Development of a stable liquid formulation of live attenuated influenza vaccine

Jessica A White,Marcus Estrada,E Alexander Flood,Kutub Mahmood,Rajeev Dhere,Dexiang Chen

doi:10.1016/j.vaccine.2016.04.074

Jessica A White, Marcus Estrada + Show 4 more

Open Access

https://doi.org/10.1016/j.vaccine.2016.04.074

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Abstract

Vaccination is the most effective means of preventing influenza. However, the cost of producing annual seasonal influenza vaccines puts them out of reach for most developing countries. 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. The development of a liquid live attenuated seasonal influenza vaccine that is stable for around a year—the duration of an annual influenza season—would significantly improve not only the production output but also the use and accessibility of influenza vaccines in low-resource settings.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. The stability-conferring properties of the lead formulations were also tested with a Type B strain of influenza virus (B/Brisbane/60/2008). Stability was also evaluated with higher titers of influenza virus and exposure to agitation and freeze–thaw stresses to further confirm the stability of the lead formulations. 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.

Highlights

Seasonal influenza affects millions of people each year, causing morbidity, mortality, and economic loss [1]
In the first formulation stage, excipients were screened for their ability to improve the stability of LAIV compared to the vaccine in sucrose phosphate glutamate (SPG) buffer alone, as assessed by tissue culture infectious dose50 (TCID50) (Fig. 1)
Formulations containing 1% arginine held at 25 ◦C and 33 ◦C showed improved stability compared to those using SPG buffer alone

Summary

Introduction

Seasonal influenza affects millions of people each year, causing morbidity, mortality, and economic loss [1]. Influenza strains are characterized by surface glycoproteins and are classified into three types: A, B, and C strains. Because only strains A and B cause respiratory disease, vaccines target these subtypes. Influenza viruses are further categorized based on antigenic determinants in their surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) [2,4]. Influenza viruses undergo constant antigenic drift and antigenic shift. Antigenic shift occurs when two influenza strains exchange genome segments in a process called reassortment, resulting in a new virus [3]. Recommended influenza vaccines change each year due to frequent, rapid changes in antigenic determinants in circulating strains [5]. Immune responses generated by vaccination are directed against the HA and NA proteins [4]

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