546. Peripheral Follicular Helper T cell Numbers Correlate with Antibody Responses after Immunization with Trivalent Inactivated Influenza Vaccine (TIV)
Session: Poster Abstract Session: Influenza Vaccines
Friday, October 21, 2011
Room: Poster Hall B1
Background: CD4+ Follicular Helper T cells (Tfh) are characterized by the expression of CXCR5, which defines their follicular homing capability. Tfh cells are located on secondary lymphoid organs where they help B cells. CXCR5+CD4+ Th cells are considered counterparts of Tfh in peripheral blood. To date, there is limited information of their role in response to vaccination. We sought to characterize the peripheral CD4+CXCR5+ Th cells response induced by TIV in previously healthy children and to correlate them with B cells and antibody responses.

Methods: Healthy children were immunized with TIV (2010-2011). Peripheral blood was obtained and analyzed by multiparameter flow cytometry on days 0 (baseline; pre-vaccination) 7, 30 and 90 (post-vaccination). We analyzed the differences in cell numbers and activation of total Tfh cells (CD4+CXCR5+CD45RA-) and Tfh subtypes: Tfh 1 (CXCR3+CCR6-), Tfh2 (CXCR3-CCR6-), Tfh17 (CCR6+CXCR3-) cells, ICOS expression (activation) and numbers of plasmablasts (CD19+CD27+CD38+). Serum antibodies titers were measured by hemagglutinin inhibition assay (HAI) on days 0 and 30 after immunization.

Results: We enrolled 20 children, median age 11 years old (range: 4-15 years), 12 were males and 8 femalesAt day 7 post-immunization we observed an increased on absolute numbers of Tfh1 cells but not on the Tfh2 or Tfh17 subsets. Analysis of ICOS expression revealed an increased numbers only of ICOS+ Tfh1 cells suggesting an increased number of activated Tfh1 cells induced by vaccination. Furthermore, we observed a significant correlation between numbers of Tfh1 cells on day 7 and plasmablasts (r=0.470; p=0.04) on day 30 as well as ICOS+Tfh1 cell numbers with antibodies titers (r=0.54; p<0.01) post-vaccination.

Conclusion: These results suggest that TIV induced a robust early Tfh1 immune response, demonstrated by the increased number and activation of this Tfh cell subset on day 7 after immunization, which correlated with B cell responses as determined by the number plasmablasts and antibody titers.


Subject Category: I. Adult and Pediatric Vaccines

Santiago M.C. López, MD1, Emilio Flaño, PhD1, Gerlinde Obermoser, MD2, Raj Ranganathan2, Sara Mertz1, Shelli Farley3, Adolfo Garcia-Sastre, PhD4, Randy Albrecht, PhD5, Asuncion Mejias, MD, PhD6 and Octavio Ramilo, MD7, (1)Center of Vaccines & Immunity, The Research Institute of the Nationwide Children's Hospital, Columbus, OH, (2)Baylor Institute for Immunology Research, Dallas, TX, (3)Department of Clinical Research of the Nationwide Children's Hospital, Columbus, OH, (4)Mount Sinai School of Medicine, New York, NY, (5)Department of Microbiology, Mount Sinai School of Medicine, New York, NY, (6)Pediatrics, Infectious Diseases, Nationwide Children's Hospital, Columbus, OH, (7)Pediatrics, Infectious Diseases, Nationwide Children's Hospital and The Ohio State University College of Medicine, Columbus, OH

Disclosures:

S. M. C. López, None

E. Flaño, None

G. Obermoser, None

R. Ranganathan, None

S. Mertz, None

S. Farley, None

A. Garcia-Sastre, None

R. Albrecht, None

A. Mejias, Abbott: Speaker honorarium, Research grant
Mead-Johnson: Investigator, Research grant

O. Ramilo, Medimmune: Advisory board, Research grant
Abott Labs: Consultant and Speaker's Bureau, honorarium
Abbott Molecular: Consultant, Consulting fee
Merck: Consultant, Consulting fee

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