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Evaluation of a recombinant human gelatin as a substitute for a hydrolyzed porcine gelatin in a refrigerator-stable Oka/Merck live varicella vaccine.

Liska V, Bigert SA, Bennett PS, Olsen D, Chang R, Burke CJ - J Immune Based Ther Vaccines (2007)

Bottom Line: The stabilizing effect of recombinant human gelatin on VZV (Oka/Merck) potency change during vaccine lyophilization was similar to the experimental vaccine containing porcine-derived gelatin.No statistically significant difference in potency stability was observed between the vaccine formulations stored at any of the temperatures tested.The recombinant human gelatin demonstrated similar ability to stabilize the live attenuated VZV (Oka/Merck) in an experimental, refrigerator-stable varicella vaccine when compared to the vaccine preparation formulated with hydrolyzed porcine gelatin used in currently marketed varicella vaccine.

View Article: PubMed Central - HTML - PubMed

Affiliation: Vaccine Clinical Research, Merck Research Laboratories, P,O, Box 1000, UG3CD28, North Wales, PA 19454, USA. vladimir_liska@merck.com

ABSTRACT

Background: The labile nature of live, attenuated varicella-zoster virus (Oka/Merck) requires robust stabilization during virus bulk preparation and vaccine manufacturing in order to preserve potency through storage and administration. One stabilizing ingredient used in a varicella-zoster virus (VZV) vaccine is hydrolyzed porcine gelatin which represents the major protein/peptide-based excipient in the vaccine formulation.

Methods: In this comparative study, a recombinant human gelatin fragment (8.5 kD) was assessed as a potential replacement for hydrolyzed porcine gelatin in an experimental live, attenuated VZV (Oka/Merck) vaccine. VZV (Oka/Merck) was harvested in two formulations prepared with either a hydrolyzed porcine gelatin or a recombinant human gelatin. Moreover, the viral stability in the experimental VZV (Oka/Merck) vaccines was evaluated under accelerated and real-time conditions in a comparative study.

Results and discussion: The stabilizing effect of recombinant human gelatin on VZV (Oka/Merck) potency change during vaccine lyophilization was similar to the experimental vaccine containing porcine-derived gelatin. Vaccine viral potency changes were comparable in stabilized VZV (Oka/Merck) formulations containing either hydrolyzed porcine gelatin or recombinant human gelatin. No statistically significant difference in potency stability was observed between the vaccine formulations stored at any of the temperatures tested.

Conclusion: The recombinant human gelatin demonstrated similar ability to stabilize the live attenuated VZV (Oka/Merck) in an experimental, refrigerator-stable varicella vaccine when compared to the vaccine preparation formulated with hydrolyzed porcine gelatin used in currently marketed varicella vaccine.

No MeSH data available.


Related in: MedlinePlus

The long-term stability of VZV (Oka/Merck) formulated in hydrolyzed porcine gelatin (SOL-U-PRO), or recombinant human gelatin (FG-5001) stabilized varicella vaccine matrices. The VZV (Oka/Merck) potency change was determined as a difference between the potency of control samples stored at -70°C, and samples stored at 2–8°C (Figure 1A), and -15°C (Figure 1B) for 24 months, and 15°C (Figure 1C) for 12 months, respectively. The value of 0 for the potency loss (change) at time interval 0 months represents the stability model starting at that point. Vaccine samples were analyzed by the VZV plaque assay in format 1 × 12. The VZV potency change is in log10 PFU/mL.
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Figure 1: The long-term stability of VZV (Oka/Merck) formulated in hydrolyzed porcine gelatin (SOL-U-PRO), or recombinant human gelatin (FG-5001) stabilized varicella vaccine matrices. The VZV (Oka/Merck) potency change was determined as a difference between the potency of control samples stored at -70°C, and samples stored at 2–8°C (Figure 1A), and -15°C (Figure 1B) for 24 months, and 15°C (Figure 1C) for 12 months, respectively. The value of 0 for the potency loss (change) at time interval 0 months represents the stability model starting at that point. Vaccine samples were analyzed by the VZV plaque assay in format 1 × 12. The VZV potency change is in log10 PFU/mL.

Mentions: Following lyophilization, vaccine samples were placed in stability chambers tempered at 2–8°C and -15°C for long-term (24 months) stability study under real-time conditions. In order to assess VZV (Oka/Merck) potency stability under accelerated conditions, a set of both types of vaccine samples were also placed in a stability chamber tempered at 15°C for 12 months. The virus potency losses associated with long-term storage (log10 PFU loss per month, linear regression model) at 2–8°C (Fig. 1A), -15°C (Fig. 1B), and 15°C (Fig. 1C), were similar for the two hydrolyzed porcine gelatin- and recombinant human gelatin-containing varicella vaccines (p = 0.94, 0.87, and 0.97, respectively). The loss rate estimates for each type of gelatin-stabilized vaccine, as well as a pooled estimate combining the data from both vaccines are listed in Table 1. No statistically significant difference in potency stability was observed between the vaccine formulations stored at any of the temperatures tested. During the long-term study (24 months) under real-time conditions (2–8°C), the averaged moisture content values of hydrolyzed porcine gelatin-(2.33% ± 0.12 standard error) and recombinant human gelatin-containing (2.27% ± 0.07 std error) vaccine samples were comparable (p = 0.68). No statistically significant trend in moisture content over time at 2–8°C was found for either formulation (p > 0.05).


