Rational Design and In Vivo Characterization of Vaccine Adjuvants

Abstract

Many different adjuvants are currently being developed for subunit vaccines against a number of pathogens and diseases. Rational design is increasingly used to develop novel vaccine adjuvants, which requires extensive knowledge of, for example, the desired immune responses, target antigen-presenting cell subsets, their localization, and expression of relevant pattern-recognition receptors. The adjuvant mechanism of action and efficacy are usually evaluated in animal models, where mice are by far the most used. In this review, we present methods for assessing adjuvant efficacy and function in animal models: (1) whole-body biodistribution evaluated by using fluorescently and radioactively labeled vaccine components; (2) association and activation of immune cell subsets at the injection site, in the draining lymph node, and the spleen; (4) adaptive immune responses, such as cytotoxic T-lymphocytes, various T-helper cell subsets, and antibody responses, which may be quantitatively evaluated using ELISA, ELISPOT, and immunoplex assays and qualitatively evaluated using flow cytometric and single cell sequencing assays; and (5) effector responses, for example, antigen-specific cytotoxic potential of CD8 + T cells and antibody neutralization assays. While the vaccine-induced immune responses in mice often correlate with the responses induced in humans, there are instances where immune responses detected in mice are not translated to the human situation. We discuss some examples of correlation and discrepancy between mouse and human immune responses and how to understand them.

Vaccine development for bacterial pathogens: Advances, challenges and prospects

“…This is important, especially for protein-based vaccines [43]. Adjuvants in vaccine production facilitate the induction of adequate immune response in place of an antigen [216,217]. Recently, Cibulski et al [218] reported QB-90, a Quillaja brasiliensis leaf saponin fraction, stimulating a systemic immune response and promoting a local and transient immune response in mice model when administered up to 24 h before the administration of antigen.…”

Head-to-Head Comparison of Novel Vaccine Technologies Comes with a Minefield of Challenges

“…Finally, a higher antigen dose can lead to greater production of the follicular helper T cells that govern the germinal center responses [ 27 ]. These are, however, speculations that need to be proven using in vivo tracking studies: for example, using radio- or fluorescently labeled proteins as described in [ 28 ]. It should be noted that it cannot be used as a general rule that depot formation at the site of injection is a prerequisite for a strong T cell response, clearly illustrated by GLA-SE [ 29 ] and AS01 [ 30 ], these being two non-depot-forming adjuvants both documented to induce durable Th1 responses.…”

Developing New Anti-Tuberculosis Vaccines: Focus on Adjuvants

“…This type of vaccines overcomes some of the safety concerns associated with live attenuated or inactive vaccines [ 10 ]. Furthermore, as they are designed using specific antigens, they can be targeting different aspects of the infection, optimized as the research progresses and provide additional immune responses for more complex pathogens, such as Mtb [ 8 , 11 ].…”

“…While being very safe, subunit vaccines cannot rely solely on the antigen to achieve a desired effect as they are generally poorly immunogenic [ 10 ]. Adjuvants are needed in their formulation in order to increase immunogenicity, decrease the antigen dose, ensure a targeted delivery and optimize the antigens interaction with the immune cells [ 10 , 11 ]. Undeniably, adjuvants are an important part of new subunit vaccines design and in general, adjuvants identification, design and characterization is essential to modern vaccines formulation [ 12 ].…”