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Otfried Kistner - One of the best experts on this subject based on the ideXlab platform.
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Cell culture Vero Cell derived whole virus non adjuvanted h5n1 influenza vaccine induces long lasting cross reactive memory immune response homologous or heterologous booster response following two dose or single dose priming
Vaccine, 2012Co-Authors: Maikel V W Van Der Velden, Otfried Kistner, Gerald Aichinger, Sandor Fritsch, Markus Muller, Eva Maria Pollabauer, Alexandra Lowbaselli, Karima Benamara, Markus Zeitlinger, Herwig KollaritschAbstract:Abstract Background Influenza pandemic preparedness involves priming of the population with pre-pandemic vaccines. Such vaccines should be well tolerated and induce a long-lasting immunological memory that can effectively be boosted with a single dose of pandemic vaccine once available. The presented studies assessed different prime-boost regimens with a Vero Cell-derived whole virus non-adjuvanted H5N1 vaccine. Methods In one study, 281 healthy adult (18–59 years) and 280 elderly (≥60 years) subjects received two vaccinations, 21 days apart, with Vero Cell-derived whole virus non-adjuvanted H5N1 vaccine (7.5 μg HA antigen A/Vietnam/1203/2004) followed by a 6, 12–15, or 24 month booster (7.5 or 3.75 μg A/Indonesia/05/2005 or A/Vietnam/1203/2004). In the other study, 230 healthy adults (18–59 years) received single dose priming (7.5 μg A/Vietnam/1203/2004) followed by a 12 month booster (7.5 or 3.75 μg A/Indonesia/05/2005). Antibody responses were assessed by microneutralization (MN) and single radial hemolysis (SRH) assay. Vaccine safety was assessed throughout. Results Two dose priming was equally immunogenic in adults and the elderly: >72% of subjects in each population achieved MN titers ≥1:20 after the second vaccination. Booster vaccinations at 6, 12–15, and 24 months induced substantial antibody increases to both strains: after a 7.5 μg A/Indonesia/05/2005 booster, 93–95% of adults and 72–84% of the elderly achieved MN titers ≥ 1:20 against this strain. Homologous and heterologous booster responses were higher in the 7.5 μg dose group than in the 3.75 μg dose group. Booster responses following single dose priming were similar; a 7.5 μg booster dose induced homologous MN titers ≥1:20 in 93% of subjects. Conclusions A Vero Cell derived whole virus non-adjuvanted H5N1 influenza vaccine is well tolerated and induces long-lasting cross-clade immunological memory that can be effectively boosted 1–2 years after two dose or single dose priming, supporting its suitability for pre-pandemic vaccination.
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a Vero Cell derived whole virus h5n1 vaccine effectively induces neuraminidase inhibiting antibodies
The Journal of Infectious Diseases, 2012Co-Authors: Richard Fritz, Noel P Barrett, Hartmut J Ehrlich, Otfried Kistner, Keith M Howard, Christine Hohenadl, Nicolas Sabarth, Stefan Kiermayr, Thomas R KreilAbstract:: A Vero Cell-derived whole-virus H5N1 influenza vaccine has been shown to induce neutralizing antibodies directed against the hemagglutinin (HA) protein of diverse H5N1 strains in animal studies and clinical trials. However, neuraminidase-inhibiting (NAi) antibodies can reduce viral spread and may be of particular importance in the event of an H5N1 pandemic, where immunity due to HA antibodies is likely absent in the general population. Here we demonstrate the effective induction of NAi antibody titers after H5N1 vaccination in humans. In contrast to the immune response directed toward HA, a single vaccine dose induced a strong NAi response that was not significantly boosted by a second dose, most probably due to priming by previous vaccination or infection with seasonal influenza viruses. After 2 immunizations, seroconversion rates based on antibody titers against HA and NA were similar, indicating the induction of equally strong immune responses against both proteins by this H5N1 vaccine.