Evaluation of a recombinant human gelatin as a substitute for a hydrolyzed porcine gelatin in a refrigerator-stable Oka/Merck live varicella vaccine.

Liska V, Bigert SA, Bennett PS, Olsen D, Chang R, Burke CJ - J Immune Based Ther Vaccines (2007)

The long-term stability of VZV (Oka/Merck) formulated in hydrolyzed porcine gelatin (SOL-U-PRO), or recombinant human gelatin (FG-5001) stabilized varicella vaccine matrices. The VZV (Oka/Merck) potency change was determined as a difference between the potency of control samples stored at -70°C, and samples stored at 2–8°C (Figure 1A), and -15°C (Figure 1B) for 24 months, and 15°C (Figure 1C) for 12 months, respectively. The value of 0 for the potency loss (change) at time interval 0 months represents the stability model starting at that point. Vaccine samples were analyzed by the VZV plaque assay in format 1 × 12. The VZV potency change is in log10 PFU/mL.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1808055&req=5

Figure 1: The long-term stability of VZV (Oka/Merck) formulated in hydrolyzed porcine gelatin (SOL-U-PRO), or recombinant human gelatin (FG-5001) stabilized varicella vaccine matrices. The VZV (Oka/Merck) potency change was determined as a difference between the potency of control samples stored at -70°C, and samples stored at 2–8°C (Figure 1A), and -15°C (Figure 1B) for 24 months, and 15°C (Figure 1C) for 12 months, respectively. The value of 0 for the potency loss (change) at time interval 0 months represents the stability model starting at that point. Vaccine samples were analyzed by the VZV plaque assay in format 1 × 12. The VZV potency change is in log10 PFU/mL.
Mentions: Following lyophilization, vaccine samples were placed in stability chambers tempered at 2–8°C and -15°C for long-term (24 months) stability study under real-time conditions. In order to assess VZV (Oka/Merck) potency stability under accelerated conditions, a set of both types of vaccine samples were also placed in a stability chamber tempered at 15°C for 12 months. The virus potency losses associated with long-term storage (log10 PFU loss per month, linear regression model) at 2–8°C (Fig. 1A), -15°C (Fig. 1B), and 15°C (Fig. 1C), were similar for the two hydrolyzed porcine gelatin- and recombinant human gelatin-containing varicella vaccines (p = 0.94, 0.87, and 0.97, respectively). The loss rate estimates for each type of gelatin-stabilized vaccine, as well as a pooled estimate combining the data from both vaccines are listed in Table 1. No statistically significant difference in potency stability was observed between the vaccine formulations stored at any of the temperatures tested. During the long-term study (24 months) under real-time conditions (2–8°C), the averaged moisture content values of hydrolyzed porcine gelatin-(2.33% ± 0.12 standard error) and recombinant human gelatin-containing (2.27% ± 0.07 std error) vaccine samples were comparable (p = 0.68). No statistically significant trend in moisture content over time at 2–8°C was found for either formulation (p > 0.05).

Bottom Line: The stabilizing effect of recombinant human gelatin on VZV (Oka/Merck) potency change during vaccine lyophilization was similar to the experimental vaccine containing porcine-derived gelatin.No statistically significant difference in potency stability was observed between the vaccine formulations stored at any of the temperatures tested.The recombinant human gelatin demonstrated similar ability to stabilize the live attenuated VZV (Oka/Merck) in an experimental, refrigerator-stable varicella vaccine when compared to the vaccine preparation formulated with hydrolyzed porcine gelatin used in currently marketed varicella vaccine.

View Article: PubMed Central - HTML - PubMed

Affiliation: Vaccine Clinical Research, Merck Research Laboratories, P,O, Box 1000, UG3CD28, North Wales, PA 19454, USA. vladimir_liska@merck.com

ABSTRACT

Background: The labile nature of live, attenuated varicella-zoster virus (Oka/Merck) requires robust stabilization during virus bulk preparation and vaccine manufacturing in order to preserve potency through storage and administration. One stabilizing ingredient used in a varicella-zoster virus (VZV) vaccine is hydrolyzed porcine gelatin which represents the major protein/peptide-based excipient in the vaccine formulation.

Methods: In this comparative study, a recombinant human gelatin fragment (8.5 kD) was assessed as a potential replacement for hydrolyzed porcine gelatin in an experimental live, attenuated VZV (Oka/Merck) vaccine. VZV (Oka/Merck) was harvested in two formulations prepared with either a hydrolyzed porcine gelatin or a recombinant human gelatin. Moreover, the viral stability in the experimental VZV (Oka/Merck) vaccines was evaluated under accelerated and real-time conditions in a comparative study.

Results and discussion: The stabilizing effect of recombinant human gelatin on VZV (Oka/Merck) potency change during vaccine lyophilization was similar to the experimental vaccine containing porcine-derived gelatin. Vaccine viral potency changes were comparable in stabilized VZV (Oka/Merck) formulations containing either hydrolyzed porcine gelatin or recombinant human gelatin. No statistically significant difference in potency stability was observed between the vaccine formulations stored at any of the temperatures tested.

Conclusion: The recombinant human gelatin demonstrated similar ability to stabilize the live attenuated VZV (Oka/Merck) in an experimental, refrigerator-stable varicella vaccine when compared to the vaccine preparation formulated with hydrolyzed porcine gelatin used in currently marketed varicella vaccine.

No MeSH data available.


Related in: MedlinePlus