Controlling the spread of the human immunodeficiency (HIV) virus might be the only feasible route for completely avoiding an intractable disease. However, crucial immunities are still difficult to be sufficiently triggered by vaccines alone, which greatly limits its practical application.

Researchers from the Microfluidic-Biomaterials Lab at the Southern University of Science and Technology (SUSTech) have developed a two-dimensional nano-adjuvant comprising of rare-earth elements that improve the immunities generated by vaccines (HIV DNA vaccine in this case).

The research article, entitled “Two-dimensional nanosheets as immunoregulator improve HIV vaccine efficacy,” was published in Chemical Science, a scientific journal covering all aspects of chemistry.

Introducing applicable immunoregulatory building blocks in a material endowing with inherent immunoregulatory characteristics is a strenuous task. The rare-earth materials, because of an inherent immunoregulatory capability, regulate the behavior of macrophages (antigen representing cells) and immunity. Considering that multiple types of rare-earth elements have immunoregulatory effects on the functions or behaviors of immune effector cells, selecting rare-earth elements rationally is a core question for the design of immunoregulatory nanomaterials. 

Wisely chosen rare-earth elements, erbium (Er) and dysprosium (Dy), activate macrophages and improve phagocytosis capability and bioactivity for the increased presentation of antigens. The heterogeneity of 2D NSs comprehensively regulates immune functions of both Er (ROS-based mechanism) and Dy (NO-based mechanism), in comparison with either Er- or Dy-alone.

Because of the planar morphology, these 2D NSs target the mice lymph nodes without the use of any lymph node targeting functional molecules. Considering lymph node is a critical type of immunological tissue for mediating immune responses, the lymph node targeting capability of nanosheets effectively improve the efficacy of vaccines.

Figure 1. Characterization of rare-earth 2D NSs

In regulating DNA vaccine-triggered immune responses, the 2D NSs simultaneously improve both humoral and cellular immune responses, compared to most other reported immunoregulators, which can only enhance either humoral or cellular responses. 2D NSs significantly improve the HIV-specific humoral response of IgG and the four subclasses (IgG1, IgG2a, IgG2b, and IgG3).

Furthermore, the 2D NSs boost the enhancement of cytotoxic T lymphocytes to produce HIV-specific IFN-γ to neutralize HIV-infected cells. The balanced enhancement of HIV-specific humoral and cellular immune responses regulated by 2D NSs gives an unparalleled advantage for realizing the neutralization (mediated by humoral response) and cytotoxicity (cellular response) against HIV.

Figure 2. 2D NSs regulating HIV DNA vaccine-triggered immune responses

2D NSs-regulated HIV vaccine triggers six critical genes associated with various immunoregulation-related networks. The three natural killer cell lectin-like receptor subfamily genes Klrk1, Klrd1, and Klrc1, are triggered by nanosheets, which can effectively enhance the presentation of antigens. The 2D NSs induce the upregulation of the genes Ccr2 and Serpinb9 to regulate cytokine production. The 2D NSs are found to significantly up-regulate the expression of Msr1, a critical gene that activates the macrophages. The 2D NSs influences the immunoregulation-related network involving the activation of immune cells, antigen presentation, and the production of immune effectors to facilitate the HIV DNA vaccine to trigger stronger immune responses.

Figure 3. Transcriptome profiling of 2D NSs improving HIV DNA vaccine

In summary, the realization of the concept of 2D NSs immunoregulator dramatically broadens the scope for choices to optimize the vaccination of infectious diseases, tumor immunotherapy, and other immune-based preventive treatment and therapy.

The Microfluidic-Biomaterials Lab at SUSTech is the corresponding author of this paper.

This work was supported by the National Natural Science Foundation of China (NSFC), the National Key R&D Program of China, the Shenzhen Key Laboratory of Smart Healthcare Engineering, and the Leading Medical Talents Program of Health Commission of Yunnan Province, and

Paper link: https://pubs.rsc.org/en/content/articlelanding/2022/SC/D1SC04044H

To read all stories about SUSTech science, subscribe to the monthly SUSTech Newsletter.