Pre-vaccination immunity and immune responses to a cell culture-derived whole-virus H1N1 vaccine are similar to a seasonal influenza vaccine

Ehrlich, Hartmut J.; Müller, Markus; Kollaritsch, Herwig; Pinl, Fritz; Schmitt, Bernhard; Zeitlinger, Markus; Loew-Baselli, Alexandra; Kreil, Thomas R.; Kistner, Otfried; Portsmouth, Daniel; Fritsch, Sandor; Maritsch, Friedrich; Aichinger, Gerald; Pavlova, Borislava G.; Barrett, Perry

doi:10.1016/j.vaccine.2012.03.061

Cited by 17 publications

(15 citation statements)

References 39 publications

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“…No vaccine-related serious AEs were reported, and the majority of the adverse reactions were rated as mild, consistent with the safety profile of the Vero-derived whole-virus H5N1 and H1N1 vaccines previously reported in clinical trials in healthy adults (7,11,38). The rates of injection site reactions were lower at the lower dose levels of 3.75 and 7.5 g than those at the 15-, 30-, and 45-g-dose levels.…”

Section: Discussionsupporting

confidence: 82%

“…The enzyme-linked immunosorbent assay (ELISA)-based MN assay is based on the assay originally developed for serological evaluation of H5N1 vaccines (37) and subsequently widely used for the evaluation of pandemic H1N1 vaccines (38)(39)(40)(41). In brief, duplicates of heat-inactivated serum samples were serially diluted with phosphate-buffered saline (PBS) in 2-fold steps, starting at a 1:5 dilution.…”

Section: Methodsmentioning

confidence: 99%

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Phase I/II Randomized Double-Blind Study of the Safety and Immunogenicity of a Nonadjuvanted Vero Cell Culture-Derived Whole-Virus H9N2 Influenza Vaccine in Healthy Adults

Aichinger

Grohmann-Izay

Velden

et al. 2014

Clin. Vaccine Immunol.

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dStudies on candidate pandemic vaccines against avian influenza viruses have focused on H5N1, but viruses of other subtypes, such as A/H9N2, are also considered to have pandemic potential. We investigated the safety and immunogenicity of two immunizations with one of five different antigen doses (ranging from 3.75 to 45 g of hemagglutinin antigen) of a nonadjuvanted whole-virus G9 lineage H9N2 influenza virus vaccine in healthy adults aged 18 to 49 years. The antibody responses were measured by hemagglutination inhibition (HI), microneutralization (MN), and single radial hemolysis (SRH) assays. To investigate a hypothesis that previous exposure to H2N2 viruses in subjects born in or before 1968 might prime for more robust antibody responses to H9N2 vaccination than that in subjects born after 1968, a post hoc age-stratified analysis of antibody responses was done. Both vaccinations in all dose groups were safe and well tolerated. No vaccine-related serious adverse events were reported, and the majority of the adverse reactions were rated as mild. The rates of injection site reactions were lower in the 3.75-g-and 7.5-g-dose groups than those in the higher-dose groups; the rates of systemic reactions were similar across all dose groups. The seroprotection rates among the different dose groups 21 days after the second immunization ranged from 52.8% to 88.9% as measured by HI assay, from 88.7% to 98.1% or 82.7% to 96.2% as measured by MN assay (MN titer cutoffs, 1:40 and 1:80, respectively), and from 94.2% to 100% as measured by SRH assay. Higher antibody responses were not induced in subjects born in or before 1968. These data indicate that a nonadjuvanted whole-virus H9N2 vaccine is well tolerated and immunogenic in healthy adults. (This study has been registered at ClinicalTrials.gov under registration no. NCT01320696.) A number of avian influenza virus subtypes have caused zoonotic infections in humans, including those of subtypes H5N1 (1), H9N2 (2), and, most recently, H7N9 (3) and H10N8 (4). Because the human population is largely immunologically naive to such viruses, there are concerns that a pandemic situation might occur if any of these viruses gains the capacity for efficient human-to-human transmission. The development of candidate pandemic vaccines to counter the threat of a pandemic resulting from avian influenza viruses is thus an important part of global pandemic preparedness programs (5, 6). To date, this effort has been concentrated largely on the development of candidate pandemic vaccines based on influenza viruses of the H5N1 subtype. A number of clinical studies have demonstrated whole-virus inactivated H5N1 vaccines to be immunogenic in adult, elderly, and pediatric populations without a requirement for adjuvantation (7-11). In the present study, we extend the clinical investigation of nonadjuvanted whole-virus avian influenza vaccines to include a vaccine against the H9N2 influenza virus subtype, which is enzootic in poultry across the Middle East and Asia and is considered to have pandemic po...

