Correspondence
Responses to 2009 H1N1 Vaccine in Children 3 to 17 Years of Age
N Engl J Med 2010; 362:370-372January 28, 2010
- Article
To the Editor:
The current 2009 pandemic influenza A (H1N1) virus is associated with substantial morbidity in children, with 45% of hospitalizations occurring in patients under 18 years of age.1 One possible reason for this trend is a lack of preexisting immunity against the 2009 H1N1 virus among children.2 Experience with other pandemic vaccines has suggested that two doses of vaccine for children and adults would be needed to meet the licensure criteria of the Center for Biologics Evaluation and Research (CBER).3 According to these criteria, the lower bound of the two-sided 95% confidence interval should meet or exceed 40% in subjects achieving seroconversion on hemagglutination-inhibition (HI) assay and should meet or exceed 70% in subjects with an HI antibody titer of 1:40 or more. Data from recent studies4,5 have shown that in adults one 15-μg dose of influenza A/California/2009 (H1N1) vaccine (CSL Biotherapies and Novartis) met licensing criteria.
In a randomized, single-center study in Costa Rica, we tested various doses of egg-based 2009 H1N1 vaccine (Novartis) in subjects ranging in age from 3 to 64 years, including 194 subjects between the ages of 3 and 8 years and 196 subjects between the ages of 9 and 17 years (ClinicalTrials.gov number, NCT00973700). The vaccines were formulated with or without the adjuvant MF59 that was used in a European licensed influenza vaccine (Novartis). The study was approved by the ethics committee of the Universidad de Ciencias Médicas. Parents of all subjects provided written informed consent.
Subjects in the two age groups, who were more than 99% Hispanic, were randomly assigned (in a 2:3:2 ratio) to receive one 7.5-μg hemagglutinin dose with adjuvant or either one or two 15-μg doses without adjuvant. After vaccination, local and systemic events were generally mild to moderate. Less than 4% of subjects reported having severe events in any of the vaccine or age groups, and no vaccine-related serious adverse events were reported (for details, see the Supplementary Appendix, available with the full text of this letter at NEJM.org). By day 22, all three vaccine regimens had elicited increases in HI titers in the two age groups (Figure 1Figure 1
Immunogenicity of Three Regimens of 2009 H1N1 Vaccine, According to Age Group.). Rates of seroconversion were greater than 70% in all age and vaccine groups. After a single dose of vaccine, all three vaccine regimens met the CBER criterion for the HI antibody titer among subjects 9 to 17 years of age, but only the 7.5-μg dose of vaccine with adjuvant met this criterion among children 3 to 8 years of age.These preliminary data support the use of one 15-μg dose of 2009 H1N1 vaccine without adjuvant in children between the ages of 9 and 17 years. However, in children 3 to 8 years of age, only the 7.5-μg dose of 2009 H1N1 vaccine with adjuvant met both the immunogenicity criteria after one dose, and the criterion for the HI antibody titer was not met by either one or two 15-μg doses without adjuvant. The use of adjuvant may provide a rapid immune response at a lower hemagglutinin dose than that required in vaccine without adjuvant. This may increase the availability of vaccine for rapid immunization in young children, an age group that is at substantial risk for hospitalization associated with influenza.
Adriano Arguedas, M.D.
Carolina Soley, M.D.
Instituto de Atención Pediátrica, San José, Costa RicaKelly Lindert, M.D.
Novartis Vaccines and Diagnostics, Cambridge, MA
kelly.lindert@novartis. com Financial and other disclosures provided by the authors are available with the full text of this letter at NEJM.org.
This letter (10.1056/NEJMc0909988) was published on December 30, 2009, at NEJM.org.
5 References1
Jain S ,Kamimoto L ,Bramley AM , et al. Hospitalized patients with 2009 H1N1 influenza in the United States, April-June 2009. N Engl J Med 2009;361:1935-1944
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Medline3
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4
Greenberg ME ,Lai MH ,Hartel GF , et al. Response to a monovalent 2009 influenza A (H1N1) vaccine. N Engl J Med 2009;361:2405-2413
Full Text | Web of Science | Medline5
Clark TW ,Pareek M ,Hoschler K , et al. Trial of 2009 influenza A (H1N1) monovalent MF59-adjuvanted vaccine. N Engl J Med 2009;361:2424-2435
Full Text | Web of Science | Medline
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