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Development of a stable liquid formulation of live attenuated influenza vaccine.

White JA, Estrada M, Flood EA, Mahmood K, Dhere R, Chen D - Vaccine (2016)

Bottom Line: While live attenuated influenza vaccines are among the most efficacious and can be manufactured at low cost, they may require lyophilization to be stable enough for developing-country use, which adds a significant cost burden.In this study, potential stabilizing excipients were screened and optimized using the least stable influenza vaccine strain presently known, H1N1 (A/California/07/2009), as a model.Through this process, we identified a liquid formulation consisting of sucrose phosphate glutamate buffer with 1% arginine and 0.5% recombinant human serum albumin that provided storage stability of one year at 2-8°C for the influenza A and B strains tested.

View Article: PubMed Central - PubMed

Affiliation: PATH, Seattle, Washington, United States. Electronic address: jawhite@path.org.

No MeSH data available.


Related in: MedlinePlus

Screening of excipients. Formulations were prepared with LAIV H1N1 (A/California/07/2009) in SPG buffer and additional excipients were prepared at a titer of 2 × 106 log10 TCID50/mL. The formulations were stored at 2–8 °C (A) and 25 °C (B), and their titer was measured by TCID50. Formulations were tested for up to 6 weeks or until a titer loss greater than 1 log was observed. N = 1 for each formulation tested by TCID50 in triplicate. Error bars represent the standard deviation of three TCID50 replicates. Abbreviations: BSA; bovine serum albumin.
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fig0005: Screening of excipients. Formulations were prepared with LAIV H1N1 (A/California/07/2009) in SPG buffer and additional excipients were prepared at a titer of 2 × 106 log10 TCID50/mL. The formulations were stored at 2–8 °C (A) and 25 °C (B), and their titer was measured by TCID50. Formulations were tested for up to 6 weeks or until a titer loss greater than 1 log was observed. N = 1 for each formulation tested by TCID50 in triplicate. Error bars represent the standard deviation of three TCID50 replicates. Abbreviations: BSA; bovine serum albumin.

Mentions: In the first formulation stage, excipients were screened for their ability to improve the stability of LAIV compared to the vaccine in SPG buffer alone, as assessed by TCID50 (Fig. 1). All formulations were stable at 2–8 °C for 6 weeks (Fig. 1A). The addition of 1% arginine (Formulation 9) improved the stability of LAIV compared to SPG buffer alone (Formulation 1) at 25 °C. Sorbitol was the worst-performing excipient at 25 °C for both concentrations tested (Fig. 1B). Arginine and BSA were selected as the best-performing excipients for further evaluation.


Development of a stable liquid formulation of live attenuated influenza vaccine.

White JA, Estrada M, Flood EA, Mahmood K, Dhere R, Chen D - Vaccine (2016)

Screening of excipients. Formulations were prepared with LAIV H1N1 (A/California/07/2009) in SPG buffer and additional excipients were prepared at a titer of 2 × 106 log10 TCID50/mL. The formulations were stored at 2–8 °C (A) and 25 °C (B), and their titer was measured by TCID50. Formulations were tested for up to 6 weeks or until a titer loss greater than 1 log was observed. N = 1 for each formulation tested by TCID50 in triplicate. Error bars represent the standard deviation of three TCID50 replicates. Abbreviations: BSA; bovine serum albumin.
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4940209&req=5

fig0005: Screening of excipients. Formulations were prepared with LAIV H1N1 (A/California/07/2009) in SPG buffer and additional excipients were prepared at a titer of 2 × 106 log10 TCID50/mL. The formulations were stored at 2–8 °C (A) and 25 °C (B), and their titer was measured by TCID50. Formulations were tested for up to 6 weeks or until a titer loss greater than 1 log was observed. N = 1 for each formulation tested by TCID50 in triplicate. Error bars represent the standard deviation of three TCID50 replicates. Abbreviations: BSA; bovine serum albumin.
Mentions: In the first formulation stage, excipients were screened for their ability to improve the stability of LAIV compared to the vaccine in SPG buffer alone, as assessed by TCID50 (Fig. 1). All formulations were stable at 2–8 °C for 6 weeks (Fig. 1A). The addition of 1% arginine (Formulation 9) improved the stability of LAIV compared to SPG buffer alone (Formulation 1) at 25 °C. Sorbitol was the worst-performing excipient at 25 °C for both concentrations tested (Fig. 1B). Arginine and BSA were selected as the best-performing excipients for further evaluation.

Bottom Line: While live attenuated influenza vaccines are among the most efficacious and can be manufactured at low cost, they may require lyophilization to be stable enough for developing-country use, which adds a significant cost burden.In this study, potential stabilizing excipients were screened and optimized using the least stable influenza vaccine strain presently known, H1N1 (A/California/07/2009), as a model.Through this process, we identified a liquid formulation consisting of sucrose phosphate glutamate buffer with 1% arginine and 0.5% recombinant human serum albumin that provided storage stability of one year at 2-8°C for the influenza A and B strains tested.

View Article: PubMed Central - PubMed

Affiliation: PATH, Seattle, Washington, United States. Electronic address: jawhite@path.org.

No MeSH data available.


Related in: MedlinePlus