Effective vaccine adjuvants

In summary, therefore, a whole range of adjuvants have thus far been identified/developed. Problems of toxicity have precluded the use of many of these adjuvants (particularly in humans). However, research efforts continue in an attempt to develop the next generation of safe and, hopefully, even more effective vaccine adjuvants. 

Synthetic and Natural TLR4 Agonists as Safe and Effective Vaccine Adjuvants... 

CpG ODNs are also effective as vaccine adjuvants to enhance adaptive TH1 cellular immune responses.104 In mice, CpG ODNs can trigger strong TH1 responses,105 enhancing the number and function of tumor-specific Cytotoxic T lymphocytes (CTLs) and IFN-y secreting T cells.106 This has resulted in therapeutic vaccines in mouse tumor models where no other approach has shown comparable efficacy, even with large (1 cm) established tumors.107 108 Even without a vaccine, CpG ODNs can induce CD8+ T cell-mediated regression of established tumors with durable memory responses.109... 

Successful vaccines have several important properties such as safety, effectiveness, low cost per dose, and ease of preparation. Vaccines, whether peptide, protein, or DNA, have limited potency without codelivery with an adjuvant and/or a specialized delivery system (11). There is currently a lack of safe, nontoxic, effective. Food and Drug Administration (FDA)-approved vaccine adjuvants capable of stimulating cellular (Thl) immunity (12). Most potent immune activators are also toxic at relatively low doses and cannot, therefore, be successfully used as adjuvants (12). 

A wide variety of materials have been explored for their adjuvant activity, although not all are equally effective or nontoxic, especially in humans. Alum and other aluminum salts were first recognized in 1926 and remain the most effective agents licensed for human use by the FDA, although some French products also use calcium phosphate. However, in recent years it has become evident that new and improved vaccine adjuvants are needed. 

There is a perceived need to develop effective vaccines against bovine spongiform encephalopathy (BSE) and the human form, new variant Creutzfeldt-Jacob (nvCJ) disease. Organ transplant vaccines would obviously be beneficial and tetanus toxoid has been shown to lower cholesterol in animals. Tumor-specific antigens have also been explored and heat stress proteins have been evaluated as adjuvants in this case. 

MPL Vaccine adjuvant Cardiovascular/respiratory function safety pharmacology study, repeat-dose toxicity in rat (up to 4wks—subcutaneous), rabbit and dog, reproduction (embryo-fetal studies in rat and rabbit) and 2 in vitro genotoxicity studies No adverse effects 40... 

Keyhole limpet hemocyanin (KLH) is an immune stimulant and a hapten carrier, derived from a circulating glycoprotein of the marine mollusk Megathura crenulata. KLH has significant antiproliferative effects in vitro against several types of cancers (23). It has also been conjugated to a variety of immunogens and used as a vaccine adjuvant (24). 

Liposomal formulations may also be used to deliver TLR4 agonists. Consisting of spherical vesicles formed by the self-assembly of phospholipid bilayers, liposomes are a versatile, biocompatible vaccine adjuvant formulation. The wide variety of available phospholipid molecules that are employed to make liposomes may have significant effects on the structure and biological activity of the adjuvant. 

Nanooxides such as fumed silica, titania, alumina, etc. (with spherical primary nanoparticles) are used as fillers for complex drugs, enterosorbents, vaccine adjuvants, food additives, etc.1,2 In general nonporous spherical nanoparticles can adsorb solutes in low amounts because the desolvation effect causes an... 

Since many diseases are associated with cellular immunodeficiency there is an important need for immunostimulants. They have potential use as vaccine adjuvants and for the treatment of cancer, human immunodeficiency viral infections and in certain other infections. The immunostimulating agents are probably best known at this time for their use in the treatment of cancer. When used for this purpose these drugs often act through more than one mechanism. For example, in addition to their ability to augment the immune system, they may have direct cytotoxic effects as well as being able to induce differentiation of the cancer cells. 

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