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efficacy safety and immunogenicity of a Vero Cell culture derived trivalent influenza vaccine a multicentre double blind randomised placebo controlled trial
The Lancet, 2011Co-Authors: Noel P Barrett, Otfried Kistner, Gerald Aichinger, Sandor Fritsch, Gregory Berezuk, Mary Kate Hart, Wael Elamin, Hartmut J EhrlichAbstract:Summary Background The use of Cell-culture technologies for the manufacture of influenza vaccines might contribute to improved strain selection and robust vaccine supplies. We investigated the safety, immunogenicity, and protective efficacy of a Vero-Cell-culture-derived influenza vaccine, and assessed the correlation between vaccine efficacy and haemagglutination inhibition antibody titre. Methods In a double-blind, placebo-controlled, phase 3 trial undertaken in 36 centres in the USA, healthy adults (aged 18–49 years) were randomly assigned in a 1:1 ratio to one injection of either placebo or Vero-Cell-culture-derived influenza vaccine during the 2008–09 season. Randomisation was done in blocks by use of the random number generator algorithm, and participants were allocated by use of a centralised telephone system. The primary objective was the efficacy of the vaccine in preventing Cell-culture-confirmed influenza infection with viruses that were antigenically matched to one of the vaccine strains. Analysis was by intention to treat. The study is registered with ClinicalTrials.gov, number NCT00566345. Findings 7250 participants were randomly assigned to vaccine (n=3626) and placebo (n=3624). 7236 were analysed for the primary outcome (n=3619 and n=3617, respectively). Overall protective efficacy for antigenically matched influenza infection was 78·5% (95% CI 60·8–88·2). The vaccine was well tolerated with no treatment-related serious adverse events. Adverse events were mainly mild and transient. An HI titre of at least 1:15 provided a reliable correlate of Cell-culture-derived influenza vaccine-induced protection; no additional benefit was noted with titres greater than 1:30. Interpretation The data indicate that existing correlates of protection afforded with egg-derived seasonal influenza vaccines also apply to this vaccine. Funding Federal (US Government) funds from the Office for Preparedness and Response, Biomedical Advanced Research and Development Authority, under contract to DynPort Vaccine Company.
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Vero Cell platform in vaccine production moving towards Cell culture based viral vaccines
Expert Review of Vaccines, 2009Co-Authors: Noel P Barrett, Otfried Kistner, Wolfgang Mundt, Keith M HowardAbstract:The development of Cell culture systems for virus propagation has led to major advances in virus vaccine development. Primary and diploid Cell culture systems are now being replaced by the use of continuous Cell lines (CCLs). These substrates are gaining increasing acceptance from regulatory authorities as improved screening technologies remove fears regarding their potential oncogenic properties. The Vero Cell line is the most widely accepted CCL by regulatory authorities and has been used for over 30 years for the production of polio and rabies virus vaccines. The recent licensure of a Vero Cell-derived live virus vaccine (ACAM2000, smallpox vaccine) has coincided with an explosion in the development of a range of new viral vaccines, ranging from live-attenuated pediatric vaccines against rotavirus infections to inactivated whole-virus vaccines against H5N1 pandemic influenza. These developments have illustrated the value of this Cell culture platform in the rapid development of vaccines against a range...
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humoral and Cell mediated immunity to Vero Cell derived influenza vaccine
Vaccine, 2000Co-Authors: Peter Bruhl, Astrid Kerschbaum, Otfried Kistner, Noel Barrett, Friedrich Dorner, Marijan GerencerAbstract:Abstract A candidate trivalent influenza whole virus vaccine produced in a continuous mammalian Cell line (Vero), and analogous commercially available egg-derived vaccines, were compared for their ability to induce humoral and Cell-mediated immunity in Balb/c mice. Substantial haemagglutination-inhibition titre and high levels of influenza virus-specific IgG were found in all groups of immunized mice, irrespective of the vaccine formulation. The IgG responses were predominantly of IgG1 and IgG2a/2b isotypes. Virus-specific secretory IgA antibodies were detected only in mice immunized intranasally with a live virus, derived either from Vero Cells or eggs. T-Cell proliferative responses and T-helper 1 type cytokine release was significantly higher in mice immunized with Vero Cell-derived influenza vaccine compared to egg-derived vaccine formulations. We have demonstrated that the immunogenicity of the trivalent Vero Cell-derived whole influenza virus vaccine was comparable to that of the equivalent egg-derived vaccine, with respect to humoral immune response and was superior with respect to Cellular response.
