Applications of nanomaterials as vaccine adjuvants

Abstract

Vaccine adjuvants are applied to amplify the recipient's specific immune responses against pathogen infection or malignancy. A new generation of adjuvants is being developed to meet the demands for more potent antigenspecific responses, specific types of immune responses, and a high margin of safety. Nanotechnology provides a multifunctional stage for the integration of desired adjuvant activities performed by the building blocks of tailor-designed nanoparticles. Using nanomaterials for antigen delivery can provide high bioavailability, sustained and controlled release profiles, and targeting and imaging properties resulting from manipulation of the nanomaterials' physicochemical properties. Moreover, the inherent immune-regulating activity of particular nanomaterials can further promote and shape the cellular and humoral immune responses toward desired types. The combination of both the delivery function and immunomodulatory effect of nanomaterials as adjuvants is thought to largely benefit the immune outcomes of vaccination. In this review, we will address the current achievements of nanotechnology in the development of novel adjuvants. The potential mechanisms by which nanomaterials impact the immune responses to a vaccine and how physicochemical properties, including size, surface charge and surface modification, impact their resulting immunological outcomes will be discussed. This review aims to provide concentrated information to promote new insights for the development of novel vaccine adjuvants.

Advancements in prophylactic and therapeutic nanovaccines

“…Nanoparticles have also shown potential to be used as adjuvants because of their immunomodulating activities such as inflammasome activation, complement system activation and recruitment of immune cells [50] . Due to above-mentioned effects, nanoparticles act as a better adjuvant in comparison to complete Freund's adjuvant and conventional aluminum containing salts by inducing higher immunogenic responses at low antigen doses [51] .…”

“…Despite constant efforts to develop effective cancer vaccines, their efficacy in clinics has always been limited. Nonetheless, two prophylactic vaccines for hepatitis B virus-associated liver cancer and human papillomavirus virus-associated cervical cancer have been approved by US FDA till now [50] . The prophylactic vaccine development for cancer eradication is a challenge due to inefficient identification of tumor-specific antigens (neoantigens), rapid clearance with less accumulation in the lymphoid organs and generation of weak memory immune response.…”

Nanomaterials for cancer immunotherapy

“…Certain nanomaterials may have inherent immune-regulatory activities in cellular and humoral immune responses, in that these nanomaterials can help to promote antigen presentation or stimulate immune responses without the incorporation of specific adjuvants [68, 69]. For example, cationic lipid (R)-DOTAP is an immunologically active enantiomer of the DOTAP racemic mixture, and could initiate a strong immune response in an exogenous antigen model [70, 71].…”

Aminated nanomicelles as a designer vaccine adjuvant to trigger inflammasomes and multiple arms of the innate immune response in lymph nodes

“…Clusters within the marrow suspension were disintegrated by vigorous pipetting. After one wash (490× g, 5 minutes) in RPMI 1640 medium, the red blood cells were depleted with 0.83 M NH 4 Cl buffer (Sigma-Aldrich). Bone marrow cells (2×10 6 cells) were collected and cultured in 100-mm Petri dishes containing 10 mL of RPMI 1640 medium supplemented with 10% heat-inactivated fetal bovine serum, 50 IU mL −1 penicillin, 50 mg mL −1 streptomycin, and 20 ng mL −1 mouse recombinant granulocyte macrophage colony-stimulating factor (R&D Systems, Minneapolis, MN, USA).…”

“…[1][2][3][4][5][6][7] Lymphatic vessels have evolved to drain pathogens into lymph nodes, which provide a first line of defense against invading viruses and the initiation/ subsequent direction of adaptive immune responses for the removal of pathogens. [8][9][10] Nodal antigen-presenting cells (APCs) detect danger signals through pattern recognition receptors and initiate multiple arms of innate immune response such as the activation of inflammasomes and the secretion of proinflammatory cytokines and type I interferons (IFNs).…”