA but not T160 HA is shown. (C) ELISA binding data for an antibody that recognizes a conserved epitope on the HA stalk is shown to verify that ELISA plates were coated with similar amounts of HA antigen.

  2. Fig. 3.

    Ferrets elicit different types of antibody responses when exposed to H3 viruses with K160 HA and T160 HA. Ferrets (n = 3 animals per group) were infected with viruses possessing (A) K160 HA or (B) T160 HA and sera were collected 28 d later. FRNTs were completed using viruses that possessed K160 HA or T160 HA. Neutralization titers are expressed as inverse dilution of sera that reduced foci by 90%. We completed three independent experiments with each sera. Shown are geometric means from the three independent experiments. Statistical significance was determined using a paired Student’s t test.

  3. Fig. 4.

    Vaccine antigens possessing K160 HA and T160 HA elicit different responses in humans. Donors were vaccinated with seasonal influenza vaccines, and sera were collected before and 28 d after vaccination. FRNTs were completed using viruses that possessed T160 HA or K160 HA. (A) Flublok induced higher fold changes to T160 HA than did Flucelvax and Fluzone (P = 0.01 and P = 0.04 in adjusted analysis, respectively; Table S3; ns, nonsignificant). (B) The vaccine types did not differ in their ability to induce responses to K160 HA (P > 0.1 in adjusted analysis; Table S3). Thick horizontal lines show the median fold changes of the geometric mean titers. Colored rectangles indicate the interquartile range, and whiskers indicate the 150% interquartile ranges. Individual data points are superimposed. See Table S2 for raw titer data.

Online Impact

                                      1. 99132880 2018-01-23
                                      2. 802899879 2018-01-23
                                      3. 295573878 2018-01-23
                                      4. 352668877 2018-01-23
                                      5. 984633876 2018-01-23
                                      6. 545928875 2018-01-23
                                      7. 976569874 2018-01-23
                                      8. 871324873 2018-01-23
                                      9. 263462872 2018-01-23
                                      10. 577161871 2018-01-23
                                      11. 255603870 2018-01-23
                                      12. 117346869 2018-01-23
                                      13. 90982868 2018-01-23
                                      14. 663415867 2018-01-23
                                      15. 793874866 2018-01-23
                                      16. 843582865 2018-01-23
                                      17. 864971864 2018-01-22
                                      18. 258841863 2018-01-22
                                      19. 957295862 2018-01-22
                                      20. 553518861 2018-01-22