Clinical and Immune Responses to Inactivated Influenza A(H1N1)pdm09 Vaccine in Children

Abstract

Background As the influenza AH1N1 pandemic emerged in 2009, children were found to experience high morbidity and mortality and were prioritized for vaccination. This multicenter, randomized, double-blind, age-stratified trial assessed the safety and immunogenicity of inactivated influenza A(H1N1)pdm09 vaccine in healthy children aged 6 months to 17 years. Methods Children received two doses of approximately 15 μg or 30 μg hemagglutin antigen 21 days apart. Reactogenicity was assessed for 8 days after each dose, adverse events through day 42, and serious adverse events or new-onset chronic illnesses through day 201. Serum hemagglutination inhibition (HAI) titers were measured on days 0 (pre-vaccination), 8, 21, 29, and 42. Results A total of 583 children received the first dose and 571 received the second dose of vaccine. Vaccinations were generally well-tolerated and no related serious adverse events were observed. The 15 μg dosage elicited a seroprotective HAI (≥1:40) in 20%, 47%, and 93% of children in the 6-35 month, 3-9 year, and 10-17 year age strata 21 days after dose 1 and in 78%, 82%, and 98% of children 21 days after dose 2, respectively. The 30 μg vaccine dosage induced similar responses. Conclusions The inactivated influenza A(H1N1)pdm09 vaccine exhibited a favorable safety profile at both dosage levels. While a single 15 or 30 μg dose induced seroprotective antibody responses in most 10-17 year olds, younger children required 2 doses, even when receiving dosages 4-6 fold higher than recommended. Well-tolerated vaccines are needed that induce immunity after a single dose for use in young children during influenza pandemics.

Overcoming the Neonatal Limitations of Inducing Germinal Centers through Liposome-Based Adjuvants Including C-Type Lectin Agonists Trehalose Dibehenate or Curdlan

“…However, maternal antibodies wane rapidly after birth. Between 6 and 25 months of life, trivalent influenza vaccines (TIV) have limited immunogenicity and protective efficacy ( 2 , 3 ), which may be enhanced in part by MF59 ® adjuvantation ( 4 ). In contrast, influenza vaccines for infants younger than 6 months are lacking: TIV showed poor efficacy ( 3 ) and the live attenuated intranasal vaccine appeared too reactogenic in this age group ( 5 ).…”

Long-term seroprotective response of trivalent seasonal influenza vaccine in HIV-infected children, regardless of immunogenicity before immunisation

“…This was similar to another study in which HIV-infected children had a high seroprotection rate of 75% after inoculation with the inactivated split-virion AS03-adjuvanted pandemic H1N1(2009) vaccine, 14 while another previous study showed that the seroprotection rates of the inactivated influenza A (H1N1) pdm 2009 vaccine in healthy children were 78 to 98% at 21 days. 27 A previous study in response to TIV reported that 73% of healthy children exhibited protective responses. 28 In contrast, a similar previous study showed the proportion of seroconversion for H1N1, H3N2 and influenza B strains in HIV-infected children were 47.5, 50.0 and 40.0%, respectively.…”

The CTA1-DD adjuvant strongly potentiates follicular dendritic cell function and germinal center formation, which results in improved neonatal immunization

“…Earlier attempts at vaccinating against influenza in these age groups have been quite discouraging and associated with significant adverse reactions. [71][72][73][74] However, these studies did not explore the potential of mucosal vaccination, but other vaccine studies have evaluated the use of oral priming in neonatal Macaque and Pig models against Simian immunodeficiency virus and rotavirus, albeit using live attenuated vaccines, with promising results. 75,76 As oral priming is more effective for stimulating immune protection against enteric infections we also intend to test neonatal vaccination against rotavirus infections, using a CTA1-VP6-DD fusion protein.…”