Freund’s adjuvant is a classic of vaccine adjuvants and the basis of experimental immunology
Authors: Hladkykh F.V. 
Published: November 2024

Background. The invention of vaccines is rightfully considered one of the triumphs of medical research and one of the most remarkable achievements in public health in the history of humanity. According to the World Health Organization, vaccination saves 5 lives every minute and has saved over 25 million lives from 2011 to 2020. The effectiveness of a vaccine depends not only on the components of the antigen but also on the adjuvants, which are often used for more effective stimulation of the immune system.

Purpose – to characterize the modern understanding of vaccine adjuvants, particularly Freund’s adjuvant, as a foundation of experimental immunology based on open source information.

Materials and Methods. The selection of publications was conducted using databases such as PubMed, Clinical Key Elsevier, Cochrane Library, eBook Business Collection, and others, which provided information on vaccine adjuvants, particularly Freund’s adjuvant. In the first stage, a search for literature sources was performed using keywords: vaccine adjuvants, complete Freund’s adjuvant, alum, adjuvant arthritis, experimental immunology. In the second stage, the abstracts of the articles were reviewed, and publications that did not meet the research criteria were excluded. In the third stage, the full texts of the selected articles were examined for compliance with the inclusion criteria and relevance of the studies.

Results. In 1924, G. Ramon demonstrated that the co-administration of the diphtheria anatoxin he had recently developed with other compounds such as tapioca, lecithin, agar, starch oil, saponin, and others enhances antitoxin reactions to diphtheria. In 1942, J. Freund developed a potent adjuvant in the form of a water-in-oil emulsion using mineral oil that contained heat-killed mycobacteria (Mycobacterium tuberculosis), which was named complete Freund’s adjuvant. However, over time, Freund’s adjuvant was banned for use in vaccines for humans due to its toxicity. Despite numerous studies, until 2009, aluminum salts dominated the use of adjuvants in licensed vaccines. Beginning in 2010, the demand for the development of new adjuvants noticeably increased, especially following several pandemics such as Ebola, Zika, and COVID-19. It is known that adjuvants enhance the adaptive immunity of vaccines by activating innate immune cells. The main concept of their effect is that adjuvants promote the production of antigen presentation signals and costimulatory signals by activating antigen-presenting cells. The model of adjuvant arthritis induced by complete Freund’s adjuvant was created to study the pathogenesis of arthritis, including rheumatoid arthritis, gout, and osteoarthritis, as well as to evaluate the effectiveness of certain anti-arthritis and anti-inflammatory drugs.

Conclusions. Vaccine adjuvants encompass a wide range of chemical compounds and substances that enhance immune responses through physical or chemical binding with antigens. The most significant influences on the formation of the modern understanding of vaccine antigens and immunology in the 20th century were Gaston Ramon (1886–1963), Alexander Glenny (1882–1965), and Jules Freund (1890–1960). Complete Freund’s adjuvant has historically been and remains one of the most useful tools for immunologists. The use of antigenic mixtures from biological tissue extracts along with complete Freund’s adjuvant allows for the reproduction of various organ-specific autoimmune diseases in laboratory animals (such as autoimmune arthritis, myocarditis, hepatitis, thyroiditis, encephalomyelitis, etc.), facilitating preclinical studies on the effectiveness of potential immunomodulating and symptomatic therapeutic agents.