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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

Formulation validation. Lead formulations were evaluated with an alternate LAIV strain, B/Brisbane/60/2008. Formulations of LAIV H1N1 or type B were prepared in SPG buffer or SPG buffer with 1% arginine at a titer of 2 × 106 log10 TCID50/mL. The formulations were stored at 2–8 °C (A), 25 °C (B), and 33 °C (C), and their titer was measured by TCID50. Formulations were tested for up to 52 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.
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fig0015: Formulation validation. Lead formulations were evaluated with an alternate LAIV strain, B/Brisbane/60/2008. Formulations of LAIV H1N1 or type B were prepared in SPG buffer or SPG buffer with 1% arginine at a titer of 2 × 106 log10 TCID50/mL. The formulations were stored at 2–8 °C (A), 25 °C (B), and 33 °C (C), and their titer was measured by TCID50. Formulations were tested for up to 52 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.

Mentions: During the validation stage, LAIV type B (B/Brisbane/60/2008) was formulated with the lead formulation containing 1% arginine (Formulation-09), and the use of SPG buffer alone (Formulation-01) was evaluated for comparison. LAIV formulations with 1% arginine with H1N1 were included to act as a bridge to previous formulation experiments (influenza titer of 2 × 106 log10 TCID50/mL). Consistent with previous experiments, the use of 1% arginine led to statistically significant improvement in stability compared to use of SPG buffer alone at 2–8 °C (p-value <0.0001), 25 °C (p-value <0.0001), and 33 °C (p-value of 0.0002 and 0.003, respectively) for both H1N1 and type B (Fig. 3A–C).


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)

Formulation validation. Lead formulations were evaluated with an alternate LAIV strain, B/Brisbane/60/2008. Formulations of LAIV H1N1 or type B were prepared in SPG buffer or SPG buffer with 1% arginine at a titer of 2 × 106 log10 TCID50/mL. The formulations were stored at 2–8 °C (A), 25 °C (B), and 33 °C (C), and their titer was measured by TCID50. Formulations were tested for up to 52 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.
© Copyright Policy - CC BY
Related In: Results  -  Collection

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

fig0015: Formulation validation. Lead formulations were evaluated with an alternate LAIV strain, B/Brisbane/60/2008. Formulations of LAIV H1N1 or type B were prepared in SPG buffer or SPG buffer with 1% arginine at a titer of 2 × 106 log10 TCID50/mL. The formulations were stored at 2–8 °C (A), 25 °C (B), and 33 °C (C), and their titer was measured by TCID50. Formulations were tested for up to 52 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.
Mentions: During the validation stage, LAIV type B (B/Brisbane/60/2008) was formulated with the lead formulation containing 1% arginine (Formulation-09), and the use of SPG buffer alone (Formulation-01) was evaluated for comparison. LAIV formulations with 1% arginine with H1N1 were included to act as a bridge to previous formulation experiments (influenza titer of 2 × 106 log10 TCID50/mL). Consistent with previous experiments, the use of 1% arginine led to statistically significant improvement in stability compared to use of SPG buffer alone at 2–8 °C (p-value <0.0001), 25 °C (p-value <0.0001), and 33 °C (p-value of 0.0002 and 0.003, respectively) for both H1N1 and type B (Fig. 3A–C).

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