Safety and immunogenicity of an MF59®-adjuvanted A/H1N1 pandemic influenza vaccine in children from three to seventeen years of age

Abstract

a b s t r a c tObjectives: This study was designed to identify the optimal dose of an MF59® -adjuvanted, monovalent, A/H1N1 influenza vaccine in healthy paediatric subjects. Methods: Subjects aged 3-8 years (n = 194) and 9-17 years (n = 160) were randomized to receive two primary doses of A/H1N1 vaccine containing either 3.75 g antigen with half a standard dose of MF59 adjuvant, 7.5 g antigen with a full dose of MF59, or (children 3-8 years only), a non-adjuvanted 15 g formulation. A booster dose of MF59-adjuvanted seasonal influenza vaccine including homologous A/H1N1 strain was given one year after priming. Immunogenicity was assessed by haemagglutination inhibition (HI) and microneutralization assays. Vaccine safety was assessed throughout the study (up to 18 months). Results: A single priming dose of either MF59-adjuvanted formulation was sufficient to meet the European licensure criteria for pandemic influenza vaccines (HI titres ≥1:40 > 70%; seroconversion > 40%; and GMR > 2.5). Two non-adjuvanted vaccine doses were required to meet the same licensure criteria. After first and second doses, percentage of subjects with HI titres ≥1:40 were between 97% and 100% in the adjuvanted vaccine groups compared with 68% and 91% in the non-adjuvanted group, respectively. Postvaccination seroconversion rates ranged from 91% to 98% in adjuvanted groups and were 68% (first dose) and 98% (second dose) in the non-adjuvanted group. HI titres ≥1:330 after primary doses were achieved in 69% to 90% in adjuvanted groups compared with 41% in the non-adjuvanted group. Long-term antibody persistence after priming and a robust antibody response to booster immunization were observed in all vaccination groups. All A/H1N1 vaccine formulations were generally well tolerated. No vaccine-related serious adverse events occurred, and no subjects were withdrawn from the study due to an adverse event.Conclusions: An MF59-adjuvanted influenza vaccine containing 3.75 g of A/H1N1 antigen was well tolerated and sufficiently immunogenic to meet all the European licensure criteria after a single dose in healthy children 3-17 years old.

Immunogenicity of trivalent influenza vaccines in patients with chronic kidney disease undergoing hemodialysis: MF59-adjuvanted versus non-adjuvanted vaccines

“…19 Furthermore, the safety of the MF59-aIIV has been well described in children. 20 However, the safety profiles of 2 trivalent influenza vaccines were not assessed in this study.…”

Adjuvants Enhance the Induction of Germinal Center and Antibody Secreting Cells in Spleen and Their Persistence in Bone Marrow of Neonatal Mice

“…mmCT is a novel, non-toxic multiple-mutant of cholera toxin (CT) (33) that in addition to increasing IgG and IgA Ab responses to co-administered antigen and strong IFN-γ and IL-17A T cell responses in mice (34), it has been shown to promote human Th17 responses (35) through activation of the classical NF-κB pathway of monocytes (36). MF59, a squalene-based oil-in-water emulsion, was well tolerated and enhanced protective efficacy of influenza vaccination in infants and young children (37), meeting all the European licensure criteria (38) and has been licensed for use in children from 6 months with seasonal influenza vaccine (23). IC31, which combines two immunomodulatory compounds; an antibacterial peptide KLK (11-mer cationic peptide KLKL 5 KLK) and a TLR9 agonist, a synthetic oligodeoxynucleotide (ODN1a) without a CpG motif, has been shown to rapidly enhance protective humoral responses in neonates when combined with Pnc1-TT (39).…”

Emerging Influenza Strains in the Last Two Decades: A Threat of a New Pandemic?

“…The results showed that 59% of participants reached seroconversion after two lowest doses of antigen vaccine with MF59 adjuvant while without adjuvant the minimum antibody response has been reached by the highest antigen dosage [ 69 ]. The previous experience with H5N1 and H1N1 pandemic split vaccines shows the advantage of the MF59 adjuvant able to induce good immune response in a broad population with a low formulation dosage [ 70 , 71 , 72 ].…”