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Comparison of the Influenza Virus-Specific Effector and Memory B-Cell Responses to Immunization of Children and Adults with Live Attenuated or Inactivated Influenza Virus Vaccines

Sanae Sasaki,^1,2, Maria C. Jaimes,^1,2,, Tyson H. Holmes,³ Cornelia L. Dekker,⁴ Kutubuddin Mahmood,⁵ George W. Kemble,⁵ Ann M. Arvin,⁴ and Harry B. Greenberg^1,2*

Departments of Medicine and Microbiology and Immunology, Stanford University School of Medicine, Stanford, California,¹ Veterans Affairs Palo Alto Health Care System, Palo Alto, California,² Department of Health Research and Policy, Division of Biostatistics, Stanford University School of Medicine, Stanford, California,³ Department of Pediatrics, Stanford University School of Medicine, Stanford, California,⁴ MedImmune Vaccines, Inc., Mountain View, California⁵

Received 7 September 2006/ Accepted 11 October 2006

Cellular immune responses to influenza virus infection and influenza virus vaccination have not been rigorously characterized. We quantified the effector and memory B-cell responses in children and adults after administration of either live attenuated (LAIV) or inactivated (TIV) influenza virus vaccines and compared these to antibody responses. Peripheral blood mononuclear cells were collected at days 0, 7 to 12, and 27 to 42 after immunization of younger children (6 months to 4 years old), older children (5 to 9 years old), and adults. Influenza virus-specific effector immunoglobulin A (IgA) and IgG circulating antibody-secreting cells (ASC) and stimulated memory B cells were detected using an enzyme-linked immunospot assay. Circulating influenza virus-specific IgG and IgA ASC were detected 7 to 12 days after TIV and after LAIV immunization. Seventy-nine percent or more of adults and older children had demonstrable IgG ASC responses, while IgA ASC responses were detected in 29 to 53% of the subjects. The IgG ASC response rate to LAIV immunization in adults was significantly higher than the response rate measured by standard serum antibody assays (26.3% and 15.8% by neutralization and hemagglutination inhibition assays, respectively). IgG ASC and serum antibody responses were relatively low in the younger children compared to older children and adults. TIV, but not LAIV, significantly increased the percentage of circulating influenza virus-specific memory B cells detected at 27 to 42 days after immunization in children and adults. In conclusion, although both influenza vaccines are effective, we found significant differences in the B-cell and antibody responses elicited after LAIV or TIV immunization in adults and older children and between young children and older age groups.

Published ahead of print on 18 October 2006.

S.S. and M.C.J. contributed equally to this work.

Present address: BD Biosciences, San Jose, Calif.