Live Attenuated versus Inactivated Influenza Vaccine in Infants and Young Children
Robert B. Belshe, M.D., Kathryn M. Edwards, M.D., Timo Vesikari, M.D., Steven V. Black, M.D., Robert E. Walker, M.D., Micki Hultquist, M.S., George Kemble, Ph.D., Edward M. Connor, M.D., for the CAIV-T Comparative Efficacy Study Group
ABSTRACT
Background Universal vaccination of children 6 to 59 months of age with trivalent inactivated influenza vaccine has recently been recommended by U.S. advisory bodies. To evaluate alternative vaccine approaches, we compared the safety and efficacy of intranasally administered live attenuated influenza vaccine with those of inactivated vaccine in infants and young children.
Methods Children 6 to 59 months of age, without a recent episode of wheezing illness or severe asthma, were randomly assigned in a 1:1 ratio to receive either cold-adapted trivalent live attenuated influenza vaccine (a refrigeration-stable formulation of live attenuated intranasally administered influenza vaccine) or trivalent inactivated vaccine in a double-blind manner. Influenza-like illness was monitored with cultures throughout the 2004–2005 influenza season.
Results Safety data were available for 8352 children, and 7852 children completed the study according to the protocol. There were 54.9% fewer cases of cultured-confirmed influenza in the group that received live attenuated vaccine than in the group that received inactivated vaccine (153 vs. 338 cases, P<0.001). The superior efficacy of live attenuated vaccine, as compared with inactivated vaccine, was observed for both antigenically well-matched and drifted viruses. Among previously unvaccinated children, wheezing within 42 days after the administration of dose 1 was more common with live attenuated vaccine than with inactivated vaccine, primarily among children 6 to 11 months of age; in this age group, 12 more episodes of wheezing were noted within 42 days after receipt of dose 1 among recipients of live attenuated vaccine (3.8%) than among recipients of inactivated vaccine (2.1%, P=0.076). Rates of hospitalization for any cause during the 180 days after vaccination were higher among the recipients of live attenuated vaccine who were 6 to 11 months of age (6.1%) than among the recipients of inactivated vaccine in this age group (2.6%, P=0.002).
Conclusions Among young children, live attenuated vaccine had significantly better efficacy than inactivated vaccine. An evaluation of the risks and benefits indicates that live attenuated vaccine should be a highly effective, safe vaccine for children 12 to 59 months of age who do not have a history of asthma or wheezing. (ClinicalTrials.gov number, NCT00128167 [ClinicalTrials.gov] .)
Source Information
From the Saint Louis University Health Sciences Center, St. Louis (R.B.B.); Vanderbilt University School of Medicine, Nashville (K.M.E.); University of Tampere Medical School, Tampere, Finland (T.V.); Kaiser Permanente Vaccine Study Center, Oakland, CA (S.V.B.); and MedImmune, Gaithersburg, MD (R.E.W., M.H., G.K., E.M.C.).
Address reprint requests to Dr. Belshe at the Division of Infectious Diseases and Immunology, Saint Louis University School of Medicine, 3635 Vista Ave. (FDT-8N), St. Louis, MO 63110, or at [email protected].
