Production and characterization of mammalian virus-like particles from modified vaccinia virus Ankara vectors expressing influenza H5N1 hemagglutinin and neuraminidase

Schmeisser, Falko; Adamo, Joan E.; Blumberg, Benjamin M.; Friedman, Rachel; Müller, Jacqueline; Soto, Jackeline; Weir, Jerry P.

doi:10.1016/j.vaccine.2012.03.033

Cited by 22 publications

(26 citation statements)

References 26 publications

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“…Selection of escape mutant influenza viruses was performed in MDCK cells [23]. Modified vaccinia virus Ankara (MVA) vectors expressing influenza hemagglutinin (HA) have been described previously [24, 25] and were propagated and titered in DF-1 cells. All methods for the generation, propagation, and preparation of recombinant viruses were essentially as described by Earl et al [26].…”

Section: Methodsmentioning

confidence: 99%

“…All methods for the generation, propagation, and preparation of recombinant viruses were essentially as described by Earl et al [26]. Mammalian VLPs containing influenza HA were prepared by MVA vector infection of Vero cells and purified on 10–45% sucrose gradients as previously described [24]. DF-1 and Vero cells were originally obtained from ATCC (CRL-12203 and CCL-81, respectively).…”

Section: Methodsmentioning

confidence: 99%

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Determination of influenza B identity and potency in quadrivalent inactivated influenza vaccines using lineage-specific monoclonal antibodies

et al. 2017

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Co-circulation of two antigenically and genetically distinct lineages of influenza B virus, represented by prototype viruses B/Victoria/2/1987 and B/Yamagata/16/1988, has led to the development of quadrivalent influenza vaccines that contain two influenza B antigens. The inclusion of two influenza B antigens presents challenges for the production and regulation of inactivated quadrivalent vaccines, including the potential for cross-reactivity of the reagents used in identity and potency assays because of the relative close relatedness of the hemagglutinin (HA) from the two virus lineages. Monoclonal antibodies (mAbs) specific for the two lineages of influenza B HA were generated and characterized and used to set-up simple identity tests that distinguish the influenza B antigens in inactivated trivalent and quadrivalent vaccines. The lineage-specific mAbs bound well to the HA of influenza B strains included in influenza vaccines over a period of more than 10 years, suggesting that identity tests using such lineage-specific mAbs would not necessarily have to be updated with every influenza B vaccine strain change. These lineage-specific mAbs were also used in an antibody capture ELISA format to quantify HA in vaccine samples, including monovalent, trivalent, and quadrivalent vaccine samples from various manufacturers. The results demonstrated correlation with HA values determined by the traditional single radial immunodiffusion (SRID) assay. Further, the antibody-capture ELISA was able to distinguish heat-stressed vaccine from unstressed vaccine, and was similar to the SRID in quantifying the resultant loss of potency. These mAb reagents should be useful for further development of antibody-based alternative influenza B identity and potency assays.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Determination of influenza B identity and potency in quadrivalent inactivated influenza vaccines using lineage-specific monoclonal antibodies

et al. 2017

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“…Selection and characterization of A(H7N9) escape viruses were performed in Madin‐Darby canine kidney (MDCK) cells. Mammalian virus‐like particles (VLPs) containing the HA of the A(H7N9) A/Shanghai/2/2013 virus were prepared by modified vaccinia virus Ankara (MVA) vector infection of Vero cells and purified as previously described 16. All virus and VLP work was approved by the FDA's Institutional Biosafety Committee.…”

Section: Methodsmentioning

confidence: 99%

Potency determination of inactivated H7 influenza vaccines using monoclonal antibody‐based ELISA and biolayer interferometry assays

