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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].
Order Blubervirales: Surface Protein
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
The first clinical trial of RTS,S evaluated two formulations, RTS,S/MPL (monophosphoryl lipid A)/alum and RTS,S/alum, developed at GSK for safety and efficacy in malaria naive adults in 1992 at the WRAIR (Gordon et al. 1995). Next, one formulation, RTS,S/AS02A, consisting of RTS,S in an oil-in-water emulsion with MPL and QS21 demonstrated great antibody response (Garçon et al. 2003). In 1996, volunteers immunized with either RTS,S/AS03 (an oil-in-water emulsion without additional adjuvants) or RTS,S/AS02A in a Phase 2A trial at WRAIR developed the highest antirepeat antibody responses ever induced by a CS-based vaccine, but RTS,S/AS02A induced a higher T-cell response as measured by IFN-γ production (Sun et al. 2003). While the RTS,S/AS03 formulation was marginally protective (two of seven), the RTS,S/AS02A protected an unprecedented six of seven volunteers (Stoute et al. 1997).
Peptide Vaccine
Published in Mesut Karahan, Synthetic Peptide Vaccine Models, 2021
Joel Lim Whye Ern, Tan Shen Leng, Tee Yi Na, Palaniarajan Vijayaraj Kumar
In vaccine formulation, emulsions protect antigens from rapid degradation, increase antigen uptake by antigen-presenting cells, and activate the non-specific immune response locally, thereby improving the immune response (Koh et al. 2006). MF59 is the first oil-in-water emulsion of squalene adjuvant, developed in the 1990s by Novartis, composed of squalene oil and surfactant (Span 85 and Tween 80) (O’Hagan et al. 2013). Squalene is a naturally occurring organic compound which offers the potential of a low level of toxicity. Studies showed that MF-59 adjuvanted influenza vaccines had superior immunogenicity than alum adjuvant for influenza vaccine with a high safety profile (O’Hagan 2007; Black 2015). However, MF59 may induce inflammatory arthritis and reactogenicity (Sanina 2019). Another squalene-based adjuvant is GSK’s AS03 used in Pandemrix, a A/H1N1 pandemic flu vaccine.
Development of nano-carriers for Leishmania vaccine delivery
Published in Expert Opinion on Drug Delivery, 2020
Anis Askarizadeh, Ali Badiee, Ali Khamesipour
Immunostimulatory adjuvants which is also called non-particulate adjuvants directly influence the immune system to induce responses to antigens. Most of the adjuvants in this category are pathogen-associated molecular patterns (PAMPs), the molecules that are highly conserved in a broad range of pathogens [21]. PAMPs are recognized by toll-like receptors (TLRs) or nucleotide-binding oligomerization domain-like receptors (NLRs) which provide a basis for many adjuvants [22]. Monophosphoryl lipid A (MPL), muramyl di- or tripeptides and derivatives (MDP/MTP-PE), cytokines (IL-2, IL-12, GM-CSF), saponins (QuilA, QS-21), Detox®, RC-529, glucan, imiquimod, CpG oligonucleotides, and combinations thereof are examples of immunostimulatory adjuvants [23]. In animal model, IL-12 is the most effective adjuvant and almost any Leishmania antigens which was used with IL-12 induced a Th1 response and some degree of protection but the main drawback of IL-12 is the safety issues alongside with the cost and short half-life in vivo [24,25]. An attractive recent strategy for the rational design of potent adjuvants is the combination of immunostimulatory with particulate adjuvants such as AS01®, AS02®, and AS03® to induce a synergistic or additive effect and thereby enhance the immune response.
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].
Influenza vaccine response: future perspectives
Published in Expert Opinion on Biological Therapy, 2018
Chiara Mameli, Enza D’auria, Paola Erba, Pilar Nannini, Gian Vincenzo Zuccotti
Several studies support the observation of a reduced serological response with repeated vaccinations, suggesting that VE may be negatively influenced by prior vaccination, particularly when the antigenic distance between strains in consecutive vaccinations is small, as reported in a recent Japanese study [21]. In this context, the confounding effects of age on the immune response may also play a role. However, these findings are not confirmed by a recent study that showed how a single administration of the adjuvanted H1N1pdm09 vaccine is able to induce durable persistence of protective antibody titers and cross-reactive IFN-γ+CD4+ and CD8+ T cells, up to 4 years after vaccination. This is probably due to the AS03 adjuvant that is shown to increase vaccine immunogenicity. Per this finding, repeated annual vaccination can maintain strain-specific antibodies and T cells and important cross-reactive IFN-γ+CD4+ as well as CD8+ T cells, hence providing evidence to continue annual influenza vaccination [22].