Noel P Barrett - One of the best experts on this subject based on the ideXlab platform.
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Vero Cell culture derived pandemic influenza vaccines preclinical and clinical development
Expert Review of Vaccines, 2013Co-Authors: Noel P Barrett, Daniel Portsmouth, Hartmut J EhrlichAbstract: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.
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safety and immunogenicity of two different doses of a Vero Cell derived whole virus clade 2 h5n1 a indonesia 05 2005 influenza vaccine
Vaccine, 2012Co-Authors: Paul A Tambyah, Noel P Barrett, Gerald Aichinger, Sandor Fritsch, Annelies Wildersmith, Borislava G Pavlova, Helen M L Oh, Kwokyung Yuen, Alexandra Loewbaselli, Maikel V W Van Der VeldenAbstract:Abstract A successful vaccine development strategy for areas with clustered H5N1 events requires conduct of vaccine trials in potentially non-naive 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 3.75 μg or 7.5 μg 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 3.75 μg and 7.5 μg 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 7.5 μg 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.
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a Vero Cell derived whole virus h5n1 vaccine effectively induces neuraminidase inhibiting antibodies
The Journal of Infectious Diseases, 2012Co-Authors: Richard Fritz, Noel P Barrett, Hartmut J Ehrlich, Otfried Kistner, Keith M Howard, Christine Hohenadl, Nicolas Sabarth, Stefan Kiermayr, Thomas R KreilAbstract:: A Vero Cell-derived whole-virus H5N1 influenza vaccine has been shown to induce neutralizing antibodies directed against the hemagglutinin (HA) protein of diverse H5N1 strains in animal studies and clinical trials. However, neuraminidase-inhibiting (NAi) antibodies can reduce viral spread and may be of particular importance in the event of an H5N1 pandemic, where immunity due to HA antibodies is likely absent in the general population. Here we demonstrate the effective induction of NAi antibody titers after H5N1 vaccination in humans. In contrast to the immune response directed toward HA, a single vaccine dose induced a strong NAi response that was not significantly boosted by a second dose, most probably due to priming by previous vaccination or infection with seasonal influenza viruses. After 2 immunizations, seroconversion rates based on antibody titers against HA and NA were similar, indicating the induction of equally strong immune responses against both proteins by this H5N1 vaccine.
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efficacy safety and immunogenicity of a Vero Cell culture derived trivalent influenza vaccine a multicentre double blind randomised placebo controlled trial
The Lancet, 2011Co-Authors: Noel P Barrett, Otfried Kistner, Gerald Aichinger, Sandor Fritsch, Gregory Berezuk, Mary Kate Hart, Wael Elamin, Hartmut J EhrlichAbstract:Summary Background The use of Cell-culture technologies for the manufacture of influenza vaccines might contribute to improved strain selection and robust vaccine supplies. We investigated the safety, immunogenicity, and protective efficacy of a Vero-Cell-culture-derived influenza vaccine, and assessed the correlation between vaccine efficacy and haemagglutination inhibition antibody titre. Methods In a double-blind, placebo-controlled, phase 3 trial undertaken in 36 centres in the USA, healthy adults (aged 18–49 years) were randomly assigned in a 1:1 ratio to one injection of either placebo or Vero-Cell-culture-derived influenza vaccine during the 2008–09 season. Randomisation was done in blocks by use of the random number generator algorithm, and participants were allocated by use of a centralised telephone system. The primary objective was the efficacy of the vaccine in preventing Cell-culture-confirmed influenza infection with viruses that were antigenically matched to one of the vaccine strains. Analysis was by intention to treat. The study is registered with ClinicalTrials.gov, number NCT00566345. Findings 7250 participants were randomly assigned to vaccine (n=3626) and placebo (n=3624). 7236 were analysed for the primary outcome (n=3619 and n=3617, respectively). Overall protective efficacy for antigenically matched influenza infection was 78·5% (95% CI 60·8–88·2). The vaccine was well tolerated with no treatment-related serious adverse events. Adverse events were mainly mild and transient. An HI titre of at least 1:15 provided a reliable correlate of Cell-culture-derived influenza vaccine-induced protection; no additional benefit was noted with titres greater than 1:30. Interpretation The data indicate that existing correlates of protection afforded with egg-derived seasonal influenza vaccines also apply to this vaccine. Funding Federal (US Government) funds from the Office for Preparedness and Response, Biomedical Advanced Research and Development Authority, under contract to DynPort Vaccine Company.
