Formulation Design, Optimization and In Vivo Evaluations of an α-Tocopherol-Containing Self-Emulsified Adjuvant System using Inactivated Influenza Vaccine

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J Control Release. 2019 Oct 31. pii: S0168-3659(19)30606-6. doi: 10.1016/j.jconrel.2019.10.042. [Epub ahead of print] Formulation Design, Optimization and In Vivo Evaluations of an α-Tocopherol-Containing Self-Emulsified Adjuvant System using Inactivated Influenza Vaccine.

Lodaya RN¹, Kanitkar AP², Friedrich K², Henson D², Yamagata R², Nuti S², Mallet CP², Bertholet S², Amiji MA³, O'Hagan DT².
Author information

1 Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, MA, 02115, USA. Electronic address: rushit.n.lodaya@gsk.com. 2 GSK, Slaoui Centre for Vaccines Research, Rockville, MD, 20850, USA. 3 Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, MA, 02115, USA.

Abstract

α-Tocopherol has been used as an immune supplement in humans, as an emulsion adjuvant component in several veterinary vaccines as well as an immunomodulatory component of AS03, an emulsion adjuvant that was used in an H1N1 pandemic vaccine (Pandemrix). AS03 is manufactured using microfluidization and high-pressure homogenization. Such high energy and complex manufacturing processes make it difficult and expensive to produce emulsion adjuvants on a large scale, especially in developing countries. In this study we have explored simpler, comparatively inexpensive methods, to formulate emulsion adjuvants containing α-tocopherol, that have the potential to be made in any well-established scale-up facility. This might facilitate producing and stock-piling adjuvant doses and therefore aide in pandemic preparedness. We used design of experiment as a tool to explore incorporating α-tocopherol into self-emulsified systems containing squalene oil and polysorbate 80. We created novel self-emulsified adjuvant systems (SE-AS) and evaluated their potency in vivo in BALB/c mice with inactivated quadrivalent influenza vaccine (QIV) and tested the cellular and humoral immune responses against the four vaccine strains.
Copyright ? 2019. Published by Elsevier B.V.


KEYWORDS:

Inactivated Quadrivalent Influenza Vaccine (QIV); Self-Emulsified Adjuvant Systems (SE-AS); Self-emulsification; Squalene; Vaccine Adjuvants; α-tocopherol

PMID: 31678654 DOI: 10.1016/j.jconrel.2019.10.042