Vasudevan

Woerner

Schmeisser

et al. 2017

Influenza Resp Viruses

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BackgroundThe single radial immunodiffusion (SRID) assay, the accepted method for determining potency of inactivated influenza vaccines, measures an immunogenic form of the influenza hemagglutinin. Nevertheless, alternative methods for measuring vaccine potency have been explored to address some of the weaknesses of the SRID assay, including limited sensitivity and the requirement for large amounts of standardized reagents. Monoclonal antibody (mAb)‐based potency assays also have the ability to detect and measure relevant immunogenic forms of HA.ObjectivesThe objective of this study was to continue evaluation of mAb‐based alternative methods for measuring the potency of inactivated influenza vaccines, focusing on A(H7N9) pandemic influenza vaccines.MethodsSeveral murine mAbs that recognize different epitopes on the H7 hemagglutinin (HA) were identified and characterized. These mAbs were evaluated in both a mAb‐capture ELISA and a mAb‐based biolayer interferometry (BLI) assay.ResultsResults indicated that potency of inactivated A(H7N9) vaccines, including vaccine samples that were stressed by heat treatment, measured by either alternative method correlated well with potency determined by the traditional SRID potency assay.ConclusionsThe availability of multiple H7 mAbs, directed to different HA epitopes, provides needed redundancy in the potency analysis as A(H7N9) viruses continue to evolve antigenically and suggests the importance of having a broad, well‐characterized panel of mAbs available for development of vaccines against influenza strains with pandemic potential. In addition, the results highlight the potential of mAb‐based platform such as ELISA and BLI for development as alternative methods for determining the potency of inactivated influenza vaccines.

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“…Inactivated influenza viruses were analyzed by sodium dodecyl sulfate (SDS)‐polyacrylamide gel electrophoresis and western blot analysis as previously described 18 . Detection was by chemiluminescence (SuperSignal West Dura extended‐duration substrate; Pierce, Rockford, IL, USA) using a LAS‐3000 imager (Fujifilm Medical Systems, Stamford, CT, USA).…”

Section: Methodsmentioning

confidence: 99%

Neutralizing and protective epitopes of the 2009 pandemic influenza H1N1 hemagglutinin

Schmeisser

Friedman

Besho

et al. 2012

Influenza and Other Respiratory Viruses

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Aims and Methods To facilitate antigenic characterization of the influenza A 2009 pandemic H1N1 [A(H1N1)pdm09] hemagglutinin (HA), we generated a panel of murine monoclonal antibodies (mAbs) using as the immunogen mammalian‐derived virus‐like particles containing the HA of the A/California/04/2009 virus. The antibodies were specific for the A/California/04/2009 HA, and individual mAbs suitable for use in several practical applications including ELISA, immunofluorescence, and Western blot analysis were identified. Results and Conclusions As the panel of mAbs included antibodies with hemagglutination inhibition (HI) and virus neutralizing activities, this allowed identification and characterization of potentially important antigenic and neutralizing epitopes of the A/California/04/2009 HA and comparison of those epitopes with the HAs of other influenza viruses including seasonal H1N1 viruses as well as the A/South Carolina/1918 and A/New Jersey/1976 H1N1 viruses. Three mAbs with the highest HI and neutralizing titers were able to provide passive protection against virus challenge. Two other mAbs without HI or neutralizing activities were able to provide partial protection against challenge. HA epitopes recognized by the strongest neutralizing mAbs in the panel were identified by isolation and selection of virus escape mutants in the presence of individual mAbs. Cloned viruses resistant to HI and antibody neutralization were sequenced to identify mutations, and two unique mutations (D127E and G155E) were identified, both near the antigenic site Sa. Using human post‐vaccination sera, however, there were no differences in HI titer between A/California/04/2009 and either escape mutant, suggesting that these single mutations were not sufficient to abrogate a protective antibody response to the vaccine.

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Production and characterization of mammalian virus-like particles from modified vaccinia virus Ankara vectors expressing influenza H5N1 hemagglutinin and neuraminidase

Cited by 22 publications

References 26 publications

Determination of influenza B identity and potency in quadrivalent inactivated influenza vaccines using lineage-specific monoclonal antibodies

Determination of influenza B identity and potency in quadrivalent inactivated influenza vaccines using lineage-specific monoclonal antibodies

Potency determination of inactivated H7 influenza vaccines using monoclonal antibody‐based ELISA and biolayer interferometry assays

Neutralizing and protective epitopes of the 2009 pandemic influenza H1N1 hemagglutinin

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