Vaccine adjuvants for infectious disease in the clinic

Abstract

Adjuvants, materials added to vaccines to enhance the resulting immune response, are important components of vaccination that are many times overlooked. While vaccines always include an antigen to tell the body what to vaccinate to, of equal importance the adjuvant provides the how, a significant factor in producing a complete response. The adjuvant space has been slow to develop with the first use of an adjuvant in a licensed vaccine occurring in the 1930s, and remaining the only adjuvant in licensed vaccines for the next 80 years. However, with vaccination at the forefront of protection against new and complex pathogens, it is important to consider all components when designing an effective vaccine. Here we summarize the adjuvant space in licensed vaccines as well as the novel adjuvant space in clinical trials with a specific focus on the materials utilized and their resulting impact on the immune response. We discuss five major categories of adjuvant materials: aluminum salts, nanoparticles, viral vectors, TLR agonists, and emulsions. For each category, we delve into the current clinical trials space, the impact of these materials on vaccination, as well as some of the ways in which they could be improved. Adjuvants present an exciting opportunity to improve vaccine responses and stability, this review will help inform about the current progress of this space.

Translational impact statement: In the aftermath of the COVID-19 pandemic, vaccines for infectious diseases have come into the spotlight. While antigens have always been an important focus of vaccine design, the adjuvant is a significant tool for enhancing the immune response to the vaccine that has been largely underdeveloped. This article provides a broad review of the history of adjuvants and, the current vaccine adjuvant space, and the progress seen in adjuvants in clinical trials. There is specific emphasis on the material landscape for adjuvants and their resulting mechanism of action. Looking ahead, while the novel vaccine adjuvant space features exciting new technologies and materials, there is still a need for more to meet the protective needs of new and complex pathogens.

Keywords: Adjuvants; FDA; clinic; clinical trials; immune response; infectious diseases; vaccines.

FIGURE 1

Adjuvants in licensed vaccines in the current clinical trial space. (a) The classification of unique vaccine formulations evaluated in clinical trials by adjuvant licensure status in which a unique vaccine formulation is defined by a distinct combination of adjuvant and antigen among the trial space. Each section displays the unique vaccine formulation count and that percentage of the whole. (b) The number of clinical trials that contain an adjuvant in a licensed vaccine displayed as the number of trials in which this adjuvant is utilized in a unique vaccine formulation and the number of trials in which the adjuvant is utilized in a repeat vaccine formulation.

FIGURE 2

Number of clinical trials by adjuvant category. This is represented as both trials containing a unique vaccine formulation and those containing repeat formulations.

FIGURE 3

Nanoparticle adjuvants in the clinic. (a) Make‐up of unique vaccine formulations containing nanoparticle adjuvants in the clinical trial space separated by nanoparticle type: lipid nanoparticles, Matrix‐M, betulin nanoparticle (NP), gold nanoparticle (GNP), nanostructured lipid carriers (NLC), and lipid inorganic nanoparticles (LION). The number of unique vaccine formulations as well as the resulting percent of the whole space is provided. (b) The number of clinical trials that contain a lipid nanoparticle by responsible party of the clinical trial. This is defined by both number of trials with unique vaccine formulations and number of trials with repeat formulations.

FIGURE 4

Viral vectors in the clinic. (a) Make‐up of unique vaccine formulations containing viral vectors in the clinical trial space separated by viral family. The number of unique vaccine formulations as well as the resulting percent of the whole space is provided. (b) The number of clinical trials that contain an adenovirus vector by serotype. This is defined by both number of trials with unique vaccine formulations and number of trials with repeat formulations.

FIGURE 5

TLR Agonists in the clinic. (a) The number of clinical trials that contain a TLR agonist by TLR number. This is defined by both number of trials with unique vaccine formulations and number of trials with repeat formulations. (b) Make‐up of unique vaccine formulations containing a TLR agonist in the clinical trial space divided by TLR agonist type and further specified by the agonist utilized. The number of unique vaccine formulations as well as the resulting percent of the whole space is provided.

FIGURE 6

Make up of unique vaccine formulations that utilize a TLR agonist divided by the combination material it is formulated with. The number of unique vaccine formulations as well as the resulting percent of the whole space is provided.