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

ABSTRACT 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.

[1]  D. Lewis,et al.  Cellular Immune Responses in Children and Adults Receiving Inactivated or Live Attenuated Influenza Vaccines , 2006, Journal of Virology.

[2]  M. Sidhu,et al.  Genetic and phenotypic stability of cold-adapted influenza viruses in a trivalent vaccine administered to children in a day care setting. , 2006, Virology.

[3]  Siep Thomas,et al.  Influenza-associated deaths among children. , 2006, The New England journal of medicine.

[4]  Cécile Viboud,et al.  Antibody response to influenza vaccination in the elderly: a quantitative review. , 2006, Vaccine.

[5]  Susanna Esposito,et al.  Clinical and economic impact of influenza vaccination on healthy children aged 2-5 years. , 2006, Vaccine.

[6]  M. Quiding-Järbrink,et al.  Differential expression of chemokine receptors on human IgA+ and IgG+ B cells , 2005, Clinical and experimental immunology.

[7]  A. Razmpour,et al.  LIVE ATTENUATED INFLUENZA VACCINE INDUCES CROSS-REACTIVE ANTIBODY RESPONSES IN CHILDREN AGAINST AN A/FUJIAN/411/2002-LIKE H3N2 ANTIGENIC VARIANT STRAIN , 2004, The Pediatric infectious disease journal.

[8]  Keiji Fukuda,et al.  Influenza-associated hospitalizations in the United States. , 2004, JAMA.

[9]  R. Walker,et al.  Measuring Antibody Responses to a Live Attenuated Influenza Vaccine in Children , 2004, The Pediatric infectious disease journal.

[10]  R. Ahmed,et al.  Immunological memory in humans. , 2004, Seminars in immunology.

[11]  R. Ahmed,et al.  Tracking human antigen-specific memory B cells: a sensitive and generalized ELISPOT system. , 2004, Journal of immunological methods.

[12]  K. Nichol,et al.  Cost benefit of influenza vaccination in healthy, working adults: an economic analysis based on the results of a clinical trial of trivalent live attenuated influenza virus vaccine. , 2003, Vaccine.

[13]  Antonio Lanzavecchia,et al.  Maintenance of Serological Memory by Polyclonal Activation of Human Memory B Cells , 2002, Science.

[14]  Keiji Fukuda,et al.  Mortality associated with influenza and respiratory syncytial virus in the United States. , 2003, JAMA.

[15]  Eric R. Ziegel,et al.  Generalized Linear Models , 2002, Technometrics.

[16]  Jonathan Dushoff,et al.  Hemagglutinin sequence clusters and the antigenic evolution of influenza A virus , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[17]  R. Jonsson,et al.  Parenteral vaccination against influenza does not induce a local antigen-specific immune response in the nasal mucosa. , 2002, The Journal of infectious diseases.

[18]  A. Osterhaus,et al.  Cold-adapted live influenza vaccine versus inactivated vaccine: systemic vaccine reactions, local and systemic antibody response, and vaccine efficacy. A meta-analysis. , 2002, Vaccine.

[19]  E. Butcher,et al.  Expression of α4β7 and E‐selectin ligand by circulating memory B cells: implications for targeted trafficking to mucosal and systemic sites , 2000, Journal of Leukocyte Biology.

[20]  W. Gruber,et al.  Prevention of otitis media in children with live attenuated influenza vaccine given intranasally. , 2000, The Pediatric infectious disease journal.

[21]  Lihan K. Yan,et al.  Correlates of immune protection induced by live, attenuated, cold-adapted, trivalent, intranasal influenza virus vaccine. , 2000, The Journal of infectious diseases.

[22]  John J. Treanor,et al.  Efficacy and Safety of the Oral Neuraminidase Inhibitor Oseltamivir in Treating Acute Influenza , 2000 .