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Vero Cell platform in vaccine production moving towards Cell culture based viral vaccines
Expert Review of Vaccines, 2009Co-Authors: Noel P Barrett, Otfried Kistner, Wolfgang Mundt, Keith M HowardAbstract:The development of Cell culture systems for virus propagation has led to major advances in virus vaccine development. Primary and diploid Cell culture systems are now being replaced by the use of continuous Cell lines (CCLs). These substrates are gaining increasing acceptance from regulatory authorities as improved screening technologies remove fears regarding their potential oncogenic properties. The Vero Cell line is the most widely accepted CCL by regulatory authorities and has been used for over 30 years for the production of polio and rabies virus vaccines. The recent licensure of a Vero Cell-derived live virus vaccine (ACAM2000, smallpox vaccine) has coincided with an explosion in the development of a range of new viral vaccines, ranging from live-attenuated pediatric vaccines against rotavirus infections to inactivated whole-virus vaccines against H5N1 pandemic influenza. These developments have illustrated the value of this Cell culture platform in the rapid development of vaccines against a range...
Hartmut J Ehrlich - One of the best experts on this subject based on the ideXlab platform.
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Vero Cell culture derived pandemic influenza vaccines preclinical and clinical development
Expert Review of Vaccines, 2013Co-Authors: Noel P Barrett, Daniel Portsmouth, Hartmut J EhrlichAbstract: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.
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a Vero Cell derived whole virus h5n1 vaccine effectively induces neuraminidase inhibiting antibodies
The Journal of Infectious Diseases, 2012Co-Authors: Richard Fritz, Noel P Barrett, Hartmut J Ehrlich, Otfried Kistner, Keith M Howard, Christine Hohenadl, Nicolas Sabarth, Stefan Kiermayr, Thomas R KreilAbstract:: A Vero Cell-derived whole-virus H5N1 influenza vaccine has been shown to induce neutralizing antibodies directed against the hemagglutinin (HA) protein of diverse H5N1 strains in animal studies and clinical trials. However, neuraminidase-inhibiting (NAi) antibodies can reduce viral spread and may be of particular importance in the event of an H5N1 pandemic, where immunity due to HA antibodies is likely absent in the general population. Here we demonstrate the effective induction of NAi antibody titers after H5N1 vaccination in humans. In contrast to the immune response directed toward HA, a single vaccine dose induced a strong NAi response that was not significantly boosted by a second dose, most probably due to priming by previous vaccination or infection with seasonal influenza viruses. After 2 immunizations, seroconversion rates based on antibody titers against HA and NA were similar, indicating the induction of equally strong immune responses against both proteins by this H5N1 vaccine.
