Quantification of influenza virus hemagglutinins in complex mixtures using isotope dilution tandem mass spectrometry

Williams, Tracie L.; Luna, Leah G.; Guo, Zhu; Cox, Nancy J.; Pirkle, James L.; Donis, Ruben O.; Barr, John R.

doi:10.1016/j.vaccine.2008.03.014

Cited by 81 publications

(77 citation statements)

References 30 publications

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“…As noted earlier, several newer technologies are under investigation as potential influenza potency assays 12 , 13 , 14 , 15 . At the present time, though, none of the newer techniques has been shown to be as practical as the SRID for standardized testing nor has any been shown to measure a biological function of the HA antigen that can be correlated with clinical benefit.…”

Section: Discussionmentioning

confidence: 98%

“…As a result of these considerations, and the fact that the vaccine potency as determined by SRID correlates with vaccine immunogenicity 7 , 8 , 9 , 10 which correlates with clinical benefit, 11 the SRID assay has been adopted and implemented worldwide by manufacturers and regulatory agencies to determine the potency of inactivated influenza vaccines. Although several alternative methods for HA quantification including techniques based on HPLC, 12 , 13 mass spectrometry, 14 and surface plasmon resonance (SPR) 15 have recently been described, none has yet been demonstrated to be suitable as a viable replacement assay, and the SRID technique remains as the standard method for testing and control of inactivated influenza vaccines.…”

Section: Introductionmentioning

confidence: 99%

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Determination of H5N1 vaccine potency using reference antisera from heterologous strains of influenza

Vodeiko

Weir

2011

Influenza Resp Viruses

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Please cite this paper as: Vodeiko and Weir (2011). Determination of H5N1 vaccine potency using reference antisera from heterologous strains of influenza. Influenza and Other Respiratory Viruses 6(3), 176–187. Background Standardization of inactivated influenza vaccines by hemagglutinin (HA) content is performed by the single radial immunodiffusion (SRID) method. Regulatory agencies prepare, calibrate, and distribute SRID reagent standards necessary for testing of seasonal influenza vaccines, and a similar process is used to produce potency reagents for candidate pandemic influenza vaccines that are manufactured for emergency stockpiles. Objectives Because of the concerns in generating a timely strain‐specific potency antiserum for an emerging pandemic virus, we evaluated the feasibility of using heterologous potency reference antiserum as a replacement for a strain‐specific (homologous) antiserum in the SRID potency assay for stockpiled H5N1 vaccines. Results The results indicate that a heterologous H5N1 antiserum can be used to determine the accurate potency of inactivated H5N1 influenza vaccines. Additionally, when H5N1 vaccine was subjected to an accelerated stability protocol, both homologous and heterologous antisera provided similar measurements of vaccine potency decline. Limitations to the heterologous antiserum approach to potency determination were shown by the inability of antiserum to recent seasonal H1N1 viruses to work in an SRID assay with the 2009 pandemic H1N1 A/California/07/2009 antigen. Conclusions The data demonstrate the feasibility of using heterologous antiserum for potency determination of at least some candidate vaccines in case of a shortage or delay of homologous antiserum. Further, the results suggest the prudence of stockpiling a broad library of potency reagents including many strains of influenza viruses with pandemic potential to provide an added measure of assurance that reagent production would not be a bottleneck to vaccine production during a pandemic.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Determination of H5N1 vaccine potency using reference antisera from heterologous strains of influenza

Vodeiko

Weir

2011

Influenza Resp Viruses

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“…Mass spectrometry (MS) techniques are able to accurately quantify HA in vaccines,33, 34, 35 and the isotope‐dilution MS (IDMS) method is able to quantify the HA subtypes in a multivalent vaccine, and using common tryptic peptides is not dependent upon strain‐specific standards 34, 35. Despite these notable advantages, IDMS is not stability‐indicating and the technique must be coupled with other methods to measure only conformationally correct HA.…”

Section: New Assay Developmentmentioning

confidence: 99%

Standardisation of inactivated influenza vaccines—Learning from history

Wood

Weir

2018

Influenza Resp Viruses

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The single radial immunodiffusion assay has been the accepted method for determining the potency of inactivated influenza vaccines since 1978. The worldwide adoption of this assay for vaccine standardisation was facilitated through collaborative studies that demonstrated a high level of reproducibility and its applicability to the different types of influenza vaccine being produced at that time. Clinical evidence indicated the relevance of SRID as a potency assay. Unique features of the SRID assay are likely responsible for its longevity even as newer technologies for vaccine characterisation have been developed and refined. Nevertheless, there are significant limitations to the SRID assay that indicate the need for improvement, and there has been a substantial amount of work undertaken in recent years to develop and evaluate alternative potency assays, including collaborative studies involving research laboratories, regulatory agencies and vaccine manufacturers. Here, we provide an overview of the history of inactivated influenza vaccine potency testing, the current state of alternative assay development and the some of the major challenges to be overcome before implementation of new assays for potency determination.

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“…To date, antibody-independent assays, such as reversed phase high pressure liquid chromatography (RP-HPLC), 17,18 isotope dilution mass spectrometry 19 and SDS-PAGE, 20 can determine the amount of HA present but denature the HA before measurement. Therefore, they are non-conformational and do not distinguish HA that can elicit protective antibodies (immunologically active HA) from misfolded or denatured HA that is unlikely to elicit potently protective immune responses.…”

Section: Alternative Potency Assaysmentioning

confidence: 99%

Bringing influenza vaccines into the 21st century

Settembre

Dormitzer

Rappuoli

2013

Human Vaccines & Immunotherapeutics

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T he recent H7N9 influenza outbreak in China highlights the need for influenza vaccine production systems that are robust and can quickly generate substantial quantities of vaccines that target new strains for pandemic and seasonal immunization. Although the influenza vaccine system, a public-private partnership, has been effective in providing vaccines, there are areas for improvement. Technological advances such as mammalian cell culture production and synthetic vaccine seeds provide a means to increase the speed and accuracy of targeting new influenza strains with mass-produced vaccines by dispensing with the need for egg isolation, adaptation, and reassortment of vaccine viruses. New influenza potency assays that no longer require the time-consuming step of generating sheep antisera could further speed vaccine release. Adjuvants that increase the breadth of the elicited immune response and allow dose sparing provide an additional means to increase the number of available vaccine doses. Together these technologies can improve the influenza vaccination system in the near term. In the longer term, disruptive technologies, such as RNA-based flu vaccines and 'universal' flu vaccines, offer a promise of a dramatically improved influenza vaccine system.

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Quantification of influenza virus hemagglutinins in complex mixtures using isotope dilution tandem mass spectrometry

Cited by 81 publications

References 30 publications

Determination of H5N1 vaccine potency using reference antisera from heterologous strains of influenza

Determination of H5N1 vaccine potency using reference antisera from heterologous strains of influenza

Standardisation of inactivated influenza vaccines—Learning from history

Bringing influenza vaccines into the 21st century

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