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Section: Discussionsupporting

confidence: 82%

Section: Methodsmentioning

confidence: 99%

Phase I/II Randomized Double-Blind Study of the Safety and Immunogenicity of a Nonadjuvanted Vero Cell Culture-Derived Whole-Virus H9N2 Influenza Vaccine in Healthy Adults

Aichinger

Grohmann-Izay

Velden

et al. 2014

Clin. Vaccine Immunol.

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“…The same Vero cell technology used to manufacture the whole-virus H7N9 vaccine has previously been used to manufacture licensed H1N1pdm09 [16–18,50] and H5N1 vaccines [34,35, 51–54,]. For these vaccines, immunogenicity in non-clinical studies was highly predictive of clinical immunogenicity, as demonstrated in clinical studies for H5N1 [51–54] and H1N1pdm09 [16,18] vaccines, as well as in large-scale use in the field for the whole-virus H1N1pdm09 vaccine [19].…”

Section: Discussionmentioning

confidence: 99%

“…T-helper cell responses induced in immunized mice were analyzed by IFN-γ and IL-4 ELISPOT, and HA-specific IgG subtype analysis was done by ELISA. To investigate a hypothesis that H7N9 vaccines would be less immunogenic than other influenza vaccines [15], we compared the immunogenicity of the novel H7N9 vaccine to a licensed H1N1 (H1N1pdm09) vaccine [16–18] which was widely used in the 2009–2010 pandemic [19]. …”

Section: Introductionmentioning

confidence: 99%

Immunogenicity and Protective Efficacy of a Vero Cell Culture-Derived Whole-Virus H7N9 Vaccine in Mice and Guinea Pigs

et al. 2015

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BackgroundA novel avian H7N9 virus with a high case fatality rate in humans emerged in China in 2013. We evaluated the immunogenicity and protective efficacy of a candidate Vero cell culture-derived whole-virus H7N9 vaccine in small animal models.MethodsAntibody responses induced in immunized DBA/2J mice and guinea pigs were evaluated by hemagglutination inhibition (HI), microneutralization (MN), and neuraminidase inhibition (NAi) assays. T-helper cell responses and IgG subclass responses in mice were analyzed by ELISPOT and ELISA, respectively. Vaccine efficacy against lethal challenge with wild-type H7N9 virus was evaluated in immunized mice. H7N9-specific antibody responses induced in mice and guinea pigs were compared to those induced by a licensed whole-virus pandemic H1N1 (H1N1pdm09) vaccine.ResultsThe whole-virus H7N9 vaccine induced dose-dependent H7N9-specific HI, MN and NAi antibodies in mice and guinea pigs. Evaluation of T-helper cell responses and IgG subclasses indicated the induction of a balanced Th1/Th2 response. Immunized mice were protected against lethal H7N9 challenge in a dose-dependent manner. H7N9 and H1N1pdm09 vaccines were similarly immunogenic.ConclusionsThe induction of H7N9-specific antibody and T cell responses and protection against lethal challenge suggest that the Vero cell culture-derived whole-virus vaccine would provide an effective intervention against the H7N9 virus.

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“…76 Overall efficacy of Vero cell-derived seasonal influenza vaccines has been reported to be 73-82% against antigenically matched and 68-83% against all strains of influenza viruses. 77,78 With the 2009 pandemic A/H1N1 (H1N1pdm09) strain, higher and comparatively longer lasting protective efficacy was reached, with a single dose in adults and older adolescents, and with 2 doses in young adolescents and children, and these responses were boosted strongly by the A/H1N1 component of the seasonal trivalent vaccine. 76,79 Safety profiles of Vero cell-derived influenza vaccines have shown that they are generally as well tolerated as the ECE-derived vaccines.…”

Section: Introductionmentioning

confidence: 99%

Cell culture-based influenza vaccines: A necessary and indispensable investment for the future

Hegde

2015

Human Vaccines & Immunotherapeutics

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Pre-vaccination immunity and immune responses to a cell culture-derived whole-virus H1N1 vaccine are similar to a seasonal influenza vaccine

Cited by 17 publications

References 39 publications

Phase I/II Randomized Double-Blind Study of the Safety and Immunogenicity of a Nonadjuvanted Vero Cell Culture-Derived Whole-Virus H9N2 Influenza Vaccine in Healthy Adults

Phase I/II Randomized Double-Blind Study of the Safety and Immunogenicity of a Nonadjuvanted Vero Cell Culture-Derived Whole-Virus H9N2 Influenza Vaccine in Healthy Adults

Immunogenicity and Protective Efficacy of a Vero Cell Culture-Derived Whole-Virus H7N9 Vaccine in Mice and Guinea Pigs

Cell culture-based influenza vaccines: A necessary and indispensable investment for the future

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