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safety and immunogenicity of an inactivated whole virus Vero Cell derived ross river virus vaccine a randomized trial
Vaccine, 2011Co-Authors: Gerald Aichinger, Hartmut J Ehrlich, John Aaskov, Sandor Fritsch, Christiane Thomasser, Wolfgang Draxler, Michael Wolzt, Markus Muller, Fritz Pinl, Pierre Van DammeAbstract:Abstract Background Ross River virus (RRV) is endemic in Australia and several South Pacific Islands. Approximately 5000 cases of RRV disease, which is characterized by debilitating polyarthritis, are recorded each year in Australia. This study describes the first clinical trial of a candidate RRV vaccine. Methods An inactivated whole-virus Vero Cell-derived RRV vaccine was tested in 382 healthy, RRV-naive adults in a phase 1/2 dose-escalation study at ten sites in Austria, Belgium and The Netherlands. Subjects were equally randomized to receive 1.25 μg, 2.5 μg, 5 μg, or 10 μg aluminum hydroxide-adjuvanted or non-adjuvanted RRV vaccine, with a second dose after three weeks and a booster at six months. Vaccine immunogenicity was determined by measurements of serum IgG and neutralizing antibody titers. Vaccine tolerability and safety were monitored over the entire study period. Results The optimal vaccine formulation was the adjuvanted 2.5 μg dose, as calculated using a repeated mixed model analysis of covariance comparing log-transformed RRV-specific IgG titers between different dose groups. Geometric means of RRV-specific serum antibodies measured 21 days after the third vaccination with the 2.5 μg adjuvanted formulation were 520.9 (90% CI 377.2–719.4) as determined by IgG ELISA and 119.9 (82.6–173.9) as determined by virus neutralization assay, resulting in seropositivity rates of 92.9% (82.6–98.0) and 92.7% (82.2–98.0), respectively. All vaccine formulations and doses were well tolerated after the first, second and third vaccination. Conclusions The adjuvanted, inactivated whole-virus Vero Cell-derived Ross River virus vaccine is highly immunogenic in RRV-naive adults and well tolerated at all dose levels.
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efficacy safety and immunogenicity of a Vero Cell culture derived trivalent influenza vaccine a multicentre double blind randomised placebo controlled trial
The Lancet, 2011Co-Authors: Noel P Barrett, Otfried Kistner, Gerald Aichinger, Sandor Fritsch, Gregory Berezuk, Mary Kate Hart, Wael Elamin, Hartmut J EhrlichAbstract:Summary Background The use of Cell-culture technologies for the manufacture of influenza vaccines might contribute to improved strain selection and robust vaccine supplies. We investigated the safety, immunogenicity, and protective efficacy of a Vero-Cell-culture-derived influenza vaccine, and assessed the correlation between vaccine efficacy and haemagglutination inhibition antibody titre. Methods In a double-blind, placebo-controlled, phase 3 trial undertaken in 36 centres in the USA, healthy adults (aged 18–49 years) were randomly assigned in a 1:1 ratio to one injection of either placebo or Vero-Cell-culture-derived influenza vaccine during the 2008–09 season. Randomisation was done in blocks by use of the random number generator algorithm, and participants were allocated by use of a centralised telephone system. The primary objective was the efficacy of the vaccine in preventing Cell-culture-confirmed influenza infection with viruses that were antigenically matched to one of the vaccine strains. Analysis was by intention to treat. The study is registered with ClinicalTrials.gov, number NCT00566345. Findings 7250 participants were randomly assigned to vaccine (n=3626) and placebo (n=3624). 7236 were analysed for the primary outcome (n=3619 and n=3617, respectively). Overall protective efficacy for antigenically matched influenza infection was 78·5% (95% CI 60·8–88·2). The vaccine was well tolerated with no treatment-related serious adverse events. Adverse events were mainly mild and transient. An HI titre of at least 1:15 provided a reliable correlate of Cell-culture-derived influenza vaccine-induced protection; no additional benefit was noted with titres greater than 1:30. Interpretation The data indicate that existing correlates of protection afforded with egg-derived seasonal influenza vaccines also apply to this vaccine. Funding Federal (US Government) funds from the Office for Preparedness and Response, Biomedical Advanced Research and Development Authority, under contract to DynPort Vaccine Company.
Elisabeth Schuller - One of the best experts on this subject based on the ideXlab platform.
