V8 COVID-19 Vaccine Development and a Potential Nanomaterial Path Forward

Nanotechnology might benefit modern vaccine design since nanomaterials are usable for antigen delivery, as adjuvants, and as mimics of viral structures.

The rapid development of vaccines is possible because the genome and structural information of SARS-CoV-2 was made available in record time10,11,12,13,14.

When designing a vaccine, principally, one needs to define the antigen, the adjuvant, the manufacturing system and the delivery strategy.

Definitions

Components and options in vaccine design

Antigen: a foreign material that can induce an immune response within the body—often derived from the pathogen one aims to immunize against. Based on how the antigen is presented, vaccines can be categorized as:

  • Live-attenuated vaccine: weakened form of pathogens capable of replication, but not causing illness.

  • Inactivated vaccine: killed form of pathogens incapable of replication or infection.

  • Subunit vaccine: minimal antigenic element of a pathogen, for example, a protein, protein subunit or polysaccharides or VLPs self-assembled from these components. These antigens in purified forms are administered in combination with molecular adjuvants or expressed in vivo using RNA, DNA or viral vectors.

  • Peptide-based vaccines: peptides are fundamental element of a protein subunit recognized by the immune system; all antigens described above contain peptide epitopes.

Adjuvant: a stimulatory agent designed to boost immune response toward a co-delivered antigen.

  • Occurs as ‘independent entities’ in a mixture with antigens.

  • Occurs as ‘conjugate-entities’ via chemical fusion directly to antigens.

Nanoparticle/nanocarrier: The live-attenuated and inactivated viral vaccines can be regarded as nanoparticles themselves. Rather than serving as the vaccine itself, a nanoparticle (viral or non-viral) can be employed as nanocarrier to encapsulate or present the antigen payload or nucleic acid encoding the antigen. Nanocarriers provide stability and targeting of these payloads to antigen presenting cells (APCs); nanocarriers can confer innate adjuvant behavior (see Fig. 3). Nanocarriers synchronize delivery of both, antigen and adjuvant, to target immune cells.

  • Viral vector: repurposed mammalian viruses engineered to deliver a gene encoding the antigen (examples include adenoviral vectors derived from chimpanzee and human).

  • Proteinaceous nanoparticles: nanoscale biomaterial assemblies with atomic precision and complexity (examples include protein nanocages and non-infectious viruses such as plant viruses or bacteriophages) engineered to present a subunit vaccine or deliver a nucleic acid encoding the antigen.

  • Synthetic nanoparticles: nanoscale assemblies of synthetic materials (examples include polymer, liposomal, or lipid nanoparticles) engineered to present a subunit vaccine or deliver a nucleic acid encoding the antigen.

Device: a piece of equipment designed to administer vaccine (Fig. 4).

  • Syringe: hypodermic needle used for intramuscular, subcutaneous or intradermal delivery of vaccine by a healthcare professional (>10 mm length and 0.25–0.5 mm in outer diameter, somewhat invasive)

  • Implant: slow-release device containing vaccine for sustained subcutaneous delivery, administered by a healthcare professional (<10 mm in length and <2 mm in width, more invasive)

  • Microneedle patch: array of micro-metre-scale needles containing vaccine for slow release, sustained intradermal delivery, administered by a healthcare professional or via self-administration (<1 mm in length and 0.1–0.5 mm in width, approximately 1 cm2 patch, minimally invasive).

  • Live-attenuated vaccines (LAVs) are live, reproducing but avirulent viruses. LAV design intends single-dose immunity without illness. Frontrunner vaccine candidates. LAVs bear risks of transfer of the virus and/or reversion to the pathogenic form, reactivation in immune-compromised individuals or recombination with related viruses circulating in the population

  • Inactivated vaccines (IVs) are heat or chemically inactivated pathogens or fractions thereof. These vaccine formulations are incapable of replication and safer than LAVs, but their inactivation results in lowered immunogenicity and requirement for multiple-dose regimens to establish long-lasting immunity; these vaccine formulations often require adjuvants to immunize the aging population due to immune senescence37

  • Adenoviral Vectors have several vaccine candidates in development that utilize non-replicating adenoviral vectors. Leading adenoviral vectors in SARS-CoV-2 clinical trials are adenovirus type 5 vector (Ad5-nCoV) as of 16 March 2020 and chimpanzee adenovirus vaccine vector (ChAdOx1).

  • While DNA vaccines offer higher stability over mRNA vaccines, the mRNA is non-integrating and therefore poses no risk of insertional mutagenesis. Additionally, the half-life, stability and immunogenicity of mRNA can be tuned through established modifications45

  • Subunit vaccine candidates constitute minimal structural components of SARS-CoV-2 that can prime protective immune responses in the host when administered with molecular adjuvants for enhanced immunogenicity. 

  • VLP subunit vaccines can also take the form of protein nanoparticles or virus-like particles (VLPs). VLP vaccines can be produced by recombinant expression and allows for genetic engineering to incorporate ligands, immunomodulators and targeting moieties.

  • COVID-19 vaccine development and a potential nanomaterial path forward | Nature Nanotechnology

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