Carbohydrate-based immune adjuvants

Abstract

The role for adjuvants in human vaccines has been a matter of vigorous scientific debate, with the field hindered by the fact that for over 80 years, aluminum salts were the only adjuvants approved for human use. To this day, alum-based adjuvants, alone or combined with additional immune activators, remain the only adjuvants approved for use in the USA. This situation has not been helped by the fact that the mechanism of action of most adjuvants has been poorly understood. A relative lack of resources and funding for adjuvant development has only helped to maintain alum’s relative monopoly. To seriously challenge alum’s supremacy a new adjuvant has many major hurdles to overcome, not least being alum’s simplicity, tolerability, safety record and minimal cost. Carbohydrate structures play critical roles in immune system function and carbohydrates also have the virtue of a strong safety and tolerability record. A number of carbohydrate compounds from plant, bacterial, yeast and synthetic sources have emerged as promising vaccine adjuvant candidates. Carbohydrates are readily biodegradable and therefore unlikely to cause problems of long-term tissue deposits seen with alum adjuvants. Above all, the Holy Grail of human adjuvant development is to identify a compound that combines potent vaccine enhancement with maximum tolerability and safety. This has proved to be a tough challenge for many adjuvant contenders. Nevertheless, carbohydrate-based compounds have many favorable properties that could place them in a unique position to challenge alum’s monopoly over human vaccine usage.

Keywords::

• adjuvants
• carbohydrate
• glucan
• glycomics
• immunity
• inulin
• vaccines

Disclaimer

The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases, National Institutes of Health.

Financial & competing interests disclosure

The authors are both affiliated with Vaxine Pty Ltd, a company holding intellectual property in the area of polysaccharide adjuvant technology. The authors are also supported by Contracts No. U01AI061142 and HHSN272200800039C administered by the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services. 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.