Adjuvant Discovery via a High Throughput Screen using Human Primary Mononuclear Cells.

Area of Science:

• Biomedical science
• Immunology
• Vaccinology

Background:

• Vaccine efficacy is often limited by poor immunogenicity and inconsistent reactogenicity.
• Adjuvants boost vaccine responses by activating the innate immune system, but current discovery methods are inefficient.
• There is a need for improved strategies to identify novel adjuvant candidates.

Approach:

• Developed a high-throughput, high-content screening protocol using human primary leukocytes (peripheral blood mononuclear cells).
• Screened approximately 2,500 small molecules using a quantitative cytokine and flow cytometry immunoassay.
• Identified hit compounds based on cytokine secretion (TNF, IFNg, IL-10) and PBMC maturation markers.

Key Points:

• Downselected from 197 initial hits to five promising scaffolds, with vinblastine sulfate identified as the top candidate.
• Vinblastine sulfate demonstrated robust in vitro efficacy and potency.
• In vivo studies showed vinblastine sulfate significantly enhanced murine humoral immune responses to SARS-CoV-2 spike protein, increasing IgG titers four-fold.

Conclusions:

• Outlined a novel methodology for discovering immunomodulators with adjuvant potential using in vitro high-throughput screening.
• Identified vinblastine sulfate as a lead compound with demonstrated in vivo adjuvanticity.
• This approach offers a more efficient pathway for preclinical adjuvant discovery and development.