Vaccine adjuvant activity of emulsified oils from species of the Pinaceae family

Fox, Christopher B.; Hoeven, Neal Van; Granger, Brian; Lin, Susan; Guderian, Jeffrey A.; Hartwig, Airn E.; Marlenee, Nicole L.; Bowen, Richard A.; Soultanov, Vagif; Carter, Darrick

doi:10.1016/j.phymed.2019.152927

Cited by 12 publications

(7 citation statements)

References 20 publications

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“…In an oil-in-water emulsion, the oil is the dispersed phase, in water. The most commonly used oil in human adjuvants is squalene, a naturally occurring molecule found in plants and animals, including humans, in whom it is essential for the production of cholesterol, steroid hormones, and vitamin D. Squalene is a component of all the major emulsion adjuvants (Table 1 ) 11 , 12 and is currently derived from a natural source (shark liver oil), although alternative sources are being explored 2 and advances have been made using both synthetic biology techniques 13 and plant sources 14 , 15 . Squalene-based emulsions are currently mainly manufactured using microfluidizers or high-pressure homogenization.…”

Section: Introductionmentioning

confidence: 99%

“World in motion” – emulsion adjuvants rising to meet the pandemic challenges

et al. 2021

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Emulsion adjuvants such as MF59 and AS03 have been used for more than two decades as key components of licensed vaccines, with over 100 million doses administered to diverse populations in more than 30 countries. Substantial clinical experience of effectiveness and a well-established safety profile, along with the ease of manufacturing have established emulsion adjuvants as one of the leading platforms for the development of pandemic vaccines. Emulsion adjuvants allow for antigen dose sparing, more rapid immune responses, and enhanced quality and quantity of adaptive immune responses. The mechanisms of enhancement of immune responses are well defined and typically characterized by the creation of an “immunocompetent environment” at the site of injection, followed by the induction of strong and long-lasting germinal center responses in the draining lymph nodes. As a result, emulsion adjuvants induce distinct immunological responses, with a mixed Th1/Th2 T cell response, long-lived plasma cells, an expanded repertoire of memory B cells, and high titers of cross-neutralizing polyfunctional antibodies against viral variants. Because of these various properties, emulsion adjuvants were included in pandemic influenza vaccines deployed during the 2009 H1N1 influenza pandemic, are still included in seasonal influenza vaccines, and are currently at the forefront of the development of vaccines against emerging SARS-CoV-2 pandemic variants. Here, we comprehensively review emulsion adjuvants, discuss their mechanism of action, and highlight their profile as a benchmark for the development of additional vaccine adjuvants and as a valuable tool to allow further investigations of the general principles of human immunity.

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Section: Introductionmentioning

confidence: 99%

“World in motion” – emulsion adjuvants rising to meet the pandemic challenges

et al. 2021

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“…Stable emulsions (SEs) were evaluated for innate immunostimulatory activity in whole blood from 6 human subjects (3 male and 3 female) that was purchased anonymized from Bloodworks Northwest (Seattle, USA). The emulsions were incubated with heparinized blood for 18–24 h at 37 °C, and the production of monocyte chemoattractant protein-1 (MCP-1), interleukin 8 (IL-8), and macrophage inflammatory protein-1β (MIP-1β) cytokines was quantified in the supernatants as described previously [ 9 , 39 ]. These cytokines were selected based on their robust modulation with squalene emulsions in our previous studies.…”

Section: Methodsmentioning

confidence: 99%

Screening of Oligomeric (Meth)acrylate Vaccine Adjuvants Synthesized via Catalytic Chain Transfer Polymerization

Hege,

Stimpson,

Sefton

et al. 2023

Polymers

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This report details the first systematic screening of free-radical-produced methacrylate oligomer reaction mixtures as alternative vaccine adjuvant components to replace the current benchmark compound squalene, which is unsustainably sourced from shark livers. Homo-/co-oligomer mixtures of methyl, butyl, lauryl, and stearyl methacrylate were successfully synthesized using catalytic chain transfer control, where the use of microwave heating was shown to promote propagation over chain transfer. Controlling the mixture material properties allowed the correct viscosity to be achieved, enabling the mixtures to be effectively used in vaccine formulations. Emulsions of selected oligomers stimulated comparable cytokine levels to squalene emulsion when incubated with human whole blood and elicited an antigen-specific cellular immune response when administered with an inactivated influenza vaccine, indicating the potential utility of the compounds as vaccine adjuvant components. Furthermore, the oligomers’ molecular sizes were demonstrated to be large enough to enable greater emulsion stability than squalene, especially at high temperatures, but are predicted to be small enough to allow for rapid clearance from the body.

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“…Squalene oil is prominent in oil-in-water emulsions; however, its immunological mechanism around structure/function of the oil composition are not clear [ 166 ]. Further, as the primary source of squalene is from the liver of sharks, this limits its manufacture on a large scale [ 167 ].…”

Section: Emulsions Adjuvantsmentioning

confidence: 99%

“…Further, as the primary source of squalene is from the liver of sharks, this limits its manufacture on a large scale [ 167 ]. Emulsified oils from Pinaceae (pine trees) provide a potentially effective supplementary option, and have been recently assessed as emulsified oil vaccines in mice, pigs and ferrets against pandemic influenza [ 166 ].…”

Section: Emulsions Adjuvantsmentioning

confidence: 99%

Advances in Infectious Disease Vaccine Adjuvants

et al. 2022

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Vaccines are one of the most significant medical interventions in the fight against infectious diseases. Since their discovery by Edward Jenner in 1796, vaccines have reduced the worldwide transmission to eradication levels of infectious diseases, including smallpox, diphtheria, hepatitis, malaria, and influenza. However, the complexity of developing safe and effective vaccines remains a barrier for combating many more infectious diseases. Immune stimulants (or adjuvants) are an indispensable factor in vaccine development, especially for inactivated and subunit-based vaccines due to their decreased immunogenicity compared to whole pathogen vaccines. Adjuvants are widely diverse in structure; however, their overall function in vaccine constructs is the same: to enhance and/or prolong an immunological response. The potential for adverse effects as a result of adjuvant use, though, must be acknowledged and carefully managed. Understanding the specific mechanisms of adjuvant efficacy and safety is a key prerequisite for adjuvant use in vaccination. Therefore, rigorous pre-clinical and clinical research into adjuvant development is essential. Overall, the incorporation of adjuvants allows for greater opportunities in advancing vaccine development and the importance of immune stimulants drives the emergence of novel and more effective adjuvants. This article highlights recent advances in vaccine adjuvant development and provides detailed data from pre-clinical and clinical studies specific to infectious diseases. Future perspectives into vaccine adjuvant development are also highlighted.

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Vaccine adjuvant activity of emulsified oils from species of the Pinaceae family

Cited by 12 publications

References 20 publications

“World in motion” – emulsion adjuvants rising to meet the pandemic challenges

“World in motion” – emulsion adjuvants rising to meet the pandemic challenges

Screening of Oligomeric (Meth)acrylate Vaccine Adjuvants Synthesized via Catalytic Chain Transfer Polymerization

Advances in Infectious Disease Vaccine Adjuvants

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