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safety profile of the Vero Cell derived japanese encephalitis virus jev vaccine ixiaro
Vaccine, 2011Co-Authors: Elisabeth Schuller, Anton Klingler, Katrin Dubischarkastner, Shailesh Dewasthaly, Zsuzsanna MullerAbstract:Abstract Japanese encephalitis (JE) is the most common cause for viral encephalitis in Asia and can be effectively prevented by vaccination. IXIARO ® is a Vero Cell-derived, inactivated JE virus vaccine which has been licensed and distributed in the US, Europe, Canada, Hongkong, Israel, and distributed in Australia under the trade name JESPECT ® . This paper reviews the safety profile of IXIARO ® in the first 12 months after licensure and discusses the observed profile in the context of clinical trial results for IXIARO ® and post-marketing safety data for JE-VAX ® . The clinical safety profile is derived from a pooled analysis including safety data from 10 phase III trials in 4043 subjects who received at least one IXIARO ® vaccination and were followed-up for up to 3 years after the primary immunization. Local and systemic tolerability of IXIARO ® was similar to an earlier safety analysis at the time of licensure of the vaccine. In post-marketing AE reports, the system organ classes affected following vaccination with IXIARO ® were similar to the previously observed clinical trial profile. No serious allergic reactions were observed in the 12-month post-marketing period. This comprehensive safety review confirms the good safety profile of IXIARO ® in clinical and post-marketing use.
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safety analysis of a Vero Cell culture derived japanese encephalitis vaccine ixiaro ic51 in 6 months of follow up
Vaccine, 2010Co-Authors: Katrin Dubischarkastner, Anton Klingler, Bernd Jilma, Astrid Kaltenboeck, Elisabeth SchullerAbstract:Abstract Japanese encephalitis (JE) is the most common viral encephalitis in Asia. IXIARO ® is a Vero Cell-derived, inactivated JE virus vaccine which has recently been approved in the US, Europe, Canada and Australia (trade name JESPECT). This overview of the safety and tolerability of IXIARO ® , for 6 months after the first vaccination in 7 Phase III trials, includes: 3558 subjects with at least one IXIARO ® vaccination, 435 subjects with a JE-VAX ® (manufactured by BIKEN, distributed by Sanofi Pasteur) vaccination, and 657 with phosphate-buffered saline solution with 0.1% Al(OH) 3 (PBS + Alum) control vaccination. The percentage of subjects reporting solicited local adverse events (AEs) with IXIARO ® (54%) was similar to PBS + Alum vaccination (56%) as were solicited systemic adverse events (40% IXIARO ® ; 40% PBS + Alum vaccination). JE-VAX ® showed a higher frequency of subjects with solicited local adverse events (61%) but a slightly lower frequency of subjects with solicited systemic adverse events (36%). The frequency of subjects with any solicited and unsolicited AE with IXIARO ® (64%) was also similar to PBS + Alum vaccination (61%) and JE-VAX ® (64%); as for subjects with serious AEs (1% IXIARO ® ; 2% PBS + Alum vaccination, 1% JE-VAX ® ). No serious allergic reactions were observed in any group. This safety analysis indicates that IXIARO ® has a favorable safety profile, comparable to PBS + Alum control vaccination and appears to have a better local tolerability profile than JE-VAX ® .
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long term immunogenicity of the new Vero Cell derived inactivated japanese encephalitis virus vaccine ic51 six and 12 month results of a multicenter follow up phase 3 study
Vaccine, 2008Co-Authors: Elisabeth Schuller, Herwig Kollaritsch, Bernd Jilma, Victor Voicu, G Golor, A Kaltenbock, Christoph Klade, Erich TauberAbstract:Japanese encephalitis (JE) is the most common viral encephalitis in Asia. IC51 is a new Vero Cell-derived, inactivated JE virus vaccine with non-inferior immunogenicity (after 2 months) compared to the US-licensed vaccine JE-VAX® (mouse brain-derived, inactivated) and with a more convenient (two injections instead of three) intramuscular dose schedule. Adult subjects from two studies were followed-up for comparative immunogenicity (JE-VAX®) at 6 months and long-term immunogenicity of IC51 alone at 12 months. At 6 months, immunogenicity was higher with IC51 (seroconversion rate [SCR] 95%; geometric mean titer [GMT] 84) than with JE-VAX® (SCR 74%; GMT 34). At 12 months, the SCR was 83% and the GMT (41) remained above the protective titer of 1:10. Most people immunized with IC51 will have protective neutralizing antibody levels for at least a year.
