Differential Regulation of DC Function, Adaptive Immunity, and MyD88 Dependence by Two Squalene Emulsion-Based Vaccine Adjuvants
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 cell...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-05-01
|
| Series: | Vaccines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-393X/12/5/531 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841542669801619456 |
|---|---|
| author | Jayachandra Reddy Nakkala Yibo Li Labone Akter Xinliang Kang Xinyuan Chen |
| author_facet | Jayachandra Reddy Nakkala Yibo Li Labone Akter Xinliang Kang Xinyuan Chen |
| author_sort | Jayachandra Reddy Nakkala |
| collection | DOAJ |
| description | 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 AddaVax and AddaS03 with similar compositions to MF59 and AS03 adjuvants 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, while AddaS03 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. |
| format | Article |
| id | doaj-art-8bf59135a7c7423ab63c0afa5d514b40 |
| institution | Kabale University |
| issn | 2076-393X |
| language | English |
| publishDate | 2024-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj-art-8bf59135a7c7423ab63c0afa5d514b402025-01-13T16:36:34ZengMDPI AGVaccines2076-393X2024-05-0112553110.3390/vaccines12050531Differential Regulation of DC Function, Adaptive Immunity, and MyD88 Dependence by Two Squalene Emulsion-Based Vaccine AdjuvantsJayachandra Reddy Nakkala0Yibo Li1Labone Akter2Xinliang Kang3Xinyuan Chen4Biomedical & Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, 7 Greenhouse Road, Avedisian Hall, Room 480, Kingston, RI 02881, USABiomedical & Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, 7 Greenhouse Road, Avedisian Hall, Room 480, Kingston, RI 02881, USABiomedical & Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, 7 Greenhouse Road, Avedisian Hall, Room 480, Kingston, RI 02881, USABiomedical & Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, 7 Greenhouse Road, Avedisian Hall, Room 480, Kingston, RI 02881, USABiomedical & Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, 7 Greenhouse Road, Avedisian Hall, Room 480, Kingston, RI 02881, USAMF59 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 AddaVax and AddaS03 with similar compositions to MF59 and AS03 adjuvants 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, while AddaS03 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.https://www.mdpi.com/2076-393X/12/5/531MF59AS03AddaVaxAddaS03squaleneemulsion adjuvant |
| spellingShingle | Jayachandra Reddy Nakkala Yibo Li Labone Akter Xinliang Kang Xinyuan Chen Differential Regulation of DC Function, Adaptive Immunity, and MyD88 Dependence by Two Squalene Emulsion-Based Vaccine Adjuvants Vaccines MF59 AS03 AddaVax AddaS03 squalene emulsion adjuvant |
| title | Differential Regulation of DC Function, Adaptive Immunity, and MyD88 Dependence by Two Squalene Emulsion-Based Vaccine Adjuvants |
| title_full | Differential Regulation of DC Function, Adaptive Immunity, and MyD88 Dependence by Two Squalene Emulsion-Based Vaccine Adjuvants |
| title_fullStr | Differential Regulation of DC Function, Adaptive Immunity, and MyD88 Dependence by Two Squalene Emulsion-Based Vaccine Adjuvants |
| title_full_unstemmed | Differential Regulation of DC Function, Adaptive Immunity, and MyD88 Dependence by Two Squalene Emulsion-Based Vaccine Adjuvants |
| title_short | Differential Regulation of DC Function, Adaptive Immunity, and MyD88 Dependence by Two Squalene Emulsion-Based Vaccine Adjuvants |
| title_sort | differential regulation of dc function adaptive immunity and myd88 dependence by two squalene emulsion based vaccine adjuvants |
| topic | MF59 AS03 AddaVax AddaS03 squalene emulsion adjuvant |
| url | https://www.mdpi.com/2076-393X/12/5/531 |
| work_keys_str_mv | AT jayachandrareddynakkala differentialregulationofdcfunctionadaptiveimmunityandmyd88dependencebytwosqualeneemulsionbasedvaccineadjuvants AT yiboli differentialregulationofdcfunctionadaptiveimmunityandmyd88dependencebytwosqualeneemulsionbasedvaccineadjuvants AT laboneakter differentialregulationofdcfunctionadaptiveimmunityandmyd88dependencebytwosqualeneemulsionbasedvaccineadjuvants AT xinliangkang differentialregulationofdcfunctionadaptiveimmunityandmyd88dependencebytwosqualeneemulsionbasedvaccineadjuvants AT xinyuanchen differentialregulationofdcfunctionadaptiveimmunityandmyd88dependencebytwosqualeneemulsionbasedvaccineadjuvants |