The rise of nanovaccine technology: strategies to improve immune response to nanovaccine: P2

The flexible design of nanomaterials confers better specific immune responses to nanovaccines, mainly due to the unique drug/antigen delivery properties of nanomedicines and nanomodulation of immunity.

Targeted delivery of antigens to critical cells and tissues

Drug delivery is one of the most promising nanotechnology applications. When it comes to vaccination, it's also crucial to get antigens to the right spot in the immune system. Antigen vaccine distribution involves spatiotemporal interactions of several cell types, including antigen presenting cells (APCs), B cells, different T cells, macrophages, and neutrophils, unlike other kinds of drug delivery by specialized cell types. In addition, the above interactions generally occur in specific tissues or regions, further complicating antigen delivery. As a result, various promising strategies for designing nanovaccines have been used, including crossing biological barriers, lymph node (LN) transport, controlled antigen release, APC targeting, and cross-presentation.

For example, 20-200 nm nanoparticles are more readily internalized by a common APC, dendritic cells (DCs). Targeted nanoparticle delivery to DCs can be achieved by modifying affinity-based targeting of specific ligands of DC subpopulations, such as C-type lectin receptors. In addition, multivalent antigen structures were found to enhance antigen recognition and activation of another APC, B cells.

Polyvalent effect of nanovaccines

There is evidence that multivalent effects can trigger stronger humoral and cellular immune responses in self-assembled peptide nanoparticles, multi-antigen-binding nanoparticles, and other multivalent combinations. Encouragingly, nanotechnology offers a definite advantage in manipulating antigen density and orientation, providing a good platform to study the potential mechanisms of multivalent effects and their optimization strategies.

For example, it was found that liposomes containing multivalent HIV trimers increased the intensity of the antibody response against the protein region of the target antigen. Further studies have shown that antibody responses can be formed by programming specific epitopes. Vaccine specificity can be increased by burying unwanted epitopes and exposing desired epitopes, thereby reducing the response to the immunodominant non-neutralizing region of the HIV trimer.

Carrying nucleic acids to express antigens in vivo

The successful application of the COVID-19 vaccine demonstrates the unlimited potential of mRNA vaccines. The efficacy of nucleic acid-based vaccines depends largely on the delivery of DNA or RNA that upregulates the expression of target-encoded antigens and triggers specific, strong immune responses in target immune cells.

DNA vaccines are simple, stable, and inexpensive to mass produce. However, inefficient in vivo delivery of plasmid DNA (pDNA) compromises its effectiveness and limits further preclinical applications. In contrast, mRNA vaccines offer more significant points with better antigen expression and faster clearance rates, where nanotechnology plays an important role. Cationic lipids are the most commonly used nanomaterials, which help protect mRNA from degradation and immune recognition.

In situ triggering of tumor antigen release

Immunoadjuvants and other immune stimulation strategies

Immune adjuvants are an integral component of vaccines and play a complementary role in enhancing the immune system's response to antigens. Some nanomaterials have intrinsic adjuvant properties that promote cytokine secretion and activate immune signaling pathways. In addition, nanomaterials with phototherapeutic or reactive oxygen species generation properties may also induce ICD effects in cancer immunotherapy. These self-adjuvant nanomaterials provide more possibilities and potential for nanomedicine applications in vaccines.

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