Full Text of this Article
This article has been cited by other articles:
* Khazeni, N., Bravata, D. M., Holty, J.-E. C., Uyeki, T. M., Stave, C. D., Gould, M. K. (2009). Systematic Review: Safety and Efficacy of Extended-Duration Antiviral Chemoprophylaxis Against Pandemic and Seasonal Influenza. ANN INTERN MED 151: 464-473 [Abstract] [Full Text]
* Basta, N. E., Chao, D. L., Halloran, M. E., Matrajt, L., Longini, I. M. Jr (2009). Strategies for Pandemic and Seasonal Influenza Vaccination of Schoolchildren in the United States. Am J Epidemiol 170: 679-686 [Abstract] [Full Text]
* Sexton, A., De Rose, R., Reece, J. C., Alcantara, S., Loh, L., Moffat, J. M., Laurie, K., Hurt, A., Doherty, P. C., Turner, S. J., Kent, S. J., Stambas, J. (2009). Evaluation of Recombinant Influenza Virus-Simian Immunodeficiency Virus Vaccines in Macaques. J. Virol. 83: 7619-7628 [Abstract] [Full Text]
* Lowen, A. C., Steel, J., Mubareka, S., Carnero, E., Garcia-Sastre, A., Palese, P. (2009). Blocking Interhost Transmission of Influenza Virus by Vaccination in the Guinea Pig Model. J. Virol. 83: 2803-2818 [Abstract] [Full Text]
* Weinstock, D. M., Zuccotti, G. (2009). The Evolution of Influenza Resistance and Treatment. JAMA 301: 1066-1069 [Full Text]
* Wang, Z., Tobler, S., Roayaei, J., Eick, A. (2009). Live Attenuated or Inactivated Influenza Vaccines and Medical Encounters for Respiratory Illnesses Among US Military Personnel. JAMA 301: 945-953 [Abstract] [Full Text]
* Li, C., Freedman, M. (2009). Seasonal Influenza: An Overview. The Journal of School Nursing 25: 4S-12S [Abstract] [Full Text]
* Basta, N. E., Halloran, M. E., Matrajt, L., Longini, I. M. Jr. (2008). Estimating Influenza Vaccine Efficacy From Challenge and Community-based Study Data. Am J Epidemiol 168: 1343-1352 [Abstract] [Full Text]
* Szilagyi, P. G., Fairbrother, G., Griffin, M. R., Hornung, R. W., Donauer, S., Morrow, A., Altaye, M., Zhu, Y., Ambrose, S., Edwards, K. M., Poehling, K. A., Lofthus, G., Holloway, M., Finelli, L., Iwane, M., Staat, M. A., for the New Vaccine Surveillance Network, (2008). Influenza Vaccine Effectiveness Among Children 6 to 59 Months of Age During 2 Influenza Seasons: A Case-Cohort Study. Arch Pediatr Adolesc Med 162: 943-951 [Abstract] [Full Text]
* Vasu, N., Ghaffari, G., Craig, E. T., Craig, T. J. (2008). Adverse events associated with intranasal influenza vaccine in the United States. Ther Adv Respir Dis 2: 193-198 [Abstract]
* Forrest, B. D., Pride, M. W., Dunning, A. J., Capeding, M. R. Z., Chotpitayasunondh, T., Tam, J. S., Rappaport, R., Eldridge, J. H., Gruber, W. C. (2008). Correlation of Cellular Immune Responses with Protection against Culture-Confirmed Influenza Virus in Young Children. CVI 15: 1042-1053 [Abstract] [Full Text]
* Poehling, K. A., Miller, E. K., Weinberg, G. A., Hall, C. B., Fairbrother, G. (2008). Influenza Virus and Acute Asthma in Children: In Reply. Pediatrics 121: 1080-1080 [Full Text]
* Committee on Infectious Diseases, (2008). Prevention of Influenza: Recommendations for Influenza Immunization of Children, 2007-2008. Pediatrics 121: e1016-e1031 [Abstract] [Full Text]
* Cross, A. S., Chen, W. H., Levine, M. M. (2008). A case for immunization against nosocomial infections. J. Leukoc. Biol. 83: 483-488 [Abstract] [Full Text]
* Nolan, T., Bernstein, D. I., Block, S. L., Hilty, M., Keyserling, H. L., Marchant, C., Marshall, H., Richmond, P., Yogev, R., Cordova, J., Cho, I., Mendelman, P. M., for the LAIV Study Group, (2008). Safety and Immunogenicity of Concurrent Administration of Live Attenuated Influenza Vaccine With Measles-Mumps-Rubella and Varicella Vaccines to Infants 12 to 15 Months of Age. Pediatrics 121: 508-516 [Abstract] [Full Text]
