Abstract
Oral immunization using whole inactivated influenza virus vaccine promises an efficient vaccination strategy. While oral vaccination was hampered by harsh gastric environment, a systematic understanding about vaccine destabilization mechanisms was not performed. Here, we investigated the separate and combined effects of temperature, retention time, pH, and osmotic stress on the stability of influenza vaccine by monitoring the time-dependent morphological change using stopped-flow light scattering. When exposed to osmotic stress, clustering of vaccine particles was enhanced in an acidic medium (pH 2.0) at ≥25°C. Fluorescence spectroscopic studies showed that hyper-osmotic stress at pH 2.0 and 37°C caused a considerable increase in conformational change of antigenic proteins compared to that in acidic iso-osmotic medium. A structural integrity of membrane was destroyed upon exposure to hyper-osmotic stress, leading to irreversible morphological change, as observed by undulation in stopped-flow light scattering intensity and transmission electron microscopy. Consistent with these analyses, hemagglutination activity decreased more significantly with an increasing magnitude of hyper-osmotic stress than in the presence of the hypo- and iso-osmotic stresses. This study shows that the magnitude and direction of the osmotic gradient has a substantial impact on the stability of orally administrated influenza vaccine.
Highlights
Severe respiratory disease with substantial morbidity and mortality was associated with influenza viral infection [1]
PC-liposomes function as a reference because their size can be determined from dynamic light scattering (DLS) while the equivalent stopped-flow light scattering (SFLS) spectrum from the same liposomes can be obtained
In this work, we investigated destabilization mechanisms of whole inactivated influenza virus vaccine in gastric digestion environment using SFLS, focusing on the demonstration of how temperature, pH, and osmotic pressure affect the stability of vaccine during digestion process
Summary
Severe respiratory disease with substantial morbidity and mortality was associated with influenza viral infection [1]. The fact that vaccination is the most efficient strategy to prepare for the continuing threat of influenza calls attention to the developments of alternate vaccine, advanced vaccine delivery method, and dose sparing technologies [4]. The inactivated and live attenuated trivalent vaccines produced in embryonated hen’s egg have been used for intramuscular (IM)/intradermal (ID) and intranasal (IN) administration in the U.S [5,6]. There has been extensive research on the development of needle-free vaccine delivery methods and formulations, thereby enabling easier, safer, and cheaper vaccinations in a timelier manner [7]. Among various mucosal vaccination methods, IN administration with the live attenuated influenza vaccine is currently allowed for use in healthy persons aged 5–49 years [5]. An inactivated IN vaccine formulation containing adjuvant was withdrawn from the market due to the safety issues such as causing Bell’s palsy [9,10]
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