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Vaccine Development Strategies and the Current Status of COVID-19 Vaccines
Published in Debmalya Barh, Kenneth Lundstrom, COVID-19, 2022
Mohsen Akbarian, Kenneth Lundstrom, Elrashdy M. Redwan, Vladimir N. Uversky
In addition to alum, emulsion adjuvants have also been successful in formulating vaccines. For example, AS03 and AS03 emulsion adjuvants are used to increase the immunogenicity of antigens in human vaccines. Compared to alum, AS03 and AS03 emulsion may result in more appropriate responses, probably by recruiting immune cells, improving antigen uptake, and promoting activation of antigen-presenting cells (APCs) [13, 14]. In the case of CoV vaccines, emulsion adjuvants have been used at the pre-clinical level. For example, MF59 has been used in inactivated SARS and MERS vaccines and/or RBD vaccines for MERS-CoV. Emulsions such as MF59-like and alum stabilized Pickering emulsion (PAPE) have also been used to enhance the immune response of protein subunit vaccines against SARS-CoV-2 [8].
Vaccine Adjuvants in Immunotoxicology
Published in Mesut Karahan, Synthetic Peptide Vaccine Models, 2021
Oil-based emulsion adjuvants contain a mixture of oil and aqueous phase which is stabilized with a surfactant. W/O(water/octanol) emulsions provide a strong and long-lasting immune effect. Mineral oil-based emulsions are known to be very efficient; however, they may sometimes cause local reactions with reactive antigens (Aucouturier, Dupuis, and Ganne 2001). Non-mineral oils are well-tolerated, but their immunogenicity is poor. W/O emulsions form a depot at the injection site, thereby causing the antigen to be released slowly. Thus, it may be used to reduce the dose, or the number of doses required for an effective antigen. MF59 is an O/W emulsion adjuvant. Squalene, which is included in its structure, is a triterpenoid hydrocarbon produced abundantly as a precursor of cholesterol and steroid hormones in humans. It is included in the structure of most of the adjuvants due to the fact that it is naturally available in the human body and it is biodegradable. In experimental studies on the less toxic MF59, it was suggested that it was a safe and effective vaccine adjuvant that was well tolerated in humans (Yurdakök and İnce 2008). MF59 has been used for an influenza vaccine for the elderly and young children (Morelli et al. 2012).
Preclinical developments in the delivery of protein antigens for vaccination
Published in Expert Opinion on Drug Delivery, 2023
Dylan A. Hendy, Alex Haven, Eric M. Bachelder, Kristy M. Ainslie
Fluzone (Sanofi Pasteur) and Fluad (Seqirus) represent to inactivated egg produced influenza vaccines that are unadjuvanted and adjuvanted, respectively. Fluzone is the influenza vaccine that is given to the majority of those under 65 in the United States; however, for those over 65 Fluad is recommended. FluAd contains the vaccine adjuvant MF59 which is an oil in water (o/w) emulsion consisting of the oil squalene and two amphiphilic surfactants (Tween 80 and Span 85). MF59 has been shown to improve the immunogenicity of the vaccine and produce a better immune response in the elderly and immunocompromised [20]. When MF59 was first discovered as a vaccine adjuvant, its mechanism of action was unknown. At first, it was thought that it acted as an antigen depot or as a delivery vehicle for antigens. However, further studies revealed that MF59 possesses adjuvanticity independent from antigen delivery [21]. Currently, it is thought that MF59 generates a local immunostimulatory environment at the injection site through the production of chemokines that promotes antigen processing and activation of immune cells [22]. Clinical studies have revealed that FluAd is superior to the unadjuvanted Fluzone in patients that are highly susceptible to influenza such as the elderly [20]. For example, Puig-Barbera et al. showed decreased hospitalization of older adults for pneumonia after vaccination with FluAd [23].
Combined adjuvant-delivery system for new generation vaccine antigens: alliance has its own advantage
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Monika Kaurav, Jitender Madan, M. S. Sudheesh, Ravi Shankar Pandey
Table 3 shows recently approved o/w adjuvant-based biodegradable vaccines such as Prepandrix® (AS03 adjuvanted pre-pandemic influenza), Aflunov® (MF59 adjuvanted pre-pandemic influenza), Fluad® (MF59 adjuvanted seasonal influenza) and Pandremix® (AS03 adjuvanted pandemic influenza). Few MF59 adjuvanted influenza vaccines of Novartis, i.e. Focetria® and Celtura® were discontinued in the year 2015. Fluad, an adjuvanted flu vaccine for elderly peoples was first introduced in the market by Novartis. However, in 2015 Novartis’s all influenza vaccines were acquired by Seqirus vaccine Ltd. (Liverpool, UK) (A CSL company). Furthermore, MF59 in Fluad has been tested in variety of antigens and conducted clinical trials such as HBV, HIV, HSV HCV, CMV and influenza. The emulsion based adjuvant AS03 and AF03 developed by GSK and Sanofi respectively was approved for pandemic influenza. Recently, reoccurrence of narcolepsy attacks was seen with the use of A/H1N1 2009 AS03 adjuvanted vaccine, but not observed with the use of an A/H1N1 2009 MF59 adjuvanted vaccine. Pre-clinical studies showed that AS03 possess α-tocopherol that prompts stimulation of the immune system both in the muscle and lymph nodes. In contrast, MF59 contains squalene emulsions, which induced specific immune activation in the vaccinated muscle only [29].
Synthetic Toll-like receptor agonists for the development of powerful malaria vaccines: a patent review
Published in Expert Opinion on Therapeutic Patents, 2018
Arshpreet Kaur, Deepika Kannan, Surinder K. Mehta, Shailja Singh, Deepak B. Salunke
The overall goal of vaccination is the induction of a strong immune response against the coadministered antigen which should provide a long-term protection against the infection [10]. The early vaccines which generally used killed whole organisms are known to produce several adverse reactions which are associated with the signs and symptoms like fever and sore arm at the injection site. In order to reduce this reactogenicity, new vaccines consist of highly purified antigens with more defined composition. There are distinct advantages in these ‘modern vaccines’ such as safety, quality control, and ease of production. However, such subunit antigens with largely soluble proteins have poor immunogenicity and, therefore, need help. ‘Adjuvants’ are compounds that help these poorly immunogenic antigens to induce a strong and long-lasting immune response [11]. Several natural and synthetic compounds have been identified so far to have adjuvantic activity. The mineral salt ‘Alum’ (aluminum hydroxide) was introduced in the 1920s and used in licensed vaccines all over the world. Alum salts form an antigen depot at the inoculation site from where the antigen is released slowly. After seven decades, Novartis introduced O/W emulsion (MF59) in Europe. MF59 is a potent stimulator of immune response; however, excessive reactogenicity, inflammatory reactions, granuloma, and ulcer at the injection site are the few limitations of MF59. Recently, GSK introduced ‘immune potentiators’ such as Monophosphoryl Lipid A (MPLA) and α-tocopherol in Europe as adjuvants in combination with alum or O/W emulsion.