[23]  R. Betts,et al.  Evaluation of trivalent, live, cold-adapted (CAIV-T) and inactivated (TIV) influenza vaccines in prevention of virus infection and illness following challenge of adults with wild-type influenza A (H1N1), A (H3N2), and B viruses. , 1999, Vaccine.

[24]  J. Wittes,et al.  Effectiveness of live, attenuated intranasal influenza virus vaccine in healthy, working adults: a randomized controlled trial. , 1999, JAMA.

[25]  A. Kantele,et al.  Homing potentials of circulating antibody-secreting cells after administration of oral or parenteral protein or polysaccharide vaccine in humans. , 1999, Vaccine.

[26]  R. Cox,et al.  Systemic and mucosal immune responses in young children and adults after parenteral influenza vaccination. , 1998, The Journal of infectious diseases.

[27]  F. Hayden,et al.  The efficacy of live attenuated, cold-adapted, trivalent, intranasal influenzavirus vaccine in children. , 1998, The New England journal of medicine.

[28]  B. Everitt,et al.  Analysis of longitudinal data , 1998, British Journal of Psychiatry.

[29]  L H Moulton,et al.  A mixture model with detection limits for regression analyses of antibody response to vaccine. , 1995, Biometrics.

[30]  J. H. Schuenemeyer,et al.  Generalized Linear Models (2nd ed.) , 1992 .

[31]  A. Agresti [A Survey of Exact Inference for Contingency Tables]: Rejoinder , 1992 .

[32]  Muni S. Srivastava,et al.  Regression Analysis: Theory, Methods, and Applications , 1991 .

[33]  P. McCullagh,et al.  Generalized Linear Models, 2nd Edn. , 1990 .

[34]  W. Beyer,et al.  Antibody induction by influenza vaccines in the elderly: a review of the literature. , 1989, Vaccine.

[35]  B. Murphy,et al.  Serum and nasal wash antibodies associated with resistance to experimental challenge with influenza A wild-type virus , 1986, Journal of clinical microbiology.

[36]  P. Wright,et al.  Immunity to influenza A virus infection in young children: a comparison of natural infection, live cold-adapted vaccine, and inactivated vaccine. , 1986, The Journal of infectious diseases.

[37]  P. Wright,et al.  Comparison of long‐term systemic and secretory antibody responses in children given live, attenuated, or inactivated influenza A vaccine , 1985, Journal of medical virology.

[38]  D. Nelson,et al.  Human peripheral blood mononuclear cells produce IgA anti-influenza virus antibody in a secondary in vitro antibody response. , 1985, Journal of Immunology.

[39]  B. Murphy,et al.  In vitro production of anti-influenza virus antibody after intranasal inoculation with cold-adapted influenza virus. , 1981, Journal of immunology.

[40]  R. Callard Specific in vitro antibody response to influenza virus by human blood lymphocytes , 1979, Nature.

[41]  N. Jaspen Applied Nonparametric Statistics , 1979 .

[42]  Andreas Radbruch,et al.  Maintenance of serum antibody levels. , 2005, Annual review of immunology.

[43]  S. Block Role of Influenza Vaccine For Healthy Children in the US , 2004, Paediatric drugs.

[44]  R. Couch An overview of serum antibody responses to influenza virus antigens. , 2003, Developments in biologicals.

[45]  T. Szucs Influenza. The role of burden-of-illness research. , 1999, PharmacoEconomics.

[46]  Glezen Wp Emerging Infections: Pandemic Influenza , 1996 .

[47]  Glezen Wp,et al.  Emerging infections: pandemic influenza. , 1996, Epidemiologic reviews.

[48]  B. Murphy,et al.  Human immune responses to influenza virus vaccines administered by systemic or mucosal routes. , 1995, Vaccine.

[49]  J. Oxford,et al.  An early humoral immune response in peripheral blood following parenteral inactivated influenza vaccination. , 1994, Vaccine.

[50]  W. Dupont,et al.  A randomized controlled trial of cold-adapted and inactivated vaccines for the prevention of influenza A disease. , 1994, The Journal of infectious diseases.