* Schmier, J., Li, S., King, J. C. Jr., Nichol, K., Mahadevia, P. J. (2008). Benefits And Costs Of Immunizing Children Against Influenza At School: An Economic Analysis Based On A Large-Cluster Controlled Clinical Trial. Health Aff (Millwood) 27: w96-w104 [Abstract] [Full Text]
* Vesikari, T., Karvonen, A., Smith, H. M., Dunning, A., Razmpour, A., Saville, M. K., Gruber, W. C., Forrest, B. D. (2008). Safety and Tolerability of Cold-Adapted Influenza Vaccine, Trivalent, in Infants Younger Than 6 Months of Age. Pediatrics 121: e568-e573 [Abstract] [Full Text]
* Tosh, P. K., Boyce, T. G., Poland, G. A. (2008). Flu Myths: Dispelling the Myths Associated With Live Attenuated Influenza Vaccine. Mayo Clin Proc. 83: 77-84 [Abstract] [Full Text]
* Block, S. L., Reisinger, K. S., Hultquist, M., Walker, R. E., for the CAIV-T Study Group, (2007). Comparative Immunogenicities of Frozen and Refrigerated Formulations of Live Attenuated Influenza Vaccine in Healthy Subjects. Antimicrob. Agents Chemother. 51: 4001-4008 [Abstract] [Full Text]
* (2007). Lucina. Arch. Dis. Child. 92: 658-658 [Full Text]
* Aldous, M. (2007). Efficacy and Safety of Live Attenuated Influenza Vaccine in Young Children. AAP Grand Rounds 17: 63-64 [Full Text]
* Cox, N. J., Bridges, C. B. (2007). Inactivated and Live Attenuated Influenza Vaccines in Young Children -- How Do They Compare?. NEJM 356: 729-731 [Full Text]
* (2007). Attenuated vs. Inactivated Flu Vaccine in Children: Benefits and Adverse Effects. JWatch Infect. Diseases 2007: 1-1 [Full Text]
* (2007). Flu Shots or Intranasal Flu Vaccine for Children?. JWatch Pediatrics 2007: 1-1 [Full Text]
Robert B. Belshe, M.D., Kathryn M. Edwards, M.D., Timo Vesikari, M.D., Steven V. Black, M.D., Robert E. Walker, M.D., Micki Hultquist, M.S., George Kemble, Ph.D., Edward M. Connor, M.D., for the CAIV-T Comparative Efficacy Study Group
ABSTRACT
Background Universal vaccination of children 6 to 59 months of age with trivalent inactivated influenza vaccine has recently been recommended by U.S. advisory bodies. To evaluate alternative vaccine approaches, we compared the safety and efficacy of intranasally administered live attenuated influenza vaccine with those of inactivated vaccine in infants and young children.
Methods Children 6 to 59 months of age, without a recent episode of wheezing illness or severe asthma, were randomly assigned in a 1:1 ratio to receive either cold-adapted trivalent live attenuated influenza vaccine (a refrigeration-stable formulation of live attenuated intranasally administered influenza vaccine) or trivalent inactivated vaccine in a double-blind manner. Influenza-like illness was monitored with cultures throughout the 2004–2005 influenza season.
Results Safety data were available for 8352 children, and 7852 children completed the study according to the protocol. There were 54.9% fewer cases of cultured-confirmed influenza in the group that received live attenuated vaccine than in the group that received inactivated vaccine (153 vs. 338 cases, P<0.001). The superior efficacy of live attenuated vaccine, as compared with inactivated vaccine, was observed for both antigenically well-matched and drifted viruses. Among previously unvaccinated children, wheezing within 42 days after the administration of dose 1 was more common with live attenuated vaccine than with inactivated vaccine, primarily among children 6 to 11 months of age; in this age group, 12 more episodes of wheezing were noted within 42 days after receipt of dose 1 among recipients of live attenuated vaccine (3.8%) than among recipients of inactivated vaccine (2.1%, P=0.076). Rates of hospitalization for any cause during the 180 days after vaccination were higher among the recipients of live attenuated vaccine who were 6 to 11 months of age (6.1%) than among the recipients of inactivated vaccine in this age group (2.6%, P=0.002).
