tetano
Editor, Senior Moderator
Influenza Vaccine in Young Children
N Engl J Med 2012; 366:383-384January 26, 2012
Article
To the Editor:
Vesikari et al. (Oct. 13 issue)1 report an efficacy of 89% for a trivalent inactivated vaccine with an oil-in-water adjuvant (ATIV) in children 6 to 71 months of age against vaccine-matched strains. However, the efficacy of the trivalent inactivated vaccine without adjuvant (TIV) in the control group was lower than expected overall (45% vs. an expected 60%) and negligible (2%) among children 6 to 23 months of age. The TIV used in year 2, when 95% of the confirmed influenza cases occurred, was manufactured by GlaxoSmithKline. This TIV formulation was immunologically inferior to the Sanofi Pasteur TIV in a study involving children 6 to 59 months of age: strain-specific antibody titers were inferior and 48 to 63% lower among children 6 to 35 months of age and were noninferior but still 5 to 23% lower among children 36 to 59 months of age.2 These data may explain the low efficacy of TIV in the study by Vesikari et al. As noted by the authors, live attenuated influenza vaccine has been shown to have high efficacy in children as compared with placebo and TIV (manufactured by Sanofi Pasteur).3-5
Christopher S. Ambrose, M.D.
MedImmune, Gaithersburg, MD
ambrosec@medimmune.com
Robert B. Belshe, M.D.
Saint Louis University Medical Center, St. Louis, MO
Dr. Ambrose reports being an employee of MedImmune, the manufacturer of the live attenuated influenza vaccine. Dr. Belshe reports serving as a board member of Vivaldi Biosciences, receiving consulting fees from GlaxoSmithKline, receiving consulting and lecture fees from MedImmune, and receiving lecture fees from Merck.
No other potential conflict of interest relevant to this letter was reported.
5 References
To the Editor:
The study by Vesikari and colleagues shows greater immunogenicity and efficacy for the MF59-adjuvant influenza vaccine, as compared with a conventional dose of the nonadjuvant inactivated vaccine, in young children. However, the dose of the nonadjuvant vaccine may be critical for its efficacy in this age group. In our recent cohort study with virologically confirmed outcomes, the use of 0.5-ml (instead of 0.25-ml) doses for children under the age of 36 months showed a 79% vaccine effectiveness against matched strains of influenza and an overall effectiveness of 66% against any strains of influenza, even in children under the age of 2 years.1 In another recent study,2 the higher dose significantly increased children's antibody responses without any increase in reactogenicity. Because young children are known to have a relatively poor response to nonadjuvant influenza vaccines, it does not make much sense to give them vaccine doses that are lower than those used for children with an increased response. Further research into the effectiveness of doses of nonadjuvant vaccines that are higher than traditional doses for young children seems warranted.
Terho Heikkinen, M.D., Ph.D.
Santtu Heinonen, M.D.
Turku University Hospital, Turku, Finland
terho.heikkinen@utu.fi
Dr. Heikkinen reports receiving consulting fees from GlaxoSmithKline and Abbott/Solvay and consulting fees and honoraria from Novartis and AstraZeneca/MedImmune.
No other potential conflict of interest relevant to this letter was reported.
2 References
Author/Editor Response
We were unaware of differences between the TIVs cited by Ambrose and Belshe when our study began. However, in a previous study comparing MF59-ATIV and Sanofi Pasteur TIV (Vaxigrip) in children 6 to 35 months of age, we showed that the ATIV was also significantly more immunogenic for all three viral subtypes than the TIV.1 We disagree that the efficacy of 43% (95% confidence interval [CI], 15 to 61) for TIV in children under the age of 72 months in our trial was inordinately low. One meta-analysis showed no TIV studies in children 2 to 17 years of age with a design that was sufficiently rigorous to be included, and another meta-analysis concluded that TIV had a 59% efficacy (95% CI, 41 to 71) in healthy children under the age of 16 years, with no efficacy in those 6 to 24 months of age.2,3
We agree with Heikkinen and Heinonen that the appropriate TIV dose may not be reflected in current licensed pediatric indications. In their study, the vaccine effectiveness of 0.5 ml of TIV was 66% (95% CI, 29 to 84) against all circulating influenza strains in children under the age of 36 months. This finding falls between the efficacies of 43% (95% CI, 15 to 61) for TIV and of 86% (95% CI, 74 to 93) for ATIV in our study, in which 0.25-ml doses were used in children under the age of 72 months.
Timo Vesikari, M.D.
University of Tampere Medical School, Tampere, Finland
timo.vesikari@uta.fi
Theodore F. Tsai, M.D.
