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Role of Adjuvants in Immunology
Substances that are capable of enhancing the response of the immune system to the antigen are termed as Adjuvants. They can also be substances that enhance the effect of a drug on the body. The history of Adjuvant can be traced back to 1920s, when French biologist, Gaston Ramon revealed that the response of antitoxins to tetanus and diphtheria was amplified by injection of these vaccines, along with other substances such as lecithin, agar, starch oil, saponin, and breadcrumbs. Adjuvants are mainly utilized in organisms that are used to raise antibodies by injecting the antigen. The net effect is to stimulate a larger and more prolonged generation of the antibody.

Adjuvants exercise their action in various ways. Some Adjuvants retain the antigen and so present the antigen to the immune system over a long period of time as the immune response does not occur all at the same time, but relatively is continuous over a longer period. An Adjuvant also by itself can react with some of the cells of the immune system and this interaction may fuel the immune cells for heightened reaction. Adjuvants can also increase the recognition and ingestion of the antigen by the phagocyte. This increased phagocytosis presents more antigens to the other cells that form the antibody.

Adjuvants are chemically greatly heterogeneous set of compounds having a common ability of enhancing the immune response. The Adjuvants such as aluminium phosphate, aluminium hydroxide and calcium phosphates are commonly utilized for human use. Other varieties of adjuvants include cholesterol, endotoxins, aliphatic amines, fatty acids, gram-negative bacteria or products derived from bacteria, liposomes and vegetable oils. In the recent years compounds such as SAFs (syntax adjuvant formulations consisting of muramyl dipeptide or threonyl derative), ISCOMs with Quil-A, and monophosphoryl lipid A are under evaluation for utilization in human vaccine.

Immunopotentiators or vaccine Adjuvants have gained plentiful consideration as important ingredients of vaccine for the current and future. At present times in most of the countries worldwide aluminium salts (alum) remains as the only approved adjuvant for human use with few exceptions.
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New research on vaccine adjuvants

The original article in this thread outlines the importance of adjuvants in enhancing vaccine effectiveness. In maximising the immunogenicity of vaccines, an effective adjuvant can allow the dose or number of administrations of the vaccine to be reduced, thus making the whole process more cost-effective and helping overcome issues associated with limited worldwide availability of various vaccines.

As mentioned, aluminium-containing adjuvants are the most commonly used in human vaccines. Despite this, the mechanisms of action of these adjuvants are not well understood. A study from Purdue University in the USA looked at kinetics of the inflammatory response in mice after intramuscular injection of an aluminium adjuvant. They found that in naïve mice, inflammatory cells accumulated at the injection site within 2-6 hours, at first dominated by neutrophils, with later accumulation of macrophages, eosinophils and antigen-presenting cells. In previously immunised mice, the accumulation of macrophages, eosinophils and antigen-presenting cells was more rapid and robust and coincided with accumulation of chemokines.

Research is on-going to identify other effective, novel adjuvants. In a study on rhesus macaques from Merck Research Laboratories in Pennsylvania in the USA, a saponin-based adjuvant called ISCOMATRIXTM was found to be more effective than either aluminium hydroxylphosphate sulphate or a synthetic TLR9 agonist as an adjuvant for a novel rabies vaccine. This is relevant in the context of worldwide supply issues of rabies vaccine.

Another study from Universidad Nacional Autónoma de México examined a novel synthetic peptide GK-1, derived from Taenia crassiceps fused to the pVIII protein of a heat-inactivated phagemid vector (FGK1) as an adjuvant when co-administered to mice or pigs with influenza vaccine. They found that in pigs, for example, one dose of FGK1 and influenza vaccine induced comparable serum levels of IgG anti-influenza to two doses of influenza vaccine alone. This peptide fusion is a potentially low-cost adjuvant and is currently in testing for veterinary purposes.

A third study from Shandong University in China evaluated dendritic cell vaccines for cervical cancer. Dendritic cells were loaded with human papillomavirus type 16 (HPV16) peptides and administered with a CpG oligodeoxynucleotide (CpG-ODN) as adjuvant. In vivo mice studies and in vitro studies gave encouraging results in terms of immunogenicity as assessed by IL-12 levels, the allogeneic T cell-stimulatory capacity and the cytotoxicity of cytotoxic T lymphocytes (CTLs) in vitro and tumour sizes, expression of IgG and IFN-γ, and the presence of human T cells in vivo.

Clearly development of adjuvants is a field with promise for exciting new prospects.


DISTEFANO, D. et al., 2013. Immunogenicity of a reduced-dose whole killed rabies vaccine is significantly enhanced by ISCOMATRIX adjuvant, Merck amorphous aluminum hydroxylphosphate sulfate (MAA) or a synthetic TLR9 agonist in rhesus macaques. Vaccine, 31(42), pp. 4888-4893

LU, F. and HOGENESCH, H., 2013. Kinetics of the inflammatory response following intramuscular injection of aluminum adjuvant. Vaccine, 31(37), pp. 3979-3986

SEGURA-VELÁZQUEZ, R. et al., 2013. Influenza vaccine: development of a novel intranasal and subcutaneous recombinant adjuvant. Vaccine, 31(37), pp. 4009-4016

WANG, H.L. et al., 2013. In vitro and in vivo evaluations of human papillomavirus type 16 (HPV16)-derived peptide-loaded dendritic cells (DCs) with a CpG oligodeoxynucleotide (CpG-ODN) adjuvant as tumor vaccines for immunotherapy of cervical cancer. Springer Verlag.
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The Immunization with Adjuvants can be used for a variety of purposes and some of them are listed here:
• It is to improve the immunogenicity of highly purified or recombinant antigens (protein or peptide).
• It is to trim down the quantity of antigen or the number of immunizations needed for protective immunity.
• It is to get better the efficacy of vaccines in newborns, the aged or immuno-compromised persons and
• As an antigen release systems for the uptake of antigens by the human mucosa

The difficulty with highly pure recombinant or synthetic antigens used in modern day vaccines is that they are usually far less immunogenic than older style live or killed complete organism vaccines. This has fashioned a major need for enhanced and more influential adjuvants for use in these vaccines. With a small number of exceptions, alum remains the sole adjuvant approved for human use in the majority of countries worldwide. Although alum is able to induce good antibody (Th2) production immunity, it has modest aptitude to stimulate cellular (Th1) immune responses which are so imperative for protection against many pathogens. In addition, alum has the potential to cause severe restricted but systemic side-effects including sterile abscesses, eosinophilia and myofascitis, even though fortunately a large number of the more serious side-effects are quite rare. There is also a community apprehension regarding the possible function of aluminium in neurodegenerative diseases such as Alzheimer's disease. Consequently, there is a major unmet necessitating for safer and more effective adjuvants appropriate for human use. In particular, there is demand for safe and non-toxic adjuvants capable 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 extremely specialized with their own and only one of its kind needs in respect of suitable adjuvant technology.
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