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Hum Vaccin Immunother. 2015 Jul 15:0. [Epub ahead of print]
Safety and persistence of the humoral and cellular immune responses induced by two doses of an AS03-adjuvanted A(H1N1)pdm09 pandemic influenza vaccine administered to infants, children and adolescents: two open, uncontrolled studies.
Garcia-Sicilia J1, Ar?stegui J, Ome?aca F, Carmona A, Tejedor JC, Merino JM, Garc?a-Corbeira P, Walravens K, Bambure V, Moris P, Caplanusi A, Gillard P, Dieussaert I.
Author information
Abstract
In children, two AS03-adjuvanted A(H1N1)pdm09 vaccine doses given 21 days apart were previously shown to induce a high humoral immune response and to have an acceptable safety profile up to 42 days following the first vaccination. Here, we analysed the persistence data from two open-label studies, which assessed the safety, and humoral and cell-mediated immune responses induced by two doses of this vaccine. The first study was a phase II, randomised trial conducted in 104 children aged 6-35 months vaccinated with the A(H1N1)pdm09 vaccine containing 1.9 μg haemagglutinin antigen (HA) and AS03B (5.93 mg tocopherol) and the second study, a phase III, non-randomised trial conducted in 210 children and adolescents aged 3-17 years vaccinated with the A(H1N1)pdm09 vaccine containing 3.75 μg HA and AS03A (11.86 mg tocopherol). Approximately one year after the first dose, all children with available data were seropositive for haemagglutinin inhibition and neutralising antibody titres, but a decline in geometric mean antibody titres was noted. The vaccine induced a cell-mediated immune response in terms of antigen-specific CD4+ T-cells, which persisted up to one year post-vaccination. The vaccine did not raise any safety concern, though these trials were not designed to detect rare events. In conclusion, two doses of the AS03-adjuvanted A(H1N1)pdm09 vaccine at two different dosages had a clinically acceptable safety profile, and induced high and persistent humoral and cell-mediated immune responses in children aged 6-35 months and 3-17 years.
KEYWORDS:
AESI= adverse event of specific interest; AS03 adjuvant; AS03= tocopherol oil-in-water emulsion based adjuvant system; ATP= according to protocol; CHMP= Committee for Medicinal Products for Human Use; CI= confidence interval; CMI= cell-mediated immunity; GMFR= geometric mean fold rise; GMT= geometric mean titre; H1N1 pandemic vaccine; HA= haemagglutinin antigen; HI= haemagglutinin inhibition; IFN-γ= gamma interferon; IL-13= interleukin-13; IL-2= interleukin-2; MAE= medically attended event; PCR= polymerase chain reaction; SAE= serious adverse event; SCR= seroconversion rate; SPR= seroprotection rate; TH1= T helper 1; TH2= T helper 2; TNF-α= tumor necrosis factor alpha; VRR= vaccine response rate; WHO= World Health Organization; cell-mediated immunity; children; haemagglutinin inhibition; microneutralisation; pIMD= potential immune-mediated disease; persistence; safety
PMID: 26176592 [PubMed - as supplied by publisher]
Safety and persistence of the humoral and cellular immune responses induced by two doses of an AS03-adjuvanted A(H1N1)pdm09 pandemic influenza vaccine administered to infants, children and adolescents: two open, uncontrolled studies.
Garcia-Sicilia J1, Ar?stegui J, Ome?aca F, Carmona A, Tejedor JC, Merino JM, Garc?a-Corbeira P, Walravens K, Bambure V, Moris P, Caplanusi A, Gillard P, Dieussaert I.
Author information
Abstract
In children, two AS03-adjuvanted A(H1N1)pdm09 vaccine doses given 21 days apart were previously shown to induce a high humoral immune response and to have an acceptable safety profile up to 42 days following the first vaccination. Here, we analysed the persistence data from two open-label studies, which assessed the safety, and humoral and cell-mediated immune responses induced by two doses of this vaccine. The first study was a phase II, randomised trial conducted in 104 children aged 6-35 months vaccinated with the A(H1N1)pdm09 vaccine containing 1.9 μg haemagglutinin antigen (HA) and AS03B (5.93 mg tocopherol) and the second study, a phase III, non-randomised trial conducted in 210 children and adolescents aged 3-17 years vaccinated with the A(H1N1)pdm09 vaccine containing 3.75 μg HA and AS03A (11.86 mg tocopherol). Approximately one year after the first dose, all children with available data were seropositive for haemagglutinin inhibition and neutralising antibody titres, but a decline in geometric mean antibody titres was noted. The vaccine induced a cell-mediated immune response in terms of antigen-specific CD4+ T-cells, which persisted up to one year post-vaccination. The vaccine did not raise any safety concern, though these trials were not designed to detect rare events. In conclusion, two doses of the AS03-adjuvanted A(H1N1)pdm09 vaccine at two different dosages had a clinically acceptable safety profile, and induced high and persistent humoral and cell-mediated immune responses in children aged 6-35 months and 3-17 years.
KEYWORDS:
AESI= adverse event of specific interest; AS03 adjuvant; AS03= tocopherol oil-in-water emulsion based adjuvant system; ATP= according to protocol; CHMP= Committee for Medicinal Products for Human Use; CI= confidence interval; CMI= cell-mediated immunity; GMFR= geometric mean fold rise; GMT= geometric mean titre; H1N1 pandemic vaccine; HA= haemagglutinin antigen; HI= haemagglutinin inhibition; IFN-γ= gamma interferon; IL-13= interleukin-13; IL-2= interleukin-2; MAE= medically attended event; PCR= polymerase chain reaction; SAE= serious adverse event; SCR= seroconversion rate; SPR= seroprotection rate; TH1= T helper 1; TH2= T helper 2; TNF-α= tumor necrosis factor alpha; VRR= vaccine response rate; WHO= World Health Organization; cell-mediated immunity; children; haemagglutinin inhibition; microneutralisation; pIMD= potential immune-mediated disease; persistence; safety
PMID: 26176592 [PubMed - as supplied by publisher]