CGAMP/Saponin Adjuvant Combination Improves Protective Response to Influenza Vaccination by Microneedle Patch in an Aged Mouse Model.

Elena V Vassilieva,Dahnide M Taylor,Mark R Prausnitz,Shelly Wang,Song Li,Richard W Compans,Heorhiy Korniychuk

doi:10.3389/fimmu.2020.583251

Elena V Vassilieva, Dahnide M Taylor + Show 5 more

Open Access

https://doi.org/10.3389/fimmu.2020.583251

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Abstract

Current strategies for improving protective response to influenza vaccines during immunosenescence do not adequately protect individuals over 65 years of age. Here, we used an aged mouse model to investigate the potential of co-delivery of influenza vaccine with the recently identified combination of a saponin adjuvant Quil-A and an activator of the STING pathway, 2’3 cyclic guanosine monophosphate–adenosine monophosphate (cGAMP) via dissolving microneedle patches (MNPs) applied to skin. We demonstrate that synergy between the two adjuvant components is observed after their incorporation with H1N1 vaccine into MNPs as revealed by analysis of the immune responses in adult mice. Aged 21-month-old mice were found to be completely protected against live influenza challenge after vaccination with the MNPs adjuvanted with the Quil-A/cGAMP combination (5 µg each) and demonstrated significantly reduced morbidity compared to the observed responses in these mice vaccinated with unadjuvanted MNPs. Analysis of the lung lysates of the surviving aged mice post challenge revealed the lowest level of residual inflammation in the adjuvanted groups. We conclude that combining influenza vaccine with a STING pathway activator and saponin-based adjuvant in MNPs is a novel option for skin vaccination of the immunosenescent population, which is at high risk for influenza.

Highlights

The Global Influenza Mortality project estimated on average 389,000 influenza-associated respiratory deaths annually, of which 67% were among people 65 years and older [1]
Using an aged mouse model, we demonstrated that a novel combination adjuvant consisting of saponin Quil-A and a stimulator of interferon genes (STING) pathway activator cyclic guanosine monophosphate–adenosine monophosphate (cGAMP) is more effective than the current methods in improving the reduced immune response in immunosenescence [3]
Adjuvant Effect of cGAMP/Quil-A Combination Is Preserved in MNPVaccinated Young Adult 10-Week-Old Mice

Summary

Introduction

The Global Influenza Mortality project estimated on average 389,000 influenza-associated respiratory deaths annually, of which 67% were among people 65 years and older [1]. In the United States, the yearly vaccination rate of the population over 65 years old is estimated to be between 60% and 70%; nearly 90% of influenza-related deaths occur in this age group [2]. These numbers clearly demonstrate an inadequate protective immunity elicited by current influenza vaccines in immunosenescent individuals, and underscore the importance of research aimed at Adjuvanted Influenza Vaccine Patches in Aged improving vaccines designed for aged individuals. In the present study we investigate the potential of delivering this adjuvanted formulation to the skin by means of dissolving microneedle patches (MNPs) [4]. The adjuvanted MNPs are attractive as a way to avoid systemic reactogenicity often associated with the administration of adjuvants

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