Conclusions Among young children, live attenuated vaccine had significantly better efficacy than inactivated vaccine. An evaluation of the risks and benefits indicates that live attenuated vaccine should be a highly effective, safe vaccine for children 12 to 59 months of age who do not have a history of asthma or wheezing. (ClinicalTrials.gov number, NCT00128167 [ClinicalTrials.gov] .)
Source Information
From the Saint Louis University Health Sciences Center, St. Louis (R.B.B.); Vanderbilt University School of Medicine, Nashville (K.M.E.); University of Tampere Medical School, Tampere, Finland (T.V.); Kaiser Permanente Vaccine Study Center, Oakland, CA (S.V.B.); and MedImmune, Gaithersburg, MD (R.E.W., M.H., G.K., E.M.C.).
Address reprint requests to Dr. Belshe at the Division of Infectious Diseases and Immunology, Saint Louis University School of Medicine, 3635 Vista Ave. (FDT-8N), St. Louis, MO 63110, or at [email protected].
Full Text of this Article
This article has been cited by other articles:
* Khazeni, N., Bravata, D. M., Holty, J.-E. C., Uyeki, T. M., Stave, C. D., Gould, M. K. (2009). Systematic Review: Safety and Efficacy of Extended-Duration Antiviral Chemoprophylaxis Against Pandemic and Seasonal Influenza. ANN INTERN MED 151: 464-473 [Abstract] [Full Text]
* Basta, N. E., Chao, D. L., Halloran, M. E., Matrajt, L., Longini, I. M. Jr (2009). Strategies for Pandemic and Seasonal Influenza Vaccination of Schoolchildren in the United States. Am J Epidemiol 170: 679-686 [Abstract] [Full Text]
* Sexton, A., De Rose, R., Reece, J. C., Alcantara, S., Loh, L., Moffat, J. M., Laurie, K., Hurt, A., Doherty, P. C., Turner, S. J., Kent, S. J., Stambas, J. (2009). Evaluation of Recombinant Influenza Virus-Simian Immunodeficiency Virus Vaccines in Macaques. J. Virol. 83: 7619-7628 [Abstract] [Full Text]
* Lowen, A. C., Steel, J., Mubareka, S., Carnero, E., Garcia-Sastre, A., Palese, P. (2009). Blocking Interhost Transmission of Influenza Virus by Vaccination in the Guinea Pig Model. J. Virol. 83: 2803-2818 [Abstract] [Full Text]
* Weinstock, D. M., Zuccotti, G. (2009). The Evolution of Influenza Resistance and Treatment. JAMA 301: 1066-1069 [Full Text]
* Wang, Z., Tobler, S., Roayaei, J., Eick, A. (2009). Live Attenuated or Inactivated Influenza Vaccines and Medical Encounters for Respiratory Illnesses Among US Military Personnel. JAMA 301: 945-953 [Abstract] [Full Text]
* Li, C., Freedman, M. (2009). Seasonal Influenza: An Overview. The Journal of School Nursing 25: 4S-12S [Abstract] [Full Text]
* Basta, N. E., Halloran, M. E., Matrajt, L., Longini, I. M. Jr. (2008). Estimating Influenza Vaccine Efficacy From Challenge and Community-based Study Data. Am J Epidemiol 168: 1343-1352 [Abstract] [Full Text]
* Szilagyi, P. G., Fairbrother, G., Griffin, M. R., Hornung, R. W., Donauer, S., Morrow, A., Altaye, M., Zhu, Y., Ambrose, S., Edwards, K. M., Poehling, K. A., Lofthus, G., Holloway, M., Finelli, L., Iwane, M., Staat, M. A., for the New Vaccine Surveillance Network, (2008). Influenza Vaccine Effectiveness Among Children 6 to 59 Months of Age During 2 Influenza Seasons: A Case-Cohort Study. Arch Pediatr Adolesc Med 162: 943-951 [Abstract] [Full Text]
