Phase II, randomized, open, controlled study of AS03-adjuvanted H5N1 pre-pandemic influenza vaccine in children aged 3 to 9 years: follow-up of safety and immunogenicity persistence at 24 months post-vaccination.

BACKGROUND: An AS03-adjuvanted H5N1 influenza vaccine elicited broad and persistent immune responses with an acceptable safety profile up to 6 months following the first vaccination in children aged 3-9 years. METHODS: In this follow-up of the Phase II study, we report immunogenicity persistence and safety at 24 months post-vaccination in children aged 3-9 years. The randomized, open-label study assessed two doses of H5N1 A/Vietnam/1194/2004 influenza vaccine (1·9 µg or 3·75 µg hemagglutinin antigen) formulated with AS03A or AS03B (11·89 mg or 5·93 mg tocopherol, respectively). Control groups received seasonal trivalent influenza vaccine. Safety was assessed prospectively and included potential immune-mediated diseases (pIMDs). Immunogenicity was assessed by hemagglutination-inhibition assay 12 and 24 months after vaccination; cross-reactivity and cell-mediated responses were also assessed. (NCT00502593). RESULTS: The safety population included 405 children. Over 24 months, five events fulfilled the criteria for pIMDs, of which four occurred in H5N1 vaccine recipients, including uveitis (n = 1) and autoimmune hepatitis (n = 1), which were considered to be vaccine-related. Overall, safety profiles of the vaccines were clinically acceptable. Humoral immune responses at 12 and 24 months were reduced versus those observed after the second dose of vaccine, although still within the range of those observed after the first dose. Persistence of cell-mediated immunity was strong, and CD4(+) T cells with a TH 1 profile were observed. CONCLUSIONS: Two doses of an AS03-adjuvanted H5N1 influenza vaccine in children showed low but persistent humoral immune responses and a strong persistence of cell-mediated immunity, with clinically acceptable safety profiles up to 24 months following first vaccination.

Immunogenicity and Safety of H5N1 A/Vietnam/1194/2004 (Clade 1) AS03-adjuvanted prepandemic candidate influenza vaccines in children aged 3 to 9 years: a phase ii, randomized, open, controlled study.

BACKGROUND: The development of vaccines against pandemic influenza viruses for use in children is a public health priority. METHODS: In this phase II, randomized, open study, the immunogenicity and reactogenicity of H5N1 A/Vietnam/1194/2004 (NIBRG-14) (clade 1) prepandemic influenza vaccine were assessed in children aged 3 to 5 and 6 to 9 years. Children were randomized to receive 2 doses, given 21 days apart, of A/Vietnam/1194/2004 vaccine containing 1.9 microg or 3.75 microg hemagglutinin antigen (HA), adjuvanted with a tocopherol-based oil-in-water emulsion (AS03) containing 11.86 mg (AS03(A)) or 5.93 mg (AS03(B)) tocopherol. Control groups received 2 doses of trivalent influenza vaccine (TIV). Humoral immune responses, reactogenicity, and safety were the primary outcome measures; cross-reactivity and cell-mediated responses were also assessed (NCT00502593). RESULTS: Between 49 and 51 children in each age stratum (aged 3-5 and 6-9 years) received H5N1 vaccine, and between 17 and 18 children in each age stratum received TIV. After the second dose, recipients of H5N1 vaccine (1.9 microg HA/AS03(B), 3.75 microg HA/AS03(B), and 3.75 microg HA/AS03(A)) achieved humoral antibody titers against the vaccine-homologous strain, which fulfilled the United States influenza vaccines licensure criteria for immunogenicity. With the exception of 1 child, there were no H5N1 immune responses in children who received TIV. The most frequent injection-site event was pain in all groups, and the H5N1 vaccine had a clinically acceptable reactogenicity and safety profile. Exploratory analyses in children aged 3 to 5 years indicated that the induction of CD4 T-cell responses polarized in favor of a T-helper 1 profile. CONCLUSIONS: The results showed that 2 doses of AS03-adjuvanted H5N1 influenza vaccine at antigen-sparing doses of 1.9 microg or 3.75 microg HA elicited broad and persistent immune responses with acceptable reactogenicity, and without safety concerns, in children aged 3 to 9 years.

Pauci-immune extracapillary glomerulonephritis and atheromatous embolization.

Renal atheroembolic disease presents several multisystemic signs and symptoms that may resemble the clinical signs of vasculitis. A few cases of renal atheroembolism associated with antineutrophil cytoplasmic antibodies (ANCA) have been described. We report the first case, to our knowledge, of a patient with cholesterol microemboli who also developed extracapillary glomerulonephritis in the presence of perinuclear ANCA (p-ANCA) with anti-myeloperoxidase ANCA. The patient had long-term follow-up of renal function after treatment with prednisone and cyclophosphamide.