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OVA-PEG-R848 nanocapsules stimulate neonatal conventional and plasmacytoid dendritic cells
Sebastian Wirsching1, Marina Machtakova2, Frauke Borgans1,3
1Children's Hospital, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
Insights
New adjuvant resiquimod (R848) effectively activates infant immune cells. This TLR7/8 agonist, when encapsulated in nanocapsules, shows potential for enhancing neonatal vaccines against infectious diseases.
Area of Science:
- Immunology
- Vaccinology
- Pediatric Infectious Diseases
Background:
- Childhood mortality remains a significant global health challenge, with millions of deaths annually, many from preventable infectious diseases.
- Current neonatal vaccines often require multiple doses, leaving infants vulnerable during their first six months.
- Developing potent vaccines that overcome the immature neonatal immune system is crucial for improving survival rates.
Purpose of the Study:
- To evaluate the potential of toll-like receptor 7/8 (TLR7/8) agonists as adjuvants in neonatal vaccines.
- To demonstrate the efficacy of resiquimod (R848) in activating neonatal immune cells.
- To explore novel methods for co-delivering antigens and adjuvants to infants.
Main Methods:
- Primary peripheral blood dendritic cells from adults and neonates were stimulated with the TLR7/8 agonist resiquimod (R848).
- Resiquimod (R848) was conjugated to polyethylene glycol and encapsulated within ovalbumin nanocapsules for co-delivery with antigen.
- The activation capacity of encapsulated R848 on neonatal dendritic cells was assessed in vitro.
Main Results:
- Resiquimod (R848) demonstrated superior capacity in activating both adult and neonatal primary peripheral blood dendritic cells.
- Ovalbumin nanocapsules successfully co-delivered resiquimod (R848) and antigen in vitro.
- This study is among the first to show that encapsulated R848 can activate neonatal dendritic cells.
Conclusions:
- Encapsulated resiquimod (R848) effectively activates neonatal dendritic cells, suggesting its potential as a neonatal vaccine adjuvant.
- The findings support the development of novel neonatal vaccines incorporating R848 to elicit more robust immune responses.
- This approach could significantly improve the efficacy of vaccines for young infants, reducing childhood mortality.
Abstract:
Childhood mortality represents a major issue with 5. 3 million worldwide deaths of children under 5 years of age in 2019. Approximately half of those deaths can be attributed to easily preventable, infectious diseases. Currently approved neonatal vaccines are typically effective only after multiple doses leaving infants especially vulnerable during the first 6 months of life. Survival rates could be improved significantly by developing new and more potent vaccines that are capable of overcoming inherently tolerogenic neonatal immune systems. TLR agonists have garnered a great deal of attention in recent years due to their extensive capacities to activate innate immunity. Herein, the superior capacity of the TLR7/8 agonist, resiquimod (R848), to activate adult and neonatal primary peripheral blood dendritic cells is demonstrated. Moreover, R848 can be conjugated to polyethylene glycol and encapsulated in ovalbumin nanocapsules to efficiently co-deliver antigen and adjuvant in vitro. This study is among the first to demonstrate the capacity of encapsulated R848 to activate neonatal dendritic cells. These findings support the potential incorporation of R848 as adjuvant in neonatal vaccines, making them more effective in eliciting a robust immune response.
