Alum, the most commonly used adjuvant in human vaccines, triggers the release of cytokine in macrophages, more specifically the expression of IL-1β which depends on NLRP3 inflammasome sensor signaling. 

Smith College

Nanomaterials have emerged as promising tools to amplify or suppress host's immune response. By acting as adjuvants added to vaccines for COVID-19, engineered nanomaterials can aid subjects with impaired immune system, such as the elderly, and reduce the amount of vaccine protein production and injection. 


Intranasal delivery of polymer-encapsulated antigen triggers a strong immune response, and the success of vaccination depends on the appropriate type of polymer in combination with the antigen. Similarly, researchers have developed lipid and lipid-based NPs as delivery platforms for mRNAs or siRNAs to enable the synthesis of key viral proteins for vaccination (for example, Moderna’s mRNA-1273/NCT04283461 vaccine) or to inactivate critical viral target genes, respectively. 


Considering the possibility of random viral mutations that may alter the antigen shape, functionalizing nanomaterials with a wide number of molecules at the same time to target the virus, or motifs that are specific for pathogens, will increase the efficiency of vaccines and their ability to prevent viral infection.


There are ongoing screenings and classifications of various nanomaterials based on their immunomodulatory properties and cytotoxicity levels. Developing an adjuvant for clinical use requires Phase III randomized trials, which could take several years.


Nanomaterial-based Immune Modulation for SARS-CoV-2

Weiss C, Carriere M, Fusco L, et al. Toward Nanotechnology-Enabled Approaches against the COVID-19 Pandemic. ACS Nano. 2020;14(6):6383-6406. doi:10.1021/acsnano.0c03697

Toward Nanotechnology-Enabled Approaches against the COVID-19 Pandemic

These licensed adjuvants have already been found to stimulate early STAT1/IRF1 interferon signaling. 

AS01 and AS03 (ASs)

alum

Saponin-based Matrix M is currently in Phase I clinical testing as an adjuvant for SARS-Cov-2 glycoprotein nanoparticle vaccine.

(NCT04368988)

saponin-based Matrix M

Hierarchical carbon materials with tuned porosity have shown to selectively, quickly, and completely adsorb and remove pro-inflammatory cytokines, such as interleukin  (IL)-6 and tumor necrosis factor (TNF)-α, from the blood serum. The fast and complete removal of cytokines associated with cytokine release syndrome (CRS) due to COVID-19 may prevent uncontrolled inflammatory cascade, which increases the risk of acute respiratory distress syndrome (ARDS) and multiple organ failures. 


- graphene with open and accessible surfaces

mesoporous carbon adsorbents with hierarchical structure, tuned pore size, and surface chemistry

This nanomaterial can boost immune response by activating STAT1/IRF1 signaling in monocytes and T cells. This results in the accumulation of T cell chemoattractants and polarization of macrophage 1/T-helper 1 (M1/Th1). 

graphene oxide functionalized with amino groups (GO-NH2)

This functionalized nanodiamond promotes anti-inflammatory response in mice by reducing microphage infiltration of lung capillaries that may lead to difficulties in gas exchange. It also reduced proinflammatory mediators, including iNOS and tumor necrosis factor (TNF)-α. In vitro study found that the nanomaterial can trigger anti-inflammatory response in human macrophages as well.

octadecylamine-functionalized and dexamethasone-adsorbed nanodiamond


SARS-CoV-2 triggers a cytokine storm in the body, known as cytokine release syndrome (CRS), which results from an excessive immune response and leads to severe deterioration of the patient's health. This inflammatory storm often causes  acute respiratory distress syndrome (ARDS), which is often associated with multiple-organ failure, representing the leading causes of death in critical patients. 


Nanomaterials have been exploited to adjust the immune response to an optimized level, and such proprieties might be explored to inhibit cytokine releases. Nanosystems can enhance the specificity/efficiency of immunosuppressant delivery to target immune cells, with consequent reductions in drug dose, drug distribution to non target tissues and organs, and possible side effects. Additionally, specific nanotools can be designed to evade the immune system and enhance the solubility of poorly soluble immunosuppressant agents; the potential of finely tuning their surface charge opens possibilities for encapsulation strategies and offers accommodation for a high drug load.


Using nanocarriers to achieve targeted delivery of immunosuppressive drugs, or the specific and controlled inhibition of only a specific immune cell subpopulation, can play a critical role in limiting complications such as sepsis due to underlying secondary bacterial infections. 


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