A Review on The Clinical Efficacy of Antitetanic Hyperimmune Serum Prepared in Equine ‎Using Freund Adjuvants in Response to Toxoid and Toxin Immunization

In the industrialized world, tetanus is now a rare disease. However, it is still one of the most dramatic and internationally widespread diseases and a leading cause of death worldwide, with a high case fatality rate, particularly in underdeveloped countries. Immunization to tetanus is antibody-mediated and can be accomplished with tetanus toxoid to elicit an active immunization by forming antitoxin. Consequently, injection of antitetanic hyperimmune serum containing antitoxin can provide passive immunity in those who have a wound that is at high risk and have not been fully vaccinated with tetanus toxoid making it one of the most frequently used treatment agents for tetanus. The production of hyperimmune serum with an adequate neutralizing potency to tetanus is influenced by many factors including adjuvants. Adjuvants are elements that capable of enhancing the antigen-specific immune responses and have proven to be key components in vaccines. Adjuvants come in a variety of forms, each with its own mechanism of action and the immune response elicited by variable making selection of the appropriate adjuvant is a critical issue. Freund's adjuvant is perhaps one of the most commonly used adjuvants that is used as an immunopotentiator (booster) to trigger a humoral antibody response to produce high titer antibodies. There are two types of Freund adjuvants: complete and incomplete.If it contains killed Mycobacterium tuberculosis it is known as Complete Freund Adjuvant (CFA). Without the bacteria it is Incomplete Freund Adjuvant (IFA).  Both CFA and IFA are particularly effective adjuvants in producing high-tittered specific antibody but also each of them has its own advantages and disadvantages. Although the efficacy of Freund adjuvants in triggering the humoral immune response and production of high titer antibodies has been proven, there are several concerns that the use of these adjuvants particularly CFA is associated with significant pathological lesions including severe pain at the injection site, abscesses, chronic granulomas, and ulcerating tissue necrosis. However, many recommendations have been published and highlight the necessity of considering factors like the mode of action of adjuvant,  antigen's size and composition, the species being immunized, the immunization method and the type of immunity required to help selecting the appropriate adjuvant and thus to mitigate some of these concerns. Considering the numerous applications of hyperimmune serum in research and clinical fields, the production of hyperimmune serum as a biological reagent will continue to be developed and thus will continue to require the use of adjuvants with continuing concerns about them. Therefore, a greater understanding of their adjuvanticity potential, safety tolerability, and efficacy could help to limit, control, and correct adjuvant-related side effects making them useful products in the vaccine industry and also could help in the creation of new adjuvants that can be used in vaccines against challenging pathogens.