About Adjuvants
Adjuvants as Stabilizing Agents
Although Immunological Adjuvants have traditionally been viewed as substances that aid the immune response to antigen, i.e. irritants, adjuvants have also evolved as substances that can aid in stabilizing formulations of antigens, especially for vaccines administered for animal health. Currently in the United States there are between 60 and 80 billion doses of vaccine produced for animal health each year, with livestock receiving the vast majority of these doses.1 It is estimated that this number is 2-3 times that level for the rest of the world, which provides an estimated 120 to 180 billion doses of vaccine per year for animal health. The primary reason for this large number is that the meat producing animals (especially poultry, fish and crustaceans) are raised in highly populated and condensed farming operations and vaccines are administered en mass to control and mitigate disease. Each year the meat producing animals turn over providing a new group of production livestock animals that will require health care to manage infectious disease and nutrition. Thus, the animal health vaccine manufacturers hold a large body of information of the number and type of adjuvants used for aid in eliciting an immune response and in stabilizing vaccine preparations.
In addition to the shear number of doses administered each year, animal health vaccines often contain more than one antigen comprising both modified live and inactivated preparations of different biological pathogens. The primary reason is that animals raised for meat production used by the world human population are afflicted by similar types of diseases that affect the human population, including pathogens that cause respiratory, reproductive, immunodeficiency, circulatory, and enteric clinical manifestations. As a consequence, the formulation of multivalent vaccines with adjuvant must also meet stability requirements for storage and shelf life.
Multivalent vaccines provide a labor savings management alternative to livestock producers by reducing the number of times an animal may need treated. Also, animal vaccines are administered where cold chain support may not be available such as a paddock, loading chute, nursery, or hatching facility. Thus, the economic pressures to keep prophylactic health costs low, result in continuous efforts by global animal health vaccine manufacturers to find the most efficient process methods to grow and formulate biological pathogens. As a consequence animal health pathogens are often harvested with the minimum amount of downstream processing performed before they are filled, formulated and assembled. This results in a higher total macromolecular mass in animal vaccines than human vaccines. Fully assembled (adjuvanted) vaccine serials can also be used as sources for Master Reference in product release testing. As such, adjuvanted products must meet certain stability reqirements under long term storage conditions.2 Thus, stability is an important feature when considering formulation with adjuvants for animal vaccine manufacturers.
1. CVB Notice 77. Veterinary Biological Products Produced in Licensed Establishments Produced and Destroyed 01/01/09 through 31/12/09.
2. Veterinary Services Memorandum (VSM) 800.90. Guidelines for Veterinary Biological Relative Potency Assays and Reference Preparations Based on ELISA Antigen Quantification (August 5, 1998)