Gerald Aichinger - One of the best experts on this subject based on the ideXlab platform.
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Cell culture Vero Cell derived whole virus non adjuvanted h5n1 influenza vaccine induces long lasting cross reactive memory immune response homologous or heterologous booster response following two dose or single dose priming
Vaccine, 2012Co-Authors: Maikel V W Van Der Velden, Otfried Kistner, Gerald Aichinger, Sandor Fritsch, Markus Muller, Eva Maria Pollabauer, Alexandra Lowbaselli, Karima Benamara, Markus Zeitlinger, Herwig KollaritschAbstract:Abstract Background Influenza pandemic preparedness involves priming of the population with pre-pandemic vaccines. Such vaccines should be well tolerated and induce a long-lasting immunological memory that can effectively be boosted with a single dose of pandemic vaccine once available. The presented studies assessed different prime-boost regimens with a Vero Cell-derived whole virus non-adjuvanted H5N1 vaccine. Methods In one study, 281 healthy adult (18–59 years) and 280 elderly (≥60 years) subjects received two vaccinations, 21 days apart, with Vero Cell-derived whole virus non-adjuvanted H5N1 vaccine (7.5 μg HA antigen A/Vietnam/1203/2004) followed by a 6, 12–15, or 24 month booster (7.5 or 3.75 μg A/Indonesia/05/2005 or A/Vietnam/1203/2004). In the other study, 230 healthy adults (18–59 years) received single dose priming (7.5 μg A/Vietnam/1203/2004) followed by a 12 month booster (7.5 or 3.75 μg A/Indonesia/05/2005). Antibody responses were assessed by microneutralization (MN) and single radial hemolysis (SRH) assay. Vaccine safety was assessed throughout. Results Two dose priming was equally immunogenic in adults and the elderly: >72% of subjects in each population achieved MN titers ≥1:20 after the second vaccination. Booster vaccinations at 6, 12–15, and 24 months induced substantial antibody increases to both strains: after a 7.5 μg A/Indonesia/05/2005 booster, 93–95% of adults and 72–84% of the elderly achieved MN titers ≥ 1:20 against this strain. Homologous and heterologous booster responses were higher in the 7.5 μg dose group than in the 3.75 μg dose group. Booster responses following single dose priming were similar; a 7.5 μg booster dose induced homologous MN titers ≥1:20 in 93% of subjects. Conclusions A Vero Cell derived whole virus non-adjuvanted H5N1 influenza vaccine is well tolerated and induces long-lasting cross-clade immunological memory that can be effectively boosted 1–2 years after two dose or single dose priming, supporting its suitability for pre-pandemic vaccination.
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safety and immunogenicity of two different doses of a Vero Cell derived whole virus clade 2 h5n1 a indonesia 05 2005 influenza vaccine
Vaccine, 2012Co-Authors: Paul A Tambyah, Noel P Barrett, Gerald Aichinger, Sandor Fritsch, Annelies Wildersmith, Borislava G Pavlova, Helen M L Oh, Kwokyung Yuen, Alexandra Loewbaselli, Maikel V W Van Der VeldenAbstract:Abstract A successful vaccine development strategy for areas with clustered H5N1 events requires conduct of vaccine trials in potentially non-naive 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 3.75 μg or 7.5 μg 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 3.75 μg and 7.5 μg 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 7.5 μg 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.
