Researchers are developing a ‘next generation vaccine platform’ against SARS-CoV-2

The etiologic agent of coronavirus disease 2019 (COVID-19), the true acute coronavirus 2 (SARS-CoV-2) respiratory syndrome, spreads effectively from person to person. Since the virus was first discovered in December 2019 in Wuhan, China, new mutations – with mutations at the virus’s spike proteins – have emerged, resulting in increased motility. With targeted and effective antiviral treatment options not currently available, large vaccines are our best bet in fully reversing the COVID-19 pandemic.

As countries around the world participate in major COVID-19 vaccination plans, with the rapid roll-out of effective vaccines despite a number of infectious diseases, further research and development in the field is needed. .

Researchers in Singapore have designed a subunit vaccine based on the SARS-CoV-2 spike protein co-administered with adjuvant CpG (Oligodeoxyribonucleotides). The researchers included both antigen and adjuvant with their artificial cell membrane (ACM) polymersome technology. This inclusion strengthens the immunity of the shape. The team have recently reported their promising results bioRxiv * paper in advance.

They found that their design resulted in strong neutralization against SARS-CoV-2 in C57BL / 6 mice. This required two doses of the prepared vaccine and the effect lasted for at least 40 days. In addition, they also test the presence of CD4 + and CD8 + T memory cells that produce Th1 cytokines. The research team’s model demonstrates effective and stable humoral and cellular immunity against SARS-CoV-2.

The SARS-CoV-2 belongs to the genus Betacoronavirus within the family Coronaviridae. Each virion is a nucleocapsid protein containing the single-stranded genomic RNA, surrounded by a lipid bilayer.

Into this lipid bilayer, the spike (S), membrane and envelope proteins are incorporated. The spike is a protein trimer with receptor binding domain (RBD) consisting of two subunits: S1 and S2. RBD of the spike protein enables viral entry into the host cell by interacting with the angiotensin-converting enzyme receptor 2 (ACE2) expressed on host cells.

The host proteases modulate the spike protein at the S1 – S2 junction and stimulate important structural rearrangement involving hydrophobic fusion peptide, thus allowing subsequent viral membrane and host cell union. to viral entry.

Because the spike protein is immunogenic and the target of antibodies and T cells – specifically CD4 + T cells – it has emerged as the main target for subunit vaccines of various modalities.

The researchers studied the immunological effect of artificial cell membrane polymersomes (ACM) on the various SARS-CoV-2 spike proteins (spike protein ectodomans, S2-only domain, and trimeric spike proteins).

The researchers created the spike protein, by injecting T.ni cells to produce a spike conversion that expressed areas S1 and S2. It excluded hydrophobic transmembrane land, thus improving protein flexibility. They used commercial S2 chip and trimeric spike protein as controls. The S2 was a particularly negative control because it did not strongly neutralize epitopes, but the trimeric spike was used as a positive control.

The traditional methods of vaccine models – using inactivated virus or live attenuation – require a biosafety level (BSL) 3 facility to treat SARS-CoV-2. Conventional mRNA vaccines require very cold maintenance conditions to maintain their stability. The high cost of vaccination is also a solution. Although the development of subunit vaccines is greatly accelerated, some key vaccine candidates still have to overcome some limitations.

Nanotechnology comes to the rescue: to develop a safe, cost-effective and scalable vaccination platform. Such a simple pathway, to well-defined nanoscale vesicles, is accomplished by the self-assembly of an amphiphilic block copolymer. Here, one can adjust the density of an internal block, body thickness and properties (including size and surface area).

In this study, the researchers use the artificial cell membrane (ACM) – self-accumulating nanoscale vesicles. These are polymersomes, structurally made of an amphiphilic block copolymer consisting of polybutadiene-b-polyethylene glycol (PBD-PEO) and cationic lipid 1,2- dioleoyl-3-trimethylammonium-propane (DOTAP ). These are delivery vehicles that are efficiently absorbed by dendritic cells, DC1 and DC2. Acceptance of dendritic cells, the most effective antigen-expressing cells (APC), is critical in initiating the altered immune response.

The researchers previously established that protein immunogenicity could be significantly improved through circulating within ACM polymersomes. The CpG used here is Murine CpG 1826.

Here, the researchers developed a subunit vaccine based on the SARS-CoV-2 spike protein, co-administered with adjuvant CpG. They have demonstrated the flexibility of the technology by incorporating different classes of biomolecules (DNA and proteins) within their proprietary ACM polymersomes to produce sensible and immunogenic granules.

The researchers are currently conducting further titration tests needed to determine the optimal dose for a high-quality antigen. Based on the observations of this study, they propose this study on the use of ACM technology to address the availability of antigen in pandemic.

* Important message

bioRxiv publish preliminary scientific reports that are not peer-reviewed and, therefore, should not be seen as final, guiding health-related clinical practice / behavior, or be treated as information established.