Vaccine adjuvant uses of poly-IC and derivatives

Abstract

Pathogen-associated molecular patterns (PAMPs) are stand-alone immunomodulators or ‘danger signals,’ that are increasingly recognized as critical components of many modern vaccines. Polyinosinic-polycytidylic acid (poly-IC) is a synthetic dsRNA that can activate multiple elements of the host defense in a pattern that parallels that of a viral infection. When properly combined with an antigen, it can be utilized as a PAMP-adjuvant, resulting in modulation and optimization of the antigen-specific immune response. We briefly review the preclinical and clinical uses of poly-IC and two poly-IC derivatives, poly-IC₁₂U (Ampligen) and poly-ICLC (Hiltonol), as vaccine adjuvants.

Keywords:

• Adaptive immunity
• adjuvant
• ampligen
• hiltonol
• innate immunity
• interferons
• PAMP
• poly-IC
• poly-ICLC
• TLR3
• vaccine

Disclaimer & Acknowledgements

This study was supported with funding from the Department of Defense DTRA project number CB2630. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the US Army.

Financial & competing interests disclosure

KAO Martins is an employee of ORISE and contractor with the Department of Defense. Funding through the Department of Defense, DTRA/JSTO. AM Salazar is CEO of Oncovir, Inc. and is both employed by and owns stock in Oncovir, Inc., which is developing poly-ICLC. S Bavari is a US federal government employee. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Modern vaccines often lack the pathogen-associated molecular pattern danger signal that is critical to natural immunogenicity.

• Polyinosinic-polycytidylic acid (poly-IC) and similar molecules can establish a transient, nonspecific, broad-spectrum, antiviral and antineoplastic effect.

• Poly-IC and its derivatives, when properly presented with an antigen, can generate a ‘live virus vaccine equivalent’ with a comprehensive immune response most suited to antiviral and antineoplastic action. This elicited response includes the following:

– Activation of multiple elements of innate immunity.

– Activation of APCs and antigen processing.

– Generation of a polyfunctional cytotoxic T lymphocyte response.

– Targeting of that response to tumor or pathogens via chemokines.

– Generation of memory T and B cells, antibodies and long-term immunity.

– Induction of various costimulatory factors.

– Increase in Teff/Treg ratios and synergy with blockers of cytotoxic lymphocyte action, such as anti-PD-L1.

Notes