* Vasu, N., Ghaffari, G., Craig, E. T., Craig, T. J. (2008). Adverse events associated with intranasal influenza vaccine in the United States. Ther Adv Respir Dis 2: 193-198 [Abstract]
* Forrest, B. D., Pride, M. W., Dunning, A. J., Capeding, M. R. Z., Chotpitayasunondh, T., Tam, J. S., Rappaport, R., Eldridge, J. H., Gruber, W. C. (2008). Correlation of Cellular Immune Responses with Protection against Culture-Confirmed Influenza Virus in Young Children. CVI 15: 1042-1053 [Abstract] [Full Text]
* Poehling, K. A., Miller, E. K., Weinberg, G. A., Hall, C. B., Fairbrother, G. (2008). Influenza Virus and Acute Asthma in Children: In Reply. Pediatrics 121: 1080-1080 [Full Text]
* Committee on Infectious Diseases, (2008). Prevention of Influenza: Recommendations for Influenza Immunization of Children, 2007-2008. Pediatrics 121: e1016-e1031 [Abstract] [Full Text]
* Cross, A. S., Chen, W. H., Levine, M. M. (2008). A case for immunization against nosocomial infections. J. Leukoc. Biol. 83: 483-488 [Abstract] [Full Text]
* Nolan, T., Bernstein, D. I., Block, S. L., Hilty, M., Keyserling, H. L., Marchant, C., Marshall, H., Richmond, P., Yogev, R., Cordova, J., Cho, I., Mendelman, P. M., for the LAIV Study Group, (2008). Safety and Immunogenicity of Concurrent Administration of Live Attenuated Influenza Vaccine With Measles-Mumps-Rubella and Varicella Vaccines to Infants 12 to 15 Months of Age. Pediatrics 121: 508-516 [Abstract] [Full Text]
* Schmier, J., Li, S., King, J. C. Jr., Nichol, K., Mahadevia, P. J. (2008). Benefits And Costs Of Immunizing Children Against Influenza At School: An Economic Analysis Based On A Large-Cluster Controlled Clinical Trial. Health Aff (Millwood) 27: w96-w104 [Abstract] [Full Text]
* Vesikari, T., Karvonen, A., Smith, H. M., Dunning, A., Razmpour, A., Saville, M. K., Gruber, W. C., Forrest, B. D. (2008). Safety and Tolerability of Cold-Adapted Influenza Vaccine, Trivalent, in Infants Younger Than 6 Months of Age. Pediatrics 121: e568-e573 [Abstract] [Full Text]
* Tosh, P. K., Boyce, T. G., Poland, G. A. (2008). Flu Myths: Dispelling the Myths Associated With Live Attenuated Influenza Vaccine. Mayo Clin Proc. 83: 77-84 [Abstract] [Full Text]
* Block, S. L., Reisinger, K. S., Hultquist, M., Walker, R. E., for the CAIV-T Study Group, (2007). Comparative Immunogenicities of Frozen and Refrigerated Formulations of Live Attenuated Influenza Vaccine in Healthy Subjects. Antimicrob. Agents Chemother. 51: 4001-4008 [Abstract] [Full Text]
* (2007). Lucina. Arch. Dis. Child. 92: 658-658 [Full Text]
* Aldous, M. (2007). Efficacy and Safety of Live Attenuated Influenza Vaccine in Young Children. AAP Grand Rounds 17: 63-64 [Full Text]
* Cox, N. J., Bridges, C. B. (2007). Inactivated and Live Attenuated Influenza Vaccines in Young Children -- How Do They Compare?. NEJM 356: 729-731 [Full Text]
* (2007). Attenuated vs. Inactivated Flu Vaccine in Children: Benefits and Adverse Effects. JWatch Infect. Diseases 2007: 1-1 [Full Text]
* (2007). Flu Shots or Intranasal Flu Vaccine for Children?. JWatch Pediatrics 2007: 1-1 [Full Text]