Urea Improves Stability of Inactivated Polio Vaccine Serotype 3 During Lyophilization and Storage in Dried Formulations

Wei, Qi; Orgel, Scott; Françon, Alain; Randolph, Theodore W.; Carpenter, John F.

doi:10.1016/j.xphs.2018.04.019

Cited by 10 publications

(4 citation statements)

References 24 publications

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“…An increase of emission intensity without any red-shift due to removal of quenching was recently described for TRP residues involved in conformational changes of monomeric transthyretin (Jazaj et al, 2019). However, while the TRP2038-RNA stacking interaction is highly conserved in other enteroviruses (Hadfield et al, 1997), a similar sudden increase of the intrinsic fluorescence intensity is not visible in the respective graphs of four thermostability analyses previously done by other researchers with PV1 or PV3 over a similar temperature range as employed in our nanoDSF (Grimmel et al, 1983;Chen et al, 1997;Qi et al, 2014Qi et al, , 2018. This finding is quite puzzling, as the PV RNA also exited the capsid in these studies, which should consequently result in an analogous destacking and release of the equivalent TRP2038 from fluorescence quenching by the nucleobase.…”

Section: Discussionsupporting

confidence: 66%

“…As the same sequence of events is also observed for in vivo uncoating, our ITF analysis lends further support to the usefulness of controlled heating of enterovirus as appropriate in vitro model for mimicking this process. To our surprise, we found only four previous reports using ITF for the recording of conformational changes in gradually heated enteroviruses, though employing different instruments and all focusing on poliovirus (a member of the C-type enteroviruses) (Grimmel et al, 1983;Chen et al, 1997;Qi et al, 2014;Qi et al, 2018). The outcome of these studies differs from ours by the absence of a recognizable transition associated with B particle formation, the end product of enterovirus uncoating.…”

Section: Discussioncontrasting

confidence: 59%

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nanoDSF: In vitro Label-Free Method to Monitor Picornavirus Uncoating and Test Compounds Affecting Particle Stability

et al. 2020

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Thermal shift assays measure the stability of macromolecules and macromolecular assemblies as a function of temperature. The Particle Stability Thermal Release Assay (PaSTRy) of picornaviruses is based on probes becoming strongly fluorescent upon binding to hydrophobic patches of the protein capsid (e.g., SYPRO Orange) or to the viral RNA genome (e.g., SYTO-82) that become exposed upon heating virus particles. PaSTRy has been exploited for studying the stability of viral mutants, viral uncoating, and the effect of capsid-stabilizing compounds. While the results were usually robust, the thermal shift assay with SYPRO Orange is sensitive to surfactants and EDTA and failed at least to correctly report the effect of excipients on an inactivated poliovirus 3 vaccine. Furthermore, interactions between the probe and capsid-binding antivirals as well as mutual competition for binding sites cannot be excluded. To overcome these caveats, we assessed differential scanning fluorimetry with a nanoDSF device as a label-free alternative. NanoDSF monitors the changes in the intrinsic tryptophan fluorescence (ITF) resulting from alterations of the 3D-structure of proteins as a function of the temperature. Using rhinovirus A2 as a model, we demonstrate that nanoDFS is well suited for recording the temperature-dependence of conformational changes associated with viral uncoating with minute amounts of sample. We compare it with orthogonal methods and correlate the increase in viral RNA exposure with PaSTRy measurements. Importantly, nanoDSF correctly identified the thermal stabilization of RV-A2 by pleconaril, a prototypic pocket-binding antiviral compound. NanoDFS is thus a label-free, high throughput-customizable, attractive alternative for the discovery of capsid-binding compounds impacting on viral stability.

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Section: Discussionsupporting

confidence: 66%

Section: Discussioncontrasting

confidence: 59%

nanoDSF: In vitro Label-Free Method to Monitor Picornavirus Uncoating and Test Compounds Affecting Particle Stability

et al. 2020

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“…They often require complex formulations including numerous excipients [26] such as salts, polysaccharides, amino acids, cryoprotectants, tonicity modifiers and surfactants. Urea was also tested as a classical excipient for virus-based vaccines [31]. Following screening of excipients, calcium chloride, L-lysine, L-proline, P407, sorbitol and urea were identified as useful additives when mixed with trehalose and PVP to offer the best protection for vYF during the freeze-drying process and a thermal stress at 37 °C (F16 formulation, Table 2).…”

Section: Discussionmentioning

confidence: 99%

A spray freeze dried micropellet based formulation proof-of-concept for a yellow fever vaccine candidate

Clénet

Hourquet

Woinet

et al. 2019

European Journal of Pharmaceutics and Biopharmaceutics

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“…The authors noted that MgCl 2 and urea both cause chaotropic effects, which may stabilize the viral particles by preventing agglomeration. 74 Another study in 2018 using inactivated Sabin polio vaccines identified a lyophilized formulation of sIPV containing histidine, mannitol, MgSO 4 , sorbitol, and pluronic F68. 75 The development of a stable, lyophilized IPV could be invaluable for eliminating cold-chain requirements; however, such advantages of improved stability need to be considered in the context that freeze-drying is more costly to manufacture, and there is limited worldwide production capacity.…”

Section: Low-cost and Next-generation Ipv Vaccine Formulationsmentioning

confidence: 99%

Current and next-generation formulation strategies for inactivated polio vaccines to lower costs, increase coverage, and facilitate polio eradication

Kumar

Bird

Holland

et al. 2022

Human Vaccines & Immunotherapeutics

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Implementation of inactivated polio vaccines (IPV) containing Sabin strains (sIPV) will further enable global polio eradication efforts by improving vaccine safety during use and containment during manufacturing. Moreover, sIPV-containing vaccines will lower costs and expand production capacity to facilitate more widespread use in low- and middle-income countries (LMICs). This review focuses on the role of vaccine formulation in these efforts including traditional Salk IPV vaccines and new sIPV-containing dosage forms. The physicochemical properties and stability profiles of poliovirus antigens are described. Formulation approaches to lower costs include developing multidose and combination vaccine formats as well as improving storage stability. Formulation strategies for dose-sparing and enhanced mucosal immunity include employing adjuvants (e.g. aluminum-salt and newer adjuvants) and/or novel delivery systems (e.g. ID administration with microneedle patches). The potential for applying these low-cost formulation development strategies to other vaccines to further improve vaccine access and coverage in LMICs is also discussed.

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Urea Improves Stability of Inactivated Polio Vaccine Serotype 3 During Lyophilization and Storage in Dried Formulations

Cited by 10 publications

References 24 publications

nanoDSF: In vitro Label-Free Method to Monitor Picornavirus Uncoating and Test Compounds Affecting Particle Stability

nanoDSF: In vitro Label-Free Method to Monitor Picornavirus Uncoating and Test Compounds Affecting Particle Stability

A spray freeze dried micropellet based formulation proof-of-concept for a yellow fever vaccine candidate

Current and next-generation formulation strategies for inactivated polio vaccines to lower costs, increase coverage, and facilitate polio eradication

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