Homogenization Application: Vaccine Adjuvants

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Deb Shechter
Sep 28, 2015
min read
Homogenization Application: Vaccine AdjuvantsHomogenization Application: Vaccine AdjuvantsHomogenization Application: Vaccine Adjuvants

Every year, 2.5 million human lives are preserved due to effective vaccination delivery (1). The 2014 Ebola outbreak is still fresh as wet paint; between Guinea, Liberia and Sierra Leone, at least 11,291 lives were taken before introduction of VSV-EBOV. After its introduction, the region’s Ebola death toll was nearly extinguished. As researchers and developers of this essential product, it is our responsibility to ensure that vaccine composition is both safe and efficacious for the consumer. This starts with a critical look at the vaccine adjuvant you are using. Following is a synopsis of three well-known adjuvants, intended to inform your company’s vaccine protocols and/or introduce you to alternatives you may not yet be familiar with. (2)

  1. Aluminum - Introduced in 1926, aluminum is the most commonly used adjuvant, having seen great success in human vaccinations such as tetanus and diphtheria. The term encompasses several types of insoluble preparations that can directly capture the antigen, such as aluminum hydroxide, aluminum phosphate, and aluminum potassium sulfate (alum). Aluminum salts stimulate a T helper 2 (Th2) immune response; this elicits a different mechanism of action than adjuvants that induce a T helper 1 (Th1) response, specifically in that Th2 cells mediate B cell differentiation. Preparation involves exposing aluminum ions (e.g. sulfates or chlorides) in aqueous solutions to alkaline conditions. Although its efficacy has been well established in over 60 years of use, recent concerns around its safety have spurned conflicting results, with the FDA citing its safety (3). Yet others, such as the National Vaccine Information Center, claim that the presence of aluminum interferes with cellular and metabolic processes, especially among children. (4)
  1. Freund’s Adjuvant, Complete & Incomplete - Named for its discoverer Jules T. Freund, Freund’s Adjuvant comes in two forms, both of which are comprised of a water-in-oil emulsion prepared through homogenization. If the emulsion contains mycobacteria (usually M. tuberculosis) it is classified as Complete Freund’s Adjuvant; Incomplete Freund’s Adjuvant is distinct solely in that it does not contain mycobacteria. Because the mycobacteria in Complete Freund’s Adjuvant attracts macrophages and other cells to the injection site, this form elicits a heightened Th1 immune response. Thus, Complete Freund’s Adjuvant is used for the initial injection while Incomplete Freund’s Adjuvant is used for boosters. Incomplete Freud’s Adjuvant works by stimulating a distinct Th2 immune response. Because of the strong initial immune reaction, Freund’s Adjuvant often causes granulomas at the injection site, which is one of the central drawbacks to this option. (5, 6)
  1. Monophosphoryl lipid A (MPLA) - MPLA was developed as a low-toxicity derivative to lipopolysaccharide (LPS), a highly toxic component of Gram-negative bacterial cell walls. Lipid A, the anchor portion of LPS, is responsible for eliciting a strengthened Th1 immunological response. MPLA is unique in that it is one of the first Toll-like receptor agonists being used in human vaccinations, and also holds promise for incurring few side effects. (7)

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