Vaccine adjuvants: Current state and future trends

Abstract

SummaryThe problem with pure recombinant or synthetic antigens used in modern day vaccines is that they are generally far less immunogenic than older style live or killed whole organism vaccines. This has created a major need for improved and more powerful adjuvants for use in these vaccines. With few exceptions, alum remains the sole adjuvant approved for human use in the majority of countries worldwide. Although alum is able to induce a good antibody (Th2) response, it has little capacity to stimulate cellular (Th1) immune responses which are so important for protection against many pathogens. In addition, alum has the potential to cause severe local and systemic side-effects including sterile abscesses, eosinophilia and myofascitis, although fortunately most of the more serious side-effects are relatively rare. There is also community concern regarding the possible role of aluminium in neurodegenerative diseases such as Alzheimer's disease. Consequently, there is a major unmet need for safer and more effective adjuvants suitable for human use. In particular, there is demand for safe and non-toxic adjuvants able to stimulate cellular (Th1) immunity. Other needs in light of new vaccine technologies are adjuvants suitable for use with mucosally-delivered vaccines, DNA vaccines, cancer and autoimmunity vaccines. Each of these areas are highly specialized with their own unique needs in respect of suitable adjuvant technology. This paper reviews the state of the art in the adjuvant field, explores future directions of adjuvant development and finally examines some of the impediments and barriers to development and registration of new human adjuvants.

Efficient Immunization and Cross-Priming by Vaccine Adjuvants Containing TLR3 or TLR9 Agonists Complexed to Cationic Liposomes

“…The only vaccine adjuvants currently licensed for use in humans (aluminum hydroxide, salts, MF59, and virosomes) augment immune responses largely through enhancing Ag delivery (6,7). Both aluminum hydroxide and MF59 stimulate primarily humoral immune responses (8).…”

Interleukin-6 has differential influence on the ability of adjuvant formulations to potentiate antibody reponses to a Plasmodium falciparum blood-stage vaccine

“…Adjuvants have known to affect vaccineinduced immune responses in terms of magnitude; types of immunity, eg. TH1/TH2, CTL, antibodies (reviewed in [1][2][3]; as well as the specificity of epitope recognition [4][5][6]. On the other hand, the immunological background of the host may have reciprocal effects on the activities of vaccine adjuvants, which in turn may influence efficacy.…”

Vaccines against Toxoplasma gondii: challenges and opportunities

“…Adjuvants have generally been defined as substances that enhance the immunogenicity of the antigenic vaccine components. Adjuvants have been categorised into three groups, (i) active immunostimulants, (ii) carrier proteins that provide T cell help or (iii) vehicle adjuvants such as emulsions and vesicles that serve as a matrix for antigens, as well as stimulate the immune response (Petrovsky & Aguilar 2004). However, as components of experimental vaccines have become increasingly refined, often to the point of single proteins or small peptides, a fundamental immunological role has emerged for vaccine adjuvants consistent with category (i).…”