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Vienna, Austria

Barrett P.N.,Biomedical Research Center | Portsmouth D.,Biomedical Research Center | Ehrlich H.J.,Global RandD
Expert Review of Vaccines

Several subtypes of influenza A viruses with pandemic potential are endemic in bird populations throughout Asia, Africa and the Middle East, and evidence suggests that these viruses are adapting to the mammalian host. As emphasized by the high mortality rate of humans infected with H5N1 viruses, this situation presents a substantial risk to global human health. The Vero cell culture platform has been used to develop whole-virus influenza vaccines that provide broad cross-clade protection against viruses with pandemic potential, at low antigen doses, without the requirement for adjuvantation. The safety and immunogenicity of these vaccines has been demonstrated in studies with more than 10,000 individuals, including healthy adult and elderly subjects, children and various risk groups. These Vero cell-derived vaccines are licensed for prepandemic and pandemic use. The Vero platform is also being explored to develop next-generation live-attenuated and recombinant vaccines. © 2013 2013 Expert Reviews Ltd. Source

Hohenadl C.,Vaccine RandD | Wodal W.,Vaccine RandD | Kerschbaum A.,Vaccine RandD | Fritz R.,Vaccine RandD | And 8 more authors.
Virology Journal

Background: Convalescent plasma and fractionated immunoglobulins have been suggested as prophylactic or therapeutic interventions during an influenza pandemic. Findings. Intravenous immunoglobulin (IVIG) preparations manufactured from human plasma collected before the 2009 H1N1 influenza pandemic, and post-pandemic hyperimmune (H)-IVIG preparations were characterized with respect to hemagglutination inhibition (HI), microneutralization (MN) and neuraminidase-inhibiting (NAi) antibody titers against pandemic H1N1 (pH1N1) and seasonal H1N1 (sH1N1) viruses. The protective efficacy of the IVIG and H-IVIG preparations was evaluated in a SCID mouse challenge model.Substantial levels of HI, MN and NAi antibodies against pH1N1 (GMTs 1:45, 1:204 and 1: 727, respectively) and sH1N1 (GMTs 1:688, 1:4,946 and 1:312, respectively) were present in pre-pandemic IVIG preparations. In post-pandemic H-IVIG preparations, HI, MN and NAi antibody GMTs against pH1N1 were 1:1,280, 1:11,404 and 1:2,488 (28-, 56- and 3.4-fold enriched), respectively, compared to pre-pandemic IVIG preparations (p < 0.001). Post-pandemic H-IVIG (HI titer 1:1,280) provided complete protection from lethality of SCID mice against pH1N1 challenge (100% of mice survived for 29 days post-challenge). Pre-pandemic IVIG (HI titer 1:70) did not provide significant protection against pH1N1 challenge (50% of mice survived 29 days post-challenge compared to 40% survival in the buffer control group). There was a highly significant correlation between circulating in vivo HI and MN antibody titers and survival (p < 0001). Conclusion: The substantial enrichment of HA- and NA-specific antibodies in H-IVIG and the efficacious protection of SCID mice against challenge with pH1N1 suggests H-IVIG as a promising intervention against pandemic influenza for immunocompromised patients and other risk groups. © 2014 Hohenadl et al.; licensee BioMed Central Ltd. Source

Tambyah P.A.,National University Hospital Singapore | Wilder-Smith A.,National University Hospital Singapore | Pavlova B.G.,Global RandD | Barrett P.N.,Global RandD | And 10 more authors.

A successful vaccine development strategy for areas with clustered H5N1 events requires conduct of vaccine trials in potentially non-naïve subjects and evaluation of post-vaccination responsiveness. An open-label, randomized, phase I/II study therefore assessed the immunogenicity and safety of two different dose levels of an inactivated, non-adjuvanted, whole virus clade 2.1 (A/Indonesia/05/2005) H5N1 Vero cell-derived influenza vaccine in healthy adults (21-45 years) from a region where the virus has been circulating (Hong Kong) as well as Singapore. Subjects (N=110) were randomized 1:1 to receive two vaccinations with either 3.75μg or 7.5μg H5N1 haemagglutinin antigen 21 days apart. Safety, immunogenicity (microneutralization [MN] and single radial haemolysis [SRH] at baseline and post-vaccination) and cross-reactivity against a heterologous clade 1 strain (A/Vietnam/1203/2004) of the vaccine were assessed. Pre-existing immunity to the vaccine strain was 14% which is higher than previously reported for these regions. Two vaccinations with either vaccine formulation induced high seroprotection rates (MN titre ≥ 1:20) against the vaccine strain A/Indonesia/05/2005: 82.7% and 86.5% in the 3.75μg and 7.5μg dose groups. Seroconversion rates and fold increase exceeded the CPMP criterion of >40% and >2.5 for MN and SRH in both dose groups after the second vaccination, while the seroprotection rate in the 7.5μg dose group determined by SRH was only marginally lower (69.2%) than the CPMP criterion of >70%. Thus, 11 of 12 CHMP criteria were fulfilled. A cross-reactive antibody response against the heterologous A/Vietnam/1203/2004 strain was demonstrated after the second vaccination (>21% by MN and ≥25% by SRH). Persistence of antibodies against the vaccine strain was also demonstrated 6 months after the first vaccination, indicating that a booster vaccination would be effective in those who have received two priming doses. No serious adverse events were reported. The H5N1 influenza vaccine against clade 2.1 strain A/Indonesia/05/2005 was well tolerated and immunogenic after two vaccinations, and induced a cross-neutralizing antibody response, with no dose effect. © 2011 Elsevier Ltd. Source

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