Avanti & Croda-Denmark: Advancing Vaccine Adjuvant Research

In 2020, researchers at Verndari, Inc. investigated a novel microarray skin patch vaccine incorporating subunit glycoprotein antigens and liposomal adjuvants into a trehalose co-formulation. These components form a vaccine system injecting intradermally via a microarray skin patch rather than the typical intramuscular injection mechanism used by other vaccines.

What are the advantages of a microarray skin patch that administers vaccines intradermally?

There are several advantages of an intradermally (ID) administered vaccine over an intramuscularly (IM) administered vaccine. 1) ID administered vaccines have been shown to need 1/10th the dose compared to an IM administered vaccine. 2) A survey conducted in 2012 found that 20% of adults in the United States will not take a vaccine due to fear of needles. Microarray skin patches with an ID administration method would provide a painless alternative and help alleviate some of these fears. 3) There would be a significant cost reduction when using the microarray skin patch vaccine method compared to the historically used IM injection method. Some of the potential cost reductions would occur due to the microarray skin patch being a self-administered vaccine, reduction of the active pharmaceutical ingredient (API) loading, and the ability of the skin patch to be stored for longer durations at warmer temperatures; therefore, mitigating the need for cold-chain storage and delivery channels.

How do liposomal adjuvants aid in accomplishing the goals of a microarray skin patch vaccine?

Adjuvants are known to enhance immune responses to antigens in vaccines. This study combined the use of Avanti’s 3D(6-acyl) phosphorylated hexaacyl disaccharide (PHAD) analog and Croda’s QS-21 adjuvant. Avanti’s 3D(6-acyl) PHAD is a synthetic monophosphorylated lipid A (MPLA) and is most closely related to the reported structure of GSK’s Adjuvant Systems AS01, AS02, and AS04. This adjuvant is fully synthetic and mimics the Toll-like receptor 4 (TLR4) agonist activity of bacterial MPLA. QS-21 is derived from the South American tree, Quillaja Saponaria Molina. It is a potent adjuvant that exhibits low toxicity and high immunostimulatory efficacy.

The combination of these adjuvants in the microarray skin patch vaccine produced a 15-fold reduced dose with comparable, and in some cases more effective, results to the IM injected material. The study was unclear regarding the necessity of 3D(6-acyl)PHAD because a formulation with and without this adjuvant was tested and they were both very effective. The assays used in this study would not detect cell-mediated immunity which may be the adjuvant mechanism used by the TLR-4 agonist, 3D(6-acyl)PHAD. This would explain why there was no difference in efficacy between the PHAD formulated and non-PHAD formulated vaccines in this study, but future studies investigating cell-mediated immunity would be necessary to confirm or deny the need for PHAD adjuvants in this system.

The Bottom Line Robust IgG immune responses were triggered as early as two weeks post-vaccination with QS-21/3D(6-acyl)PHAD adjuvanted virosomes when administered ID. This is just one example of what Avanti and Croda’s adjuvants can accomplish in vaccine research. We are very proud that our products are being used to improve and save people’s lives.

As always, we can’t wait to see what you will do with our high-quality adjuvant systems.