Comparative tissue proteomics reveals unique action mechanisms of vaccine adjuvants

Li, Yibo; Li, Zhuofan; Chen, Xinyuan

doi:10.1016/j.isci.2022.105800

Cited by 4 publications

(4 citation statements)

References 52 publications

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“…Influenza viral challenge was performed as in our previous reports [25,28]. Briefly, mice were anesthetized and inoculated intranasally with 10× LD 50 of mouse-adapted pdm09 viruses.…”

Section: Lethal Viral Challengementioning

confidence: 99%

Differential Regulation of DC Function, Adaptive Immunity, and MyD88 Dependence by Two Squalene Emulsion-Based Vaccine Adjuvants

Nakkala,

Li,

Akter

et al. 2024

Vaccines

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MF59 and AS03 are squalene emulsion-based vaccine adjuvants with similar compositions and droplet sizes. Despite their broad use in licensed influenza vaccines, few studies compared their adjuvant effects and action mechanisms side by side. Considering the majority of adjuvants act on dendritic cells (DCs) to achieve their adjuvant effects, this study compared MF59 and AS03-like adjuvants (AddaVax and AddaS03, respectively) to enhance antigen uptake, DC maturation, ovalbumin (OVA) and seasonal influenza vaccine-induced immune responses. Considering MF59 was reported to activate MyD88 to mediate its adjuvant effects, this study also investigated whether the above-explored adjuvant effects of AddaVax and AddaS03 depended on MyD88. We found AddaVax more potently enhanced antigen uptake at the local injection site, while AddaS03 more potently enhanced antigen uptake in the draining lymph nodes. AddaS03 but not AddaVax stimulated DC maturation. Adjuvant-enhanced antigen uptake was MyD88 independent, while AddaS03-induced DC maturation was MyD88 dependent. AddaVax and AddaS03 similarly enhanced OVA-induced IgG and subtype IgG1 antibody responses as well as influenza vaccine-induced hemagglutination inhibition antibody titers, whileAddaS03 more potently enhanced OVA-specific IgG2c antibody responses. Both adjuvants depended on MyD88 to enhance vaccine-induced antibody responses, while AddaVax depended more on MyD88 to achieve its adjuvant effects. Our study reveals similarities and differences of the two squalene emulsion-based vaccine adjuvants, contributing to our improved understanding of their action mechanisms.

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“…Influenza viral challenge was performed as in our previous reports [25,28]. Briefly, mice were anesthetized and inoculated intranasally with 10× LD 50 of mouse-adapted pdm09 viruses.…”

Section: Lethal Viral Challengementioning

confidence: 99%

Differential Regulation of DC Function, Adaptive Immunity, and MyD88 Dependence by Two Squalene Emulsion-Based Vaccine Adjuvants

Nakkala,

Li,

Akter

et al. 2024

Vaccines

Self Cite

View full text Add to dashboard Cite

show abstract

“… Transfer supernatants to LC-MS/MS vials and store supernatants at −20°C or inject 25 μL for LC-MS/MS analysis as previously described. 1 Pause point: The peptides can be stored at −20°C for several weeks. …”

Section: Step-by-step Methods Detailsmentioning

confidence: 99%

“…This protocol describes in vivo animal treatment with our recently developed physical radiofrequency adjuvant (RFA) 1 , 2 , 3 , 4 , 5 and traditional chemical adjuvants, 6 , 7 , 8 skin collection, and downstream processing to prepare for proteomics LC-MS/MS analysis. The lateral back skin of mice is exposed to the physical RFA treatment or intradermally injected with chemical adjuvants, such as MF59-like AddaVax, monophosphoryl lipid A (MPL), Alum, and MPL/Alum mixture.…”

Section: Before You Beginmentioning

confidence: 99%

“… 9 , 10 The reason to choose intradermal delivery in this protocol is because RFA acts on skin to boost intradermal vaccination. 1 , 2 , 3 , 4 , 5 The delivery of chemical adjuvants into the skin allows the direct comparison of physical and chemical adjuvants-induced tissue proteome changes. However, the procedures described in this protocol can be readily adapted to extract proteins from other tissues (e.g., muscle, draining lymph nodes) or cultured cells (e.g., dendritic cells, peripheral blood mononuclear cells).…”

Section: Before You Beginmentioning

confidence: 99%

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