Adjuvants—Past, Present, and Future Nicholas I. Obiri, Ph.D. and Nathalie Garcon

Question

Adjuvants—Past, Present, and Future

Nicholas I. Obiri, Ph.D. and Nathalie Garcon, Pharm.D., Ph.D.

FAbstract
ollowing the serendipitous discovery that addition of foreign material could enhance immune response to vaccines, alum (aluminum sulfate salts) was identi ed

in 1926 as a potent adjuvant. For many years subsequently, alum remained the only adjuvant in general use for vaccine formulation. As whole pathogens are being replaced by pathogen subunits for vaccine use and signi cant progress
is being made in manufacturing and biotechnology, it is possible to produce large amounts of highly puri ed subunit vaccines. However, the resulting lots are observed to be less immunogenic, and larger vaccine dose amounts are required to achieve protective vaccine e ects. E orts to address these challenges through adjuvant development have been slow. Recent advances in the elds of immunology and molecular biology, such as the identi cation and characterization of host pattern recognition receptors, have led to the discovery of new adjuvants and the potential for even more. Ideally, these newer adjuvants should activate speci c signal pathways that will safely direct and amplify host immune response to vaccines. To meet the increasing worldwide need for vaccination, this newer approach to adjuvant development and others like it will need to be more vigorously pursued. Ideas for facilitating these approaches are discussed.

Introduction

e concept of vaccination was preceded in the 10th century in China and the 16th century in Africa by inoculation with infectious uids from smallpox-infected individuals into naive individuals to protect them against the disease. is inoculation procedure (called variolation) was brought to Europe and the Americas around 1720. Vaccination began to replace variolation in 1798, when Edward Jenner published an in uential paper on protection from smallpox by inocula- tion with cowpox materials. Decades later, vaccination led to development of vaccines against other infectious agents with live-attenuated or killed pathogen-based vaccines, or by inac- tivated toxins [1]. New approaches have followed, such as split pathogens or puri ed antigens extracted from the pathogen

or produced through recombinant technologies. Because pathogens cannot always be grown in the quantities needed
to produce vaccines, the vast majority of today’s vaccines use puri ed antigens manufactured under large-scale manufac- turing conditions that are compliant with good manufacturing practices (GMP). Puri ed antigens may lack many features
of the original pathogens, including the inherent ability to appropriately stimulate one of the rst lines of defense, known as the innate immune response. In target populations with impaired immune systems, or when the targeted pathogen is complex, this feature may take on added signi cance due to the inability to trigger early protective immune responses. e combination of reduced immunogenicity of puri ed antigens and an increased awareness of the fact that a subset of the general population that is intended to bene t from vaccination may be inherently unequipped to do so has led to recognition of the need for safe and potent immunologic adjuvants that can act as replacements for the original pathogens’ danger signals to trigger, direct, and enhance vaccine-speci c immunity.

Gaston Ramon discovered in 1925 that adding substances such as bread crust or tapioca to diphtheria toxoid in a vaccine formulation increased immune responses against the toxoid. One year later, in 1926, Alexander Glenny reported that administering diphtheria toxoid formulated with potassium aluminum sulfate (alum) induced better antibody responses than soluble antigen alone.

Ever since, aluminum salts have been the most widely used vaccine adjuvant approved for human use. More than 70 years passed before a vaccine containing a new adjuvant (MF59) was introduced in several countries in an in uenza vaccine. When used as adjuvants, aluminum salts can be safe and e ective vaccine components. Since the introduction of aluminum

salts in vaccines, increased knowledge in immunology and host-pathogen interaction, as well as access to new produc- tion technologies, has led to a more accurate selection of the appropriate antigen(s); development of a theoretical framework for the mode of action of several adjuvants, such as Toll-like receptor (TLR) agonists and aluminum salts; and a better understanding of host-pathogen interaction. e knowledge gained and the recognition of the fact that di erent adjuvants may be required to elicit a speci c immune enhancement have led to a resurgence of interest in adjuvants.

page 74 THE JORDAN REPORT 2012

For questions 1-2, refer to the article on page 74 of the current edition (2012) of the Jordan Report:

Identify four (4) secondary observations and two (2) primary observations reported by the authors of this article.

Provide a matching reference citation for each of the six (6) observations you identified in (1) above using the correct APA format and ensuring that a Secondary observation is matched with its Secondary reference and a Primary observation is matched with its Primary reference.

Explanation / Answer

1) To attain established objective of immunogenic, selection or designing a composition of adjuvants

2) Adjuvants in vaccines leads to work innate immunity

3) use of defined TLR ligands as an adjuvants.

4)Important role of adjuvants in modern vaccines. Developement of recent vaccines targeting infectious diseases such as human papillomavirus.

5) adjuvants to improve the immune response, unmet need in modern vaccinology.

6) Adjuvants making vaccines immunogenic

citation:

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