Immunoadjuvant

In immunology, an adjuvant is a substance that potentiates and/or modulates the immune responses to an antigen to improve them. The word 'adjuvant' comes from the Latin word adiuvare, meaning to help or aid. 'An immunologic adjuvant is defined as any substance that acts to accelerate, prolong, or enhance antigen-specific immune responses when used in combination with specific vaccine antigens.' In immunology, an adjuvant is a substance that potentiates and/or modulates the immune responses to an antigen to improve them. The word 'adjuvant' comes from the Latin word adiuvare, meaning to help or aid. 'An immunologic adjuvant is defined as any substance that acts to accelerate, prolong, or enhance antigen-specific immune responses when used in combination with specific vaccine antigens.' In the early days of vaccine manufacture, significant variations in the efficacy of different batches of the same vaccine were correctly assumed to be caused by contamination of the reaction vessels. However, it was soon found that more scrupulous cleaning actually seemed to reduce the effectiveness of the vaccines, and that some contaminants actually enhanced the immune response. There are many known adjuvants in widespread use, including aluminium salts, oils and virosomes. Adjuvants in immunology are often used to modify or augment the effects of a vaccine by stimulating the immune system to respond to the vaccine more vigorously, and thus providing increased immunity to a particular disease. Adjuvants accomplish this task by mimicking specific sets of evolutionarily conserved molecules, so called PAMPs, which include liposomes, lipopolysaccharide (LPS), molecular cages for antigen, components of bacterial cell walls, and endocytosed nucleic acids such as double-stranded RNA (dsRNA), single-stranded DNA (ssDNA), and unmethylated CpG dinucleotide-containing DNA. Because immune systems have evolved to recognize these specific antigenic moieties, the presence of an adjuvant in conjunction with the vaccine can greatly increase the innate immune response to the antigen by augmenting the activities of dendritic cells (DCs), lymphocytes, and macrophages by mimicking a natural infection. There are many adjuvants, some of which are inorganic (such as alum), that also carry the potential to augment immunogenicity. Two common salts include aluminium phosphate and aluminium hydroxide. Aluminium salts are the most commonly-used adjuvants in human vaccines. Their adjuvant activity was described in 1926. The precise mechanism of alum action remains unclear but some insights have been gained. For instance, alum can trigger dendritic cells (DC) and other immune cells to secrete interleukin-1β (IL-1β), an immune signal that promotes antibody production. Alum adheres to the cell’s plasma membrane and rearranges certain lipids there. Spurred into action, the DC picks up the antigen and speeds to a lymph node, where it sticks tightly to a helper T cell and presumably induces an immune response. A second mechanism depends on alum killing immune cells at the injection site although researchers aren’t sure exactly how alum kills these cells. It has been speculated that the dying cells release DNA which serves as an immune alarm. Some studies found that DNA from dying cells causes them to adhere more tightly to helper T cells which ultimately leads to an increased release of antibodies by B cells. No matter what the mechanism is, alum is not a perfect adjuvant because it does not work with all antigens (e.g. malaria and tuberculosis). Freund's complete adjuvant is a solution of inactivated Mycobacterium tuberculosis in mineral oil developed in 1930. It is not safe enough for human use. A version without the bacteria, that is only oil in water, is known as Freund's incomplete adjuvant. It helps vaccines release antigens for a longer time. Despite the side effects, its potential benefit has led to a few clinical trials. Squalene is a naturally-occurring organic compound that is used in human and animal vaccines. Squalene is an oil, made up of carbon and hydrogen atoms, produced by plants and is present in many foods. Squalene is also produced by the human liver and present in human sebum. MF59 is an oil-in-water emulsion of squalene adjuvant used in some human vaccines. Over 22 million doses of a vaccine with squalene have been administered with no safety concerns. The plant extract QS21 is a liposome made up of plant saponins. It is a part of the Shingrix vaccine approved in 2017.