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safety and immunogenicity of an inactivated whole virus Vero Cell derived ross river virus vaccine a randomized trial
Vaccine, 2011Co-Authors: Gerald Aichinger, Hartmut J Ehrlich, John Aaskov, Sandor Fritsch, Christiane Thomasser, Wolfgang Draxler, Michael Wolzt, Markus Muller, Fritz Pinl, Pierre Van DammeAbstract:Abstract Background Ross River virus (RRV) is endemic in Australia and several South Pacific Islands. Approximately 5000 cases of RRV disease, which is characterized by debilitating polyarthritis, are recorded each year in Australia. This study describes the first clinical trial of a candidate RRV vaccine. Methods An inactivated whole-virus Vero Cell-derived RRV vaccine was tested in 382 healthy, RRV-naive adults in a phase 1/2 dose-escalation study at ten sites in Austria, Belgium and The Netherlands. Subjects were equally randomized to receive 1.25 μg, 2.5 μg, 5 μg, or 10 μg aluminum hydroxide-adjuvanted or non-adjuvanted RRV vaccine, with a second dose after three weeks and a booster at six months. Vaccine immunogenicity was determined by measurements of serum IgG and neutralizing antibody titers. Vaccine tolerability and safety were monitored over the entire study period. Results The optimal vaccine formulation was the adjuvanted 2.5 μg dose, as calculated using a repeated mixed model analysis of covariance comparing log-transformed RRV-specific IgG titers between different dose groups. Geometric means of RRV-specific serum antibodies measured 21 days after the third vaccination with the 2.5 μg adjuvanted formulation were 520.9 (90% CI 377.2–719.4) as determined by IgG ELISA and 119.9 (82.6–173.9) as determined by virus neutralization assay, resulting in seropositivity rates of 92.9% (82.6–98.0) and 92.7% (82.2–98.0), respectively. All vaccine formulations and doses were well tolerated after the first, second and third vaccination. Conclusions The adjuvanted, inactivated whole-virus Vero Cell-derived Ross River virus vaccine is highly immunogenic in RRV-naive adults and well tolerated at all dose levels.
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efficacy safety and immunogenicity of a Vero Cell culture derived trivalent influenza vaccine a multicentre double blind randomised placebo controlled trial
The Lancet, 2011Co-Authors: Noel P Barrett, Otfried Kistner, Gerald Aichinger, Sandor Fritsch, Gregory Berezuk, Mary Kate Hart, Wael Elamin, Hartmut J EhrlichAbstract:Summary Background The use of Cell-culture technologies for the manufacture of influenza vaccines might contribute to improved strain selection and robust vaccine supplies. We investigated the safety, immunogenicity, and protective efficacy of a Vero-Cell-culture-derived influenza vaccine, and assessed the correlation between vaccine efficacy and haemagglutination inhibition antibody titre. Methods In a double-blind, placebo-controlled, phase 3 trial undertaken in 36 centres in the USA, healthy adults (aged 18–49 years) were randomly assigned in a 1:1 ratio to one injection of either placebo or Vero-Cell-culture-derived influenza vaccine during the 2008–09 season. Randomisation was done in blocks by use of the random number generator algorithm, and participants were allocated by use of a centralised telephone system. The primary objective was the efficacy of the vaccine in preventing Cell-culture-confirmed influenza infection with viruses that were antigenically matched to one of the vaccine strains. Analysis was by intention to treat. The study is registered with ClinicalTrials.gov, number NCT00566345. Findings 7250 participants were randomly assigned to vaccine (n=3626) and placebo (n=3624). 7236 were analysed for the primary outcome (n=3619 and n=3617, respectively). Overall protective efficacy for antigenically matched influenza infection was 78·5% (95% CI 60·8–88·2). The vaccine was well tolerated with no treatment-related serious adverse events. Adverse events were mainly mild and transient. An HI titre of at least 1:15 provided a reliable correlate of Cell-culture-derived influenza vaccine-induced protection; no additional benefit was noted with titres greater than 1:30. Interpretation The data indicate that existing correlates of protection afforded with egg-derived seasonal influenza vaccines also apply to this vaccine. Funding Federal (US Government) funds from the Office for Preparedness and Response, Biomedical Advanced Research and Development Authority, under contract to DynPort Vaccine Company.