Novartis Vaccines, Cambridge, MA
Since publication of their article, the authors report no further potential conflict of interest.
http://www.ncbi.nlm.nih.gov/pubmed/22276840
N Engl J Med 2012; 366:383-384January 26, 2012
Article
To the Editor:
Vesikari et al. (Oct. 13 issue)1 report an efficacy of 89% for a trivalent inactivated vaccine with an oil-in-water adjuvant (ATIV) in children 6 to 71 months of age against vaccine-matched strains. However, the efficacy of the trivalent inactivated vaccine without adjuvant (TIV) in the control group was lower than expected overall (45% vs. an expected 60%) and negligible (2%) among children 6 to 23 months of age. The TIV used in year 2, when 95% of the confirmed influenza cases occurred, was manufactured by GlaxoSmithKline. This TIV formulation was immunologically inferior to the Sanofi Pasteur TIV in a study involving children 6 to 59 months of age: strain-specific antibody titers were inferior and 48 to 63% lower among children 6 to 35 months of age and were noninferior but still 5 to 23% lower among children 36 to 59 months of age.2 These data may explain the low efficacy of TIV in the study by Vesikari et al. As noted by the authors, live attenuated influenza vaccine has been shown to have high efficacy in children as compared with placebo and TIV (manufactured by Sanofi Pasteur).3-5
Christopher S. Ambrose, M.D.
MedImmune, Gaithersburg, MD
ambrosec@medimmune.com
Robert B. Belshe, M.D.
Saint Louis University Medical Center, St. Louis, MO
Dr. Ambrose reports being an employee of MedImmune, the manufacturer of the live attenuated influenza vaccine. Dr. Belshe reports serving as a board member of Vivaldi Biosciences, receiving consulting fees from GlaxoSmithKline, receiving consulting and lecture fees from MedImmune, and receiving lecture fees from Merck.
No other potential conflict of interest relevant to this letter was reported.
5 References
To the Editor:
The study by Vesikari and colleagues shows greater immunogenicity and efficacy for the MF59-adjuvant influenza vaccine, as compared with a conventional dose of the nonadjuvant inactivated vaccine, in young children. However, the dose of the nonadjuvant vaccine may be critical for its efficacy in this age group. In our recent cohort study with virologically confirmed outcomes, the use of 0.5-ml (instead of 0.25-ml) doses for children under the age of 36 months showed a 79% vaccine effectiveness against matched strains of influenza and an overall effectiveness of 66% against any strains of influenza, even in children under the age of 2 years.1 In another recent study,2 the higher dose significantly increased children's antibody responses without any increase in reactogenicity. Because young children are known to have a relatively poor response to nonadjuvant influenza vaccines, it does not make much sense to give them vaccine doses that are lower than those used for children with an increased response. Further research into the effectiveness of doses of nonadjuvant vaccines that are higher than traditional doses for young children seems warranted.
Terho Heikkinen, M.D., Ph.D.
Santtu Heinonen, M.D.
Turku University Hospital, Turku, Finland
terho.heikkinen@utu.fi
Dr. Heikkinen reports receiving consulting fees from GlaxoSmithKline and Abbott/Solvay and consulting fees and honoraria from Novartis and AstraZeneca/MedImmune.
No other potential conflict of interest relevant to this letter was reported.
2 References
Author/Editor Response
We were unaware of differences between the TIVs cited by Ambrose and Belshe when our study began. However, in a previous study comparing MF59-ATIV and Sanofi Pasteur TIV (Vaxigrip) in children 6 to 35 months of age, we showed that the ATIV was also significantly more immunogenic for all three viral subtypes than the TIV.1 We disagree that the efficacy of 43% (95% confidence interval [CI], 15 to 61) for TIV in children under the age of 72 months in our trial was inordinately low. One meta-analysis showed no TIV studies in children 2 to 17 years of age with a design that was sufficiently rigorous to be included, and another meta-analysis concluded that TIV had a 59% efficacy (95% CI, 41 to 71) in healthy children under the age of 16 years, with no efficacy in those 6 to 24 months of age.2,3
We agree with Heikkinen and Heinonen that the appropriate TIV dose may not be reflected in current licensed pediatric indications. In their study, the vaccine effectiveness of 0.5 ml of TIV was 66% (95% CI, 29 to 84) against all circulating influenza strains in children under the age of 36 months. This finding falls between the efficacies of 43% (95% CI, 15 to 61) for TIV and of 86% (95% CI, 74 to 93) for ATIV in our study, in which 0.25-ml doses were used in children under the age of 72 months.
Timo Vesikari, M.D.
University of Tampere Medical School, Tampere, Finland
timo.vesikari@uta.fi
Theodore F. Tsai, M.D.
Novartis Vaccines, Cambridge, MA
Since publication of their article, the authors report no further potential conflict of interest.
http://www.ncbi.nlm.nih.gov/pubmed/22276840