Vaccine Adjuvants: from 1920 to 2015 and Beyond

Abstract

The concept of stimulating the body’s immune response is the basis underlying vaccination. Vaccines act by initiating the innate immune response and activating antigen presenting cells (APCs), thereby inducing a protective adaptive immune response to a pathogen antigen. Adjuvants are substances added to vaccines to enhance the immunogenicity of highly purified antigens that have insufficient immunostimulatory capabilities, and have been used in human vaccines for more than 90 years. While early adjuvants (aluminum, oil-in-water emulsions) were used empirically, rapidly increasing knowledge on how the immune system interacts with pathogens means that there is increased understanding of the role of adjuvants and how the formulation of modern vaccines can be better tailored towards the desired clinical benefit. Continuing safety evaluation of licensed vaccines containing adjuvants/adjuvant systems suggests that their individual benefit-risk profile remains favorable. Adjuvants contribute to the initiation of the innate immune response induced by antigens; exemplified by inflammatory responses at the injection site, with mostly localized and short-lived effects. Activated effectors (such as APCs) then move to draining lymph nodes where they direct the type, magnitude and quality of the adaptive immune response. Thus, the right match of antigens and adjuvants can potentiate downstream adaptive immune responses, enabling the development of new efficacious vaccines. Many infectious diseases of worldwide significance are not currently preventable by vaccination. Adjuvants are the most advanced new technology in the search for new vaccines against challenging pathogens and for vulnerable populations that respond poorly to traditional vaccines.

Immunological effects of adjuvants, their mechanisms, and relevance to vaccine safety

“…In 1926, French veterinarian Gaston Ramon reported that by injecting starch, breadcrumbs, or tapioca, he managed to induce sterile abscesses at the site of injection with an inactivated toxin, which led to increased anti-sera production, confirming the hypothesis that substances able to induce local inflammation at the injection site were also able to enhance anti-sera yield (1). A few years later, British scientist Alexander Glenny discovered the immune-enhancing effects of aluminium salts (8).…”

“…Since the development of toxoid vaccines in the early 20 th century, scientists were searching for a way to enhance immunogenicity of non-living vaccines (1). Some of the first adjuvants discovered back then, on empirical basis of trial and error, are still in widespread use today, but only recently some light on the molecular mechanisms of their action has been shed.…”

Influenza immunization during pregnancy: Benefits for mother and infant

“…30 Attempts have been made to use adjuvants to improve influenza vaccine immunogenicity, increase breadth of protection and enable antigen dose sparing, 31,32 with some of these adjuvanted vaccines having also been administered to pregnant women. Adjuvanted influenza vaccines currently available in Europe, contain MF59 Ò (Novartis) or AS03 (GlaxoSmithKline, GSK Biologicals) adjuvants.…”

Bioprospecting and their Role in the Innovation of Vaccine Adjuvants: Mega Diversity as a Source of Competitiveness

“…Adjuvants act as immunopotentiators, increasing antigen presentation and improving the response to the vaccine ( Figure 1) [5]. In addition, adjuvants can be been used to improve immune responses in populations with conditions that cause an inadequate response to vaccination, as patients with renal disease [6].This topic is an important research field due to immunization with purified protein antigens typically results in the induction of a modest antibody response with little or no T cell response. Is necessary the search and development of new vaccine adjuvants for improve the protection against infectious diseases in humans and animals, this strategy should have the ability of prevent the infectious disease spread and zoonoses presence, improving the quality of life of the population [7].…”