Adjuvants are substances which when mixed with an antigen enhance the immunogenicity of that antigen are often used to boost the immune response. Some adjuvants prolong the persistence of antigen in the immunized animals. For example, when an antigen is mixed with aluminum potassium sulfate (alum), the salt precipitates the antigen resulting in a slower release of antigen from the injection site. Freund’s water in oil adjuvants also function in this way. Freund’s complete adjuvant, which contains heat killed Mycobacteria in the water in oil emulsion, is more potent than the incomplete form because a muramyl dipeptide component of the mycobacterial cell wall activates macrophages, increasing production of interleukin 1 and thus augments the immune response by activating THcells.
Adjuvants areare often used to boost the immune response. Unlike attenuated live vaccines, killed whole organism generally require the addition of an adjuvant to be effective. Some of the features involved in adjuvant selection are the antigen, the animal species to be vaccinated, the route of administration and the likelihood of side effects (Aguilar, Vaccine 25, 2007, 3752-3762).
Vaccine developers have relied on adjuvants for over 90 years, since the serendipitous discovery of teh immune enhancing effects of aluminum salts. For most of the twentiether centry, aluminum was the only adjuvant included in licensed vaccines. Today, modern adjuvants are designed to overcome twenty-first centruy vaccine challengers. With the introduction of new moleuels, adjuvant formulation now focuses on micro and nanoparticulate platforms, including ano-alum; emulsion or Pickering emulsion; liposomes and combiantion adjuvants sucha s ISCOMS, AS04 and PLG. (Xinhao Ye, “Increasing vaccine efficacy with novel adjuvants” Genetic Engineering & Biotechnology News, September 2024).
The FDA has approved six adjuvants for use in human vaccines: aluminum, MF59, AS04, AS03, AS01 and Cpg ODN. Selecting the right adjuvant can elicit an immune response tailored to specific pathogens. (Xinhao Ye, “Increasing vaccine efficacy with novel adjuvants” Genetic Engineering & Biotechnology News, September 2024).
Specific Types of Adjuvants
Aluminum salts (aluminum hydroxide, aluminum phosphate or alum): Some adjuvants prolong the persistence of antigen in the immunized animals. For example, when an antigen is mixed with aluminum potassium sulfate (alum), the salt precipitates the antigen resulting in a slower release of antigen from the injection site. Aluminum adjuvants are widely used in human and veterinary vaccines. They are appropriate adjuvants for vaccines that confer protection by inducing antibodies via the induction of a type 2 immune response, but they do not induce cytotoxic T cell and cell mediated immunity (HogenEsch, Vaccine, 20 (2002), S34-S39.
Currently used vaccines with aluminum as the adjuvant include Biotrax, Engerix-B, Recombivax HB, Gardasil 9, Covid-19. (Xinhao Ye, “Increasing vaccine efficacy with novel adjuvants” Genetic Engineering & Biotechnology News, September 2024).
–AS04 is a monophoshoryl lipid A (MPL) + aluminum salt approved adjuvant. (Xinhao Ye, “Increasing vaccine efficacy with novel adjuvants” Genetic Engineering & Biotechnology News, September 2024).
Oil in water composed of squalene (MF59): increases antigen-presenting cells, cruitment and activation and promotes anitgen uptake and migration of cells to lymph nodes.
Tocopherol, squalene and polysorbate 80: promotes local production of cytokines and recuitment of innate cells. It is used in the approved Pandemrix vaccine.
MPL and QS-21, a natural extract of Cilean soapbark tree (AS01): elicits IL1beta and IL-1beta release in antigen presenting cells when co-stimulated with MPLA. It is approved for the Singrix, Mosquirix vaccine.
Cytosine phosphoguanine (CpG ODN): enhances antibody and TH1 responses. I t is approved for the HEPLISAV-B vaccine.
Escherichia coli Enterotoxin: is one of the most powerful mucosal adjuvants known and has ben used to optimize both mucosal and systemic immune response to an inactivated influenza vaccine for parenteral administration (Couch, Nasal Vaccination, N Engl J Med 2004, 350, 860-1).
Freund’s water in oil adjuvants also function in this way.
Freund’s complete adjuvant, which contains heat killed Mycobacteria in the water in oil emulsion, is more potent than the incomplete form because a muramyl dipeptide component of the mycobacterial cell wall activates macrophages, increasing production of interleukin 1 and thus augments the immune response by activating THcells.
Heat shock proteins (HSPs): See also HSP fusion peptides in outline. HSPs have been shown as attractive immunoadjuvants to enhance antigen specific immunity. Vaccination with HSP peptide complexes from autologous tumors or virus infected cells has been shown to eleicity specific antitumor or antivirus immune resposnes. (Zhang J Gene Med 2007, 9: 715-726).
Monophosphoryl lipd A (MPL): is a derviative of the lipopolysacchrides of the bacterial cell wall and has been approved by the European Medicines Agency (EMEA) as the vaccine FENDRIX 9GlaxoSmithKline), a vaccine against hepatitis B. It was developed by Corixa (Seattle, WA) and is an adjuvant in several other vaccines.
Laser Based Vaccine Adjuvants:
Novoselova (Photodermatol Phtoimmunol Photomed 2006, 22(1), 33-8) disclose that laser radiation has been widely used during induction of anti-microbial and anti-virus activity and that low power laser irradiation increased IL-2 and Hsp70 production when applied on the thymus projection area.
Onikienko (US 14/255,931, published as US 2014/0335110) discloses using laser radiation as an adjuvant for vaccine. The composition can further comprise HSP70.