Squalene-Based Influenza Vaccine Adjuvants and Their Impact on the Hemagglutinin-Specific B Cell Response

Nguyen-Contant, Phuong; Sangster, Mark Y.; Topham, David J.

doi:10.3390/pathogens10030355

Cited by 30 publications

(24 citation statements)

References 85 publications

(77 reference statements)

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“…Vaccines are a major achievement of modern science, having saved millions of lives from infectious diseases. Vaccines are composed by pathogen components, such as protein fragments, or by live attenuated or inactivated viruses, as in influenza seasonal vaccines [ 16 ]. More recently, pathogen mRNA fragments have been used as antigens, as in the case of some anti-SARS-CoV2 vaccines recently developed [ 34 ].…”

Section: Squalene-based Formulations As Vaccine Adjuvantsmentioning

confidence: 99%

“…Still, the most widely established application of squalene in pharmaceutical formulations is in the field of vaccine adjuvants. The squalene-based oil-in-water ( o / w ) emulsions MF59 (Novartis), AS03 (GlaxoSmithKline, GSK), and AF03 (Sanofi) have been used as adjuvants in vaccines against influenza virus [ 16 ]. These formulations function as antigen delivery systems and potentiators of innate and adaptive immune responses (Table 1; [ 17 , 18 ]).…”

Section: Introductionmentioning

confidence: 99%

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From Sharks to Yeasts: Squalene in the Development of Vaccine Adjuvants

2022

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Squalene is a natural linear triterpene that can be found in high amounts in certain fish liver oils, especially from deep-sea sharks, and to a lesser extent in a wide variety of vegeTable oils. It is currently used for numerous vaccine and drug delivery emulsions due to its stability-enhancing properties and biocompatibility. Squalene-based vaccine adjuvants, such as MF59 (Novartis), AS03 (GlaxoSmithKline Biologicals), or AF03 (Sanofi) are included in seasonal vaccines against influenza viruses and are presently being considered for inclusion in several vaccines against SARS-CoV-2 and future pandemic threats. However, harvesting sharks for this purpose raises serious ecological concerns that the exceptional demand of the pandemic has exacerbated. In this line, the use of plants to obtain phytosqualene has been seen as a more sustainable alternative, yet the lower yields and the need for huge investments in infrastructures and equipment makes this solution economically ineffective. More recently, the enormous advances in the field of synthetic biology provided innovative approaches to make squalene production more sustainable, flexible, and cheaper by using genetically modified microbes to produce pharmaceutical-grade squalene. Here, we review the biological mechanisms by which squalene-based vaccine adjuvants boost the immune response, and further compare the existing sources of squalene and their environmental impact. We propose that genetically engineered microbes are a sustainable alternative to produce squalene at industrial scale, which are likely to become the sole source of pharmaceutical-grade squalene in the foreseeable future.

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Section: Squalene-based Formulations As Vaccine Adjuvantsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

From Sharks to Yeasts: Squalene in the Development of Vaccine Adjuvants

2022

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“…A famous w/o squalene-based emulsion MF59® has been licensed and commonly used in vaccine development and has been proven to be a safe and potent adjuvant for use in influenza vaccines (O'Hagan 2007). Adjuvants AS03 and AF03, also squalenebased emulsions, are registered for administration with influenza vaccines (Nguyen-Contant et al 2021). Squalenebased adjuvants modulate the innate immunity and the T cell component of adaptive immunity, leading to enhanced antibody response outcomes.…”

Section: Emulsionsmentioning

confidence: 99%

Current view on novel vaccine technologies to combat human infectious diseases

Matić

Šantak

2021

Appl Microbiol Biotechnol

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Inactivated and live attenuated vaccines have improved human life and significantly reduced morbidity and mortality of several human infectious diseases. However, these vaccines have faults, such as reactivity or suboptimal efficacy and expensive and time-consuming development and production. Additionally, despite the enormous efforts to develop vaccines against some infectious diseases, the traditional technologies have not been successful in achieving this. At the same time, the concerns about emerging and re-emerging diseases urge the need to develop technologies that can be rapidly applied to combat the new challenges. Within the last two decades, the research of vaccine technologies has taken several directions to achieve safe, efficient, and economic platforms or technologies for novel vaccines. This review will give a brief overview of the current state of the novel vaccine technologies, new vaccine candidates in clinical trial phases 1-3 (listed by European Medicines Agency (EMA) and Food and Drug Administration (FDA)), and vaccines based on the novel technologies which have already been commercially available (approved by EMA and FDA) with the special reference to pandemic COVID-19 vaccines. Key points• Vaccines of the new generation follow the minimalist strategy.• Some infectious diseases remain a challenge for the vaccine development.• The number of new vaccine candidates in the late phase clinical trials remains low.

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“…However, adjuvant use in humans remains very limited, mainly due to safety concerns [127][128][129][130]. Table 1 lists adjuvants that are currently in use, being tested in clinical trials, or of research interest, and describes their influence on Tfh cells.…”

Section: Vaccination Strategies To Promote Tfh Cell Developmentmentioning

confidence: 99%

T Cell/B Cell Interactions in the Establishment of Protective Immunity

Ritzau-Jost

Hutloff

2021

Vaccines

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Follicular helper T cells (Tfh) are the T cell subset providing help to B cells for the generation of high-affinity antibodies and are therefore of key interest for the development of vaccination strategies against infectious diseases. In this review, we will discuss how the generation of Tfh cells and their interaction with B cells in secondary lymphoid organs can be optimized for therapeutic purposes. We will summarize different T cell subsets including Tfh-like peripheral helper T cells (Tph) capable of providing B cell help. In particular, we will highlight the novel concept of T cell/B cell interaction in non-lymphoid tissues as an important element for the generation of protective antibodies directly at the site of pathogen invasion.

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Squalene-Based Influenza Vaccine Adjuvants and Their Impact on the Hemagglutinin-Specific B Cell Response

Cited by 30 publications

References 85 publications

From Sharks to Yeasts: Squalene in the Development of Vaccine Adjuvants

From Sharks to Yeasts: Squalene in the Development of Vaccine Adjuvants

Current view on novel vaccine technologies to combat human infectious diseases

T Cell/B Cell Interactions in the Establishment of Protective Immunity

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