SARS-CoV-2 DNA vaccine tested in animal models

Vaccines against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) are being deployed worldwide to control the pandemic of COVID-19 (Coronavirus Disease 2019). Multiple vaccines are needed to deal with atypical epidemics and overcome the challenges posed by current vaccines, such as high cost and low immunogenicity.

In this regard, a team of experts used a plasmid vaccine and a modified vaccinia ancara (MVA) expressing SARS-CoV-2 spikes (S) and nucleocapsid (N) with a mucosal homologous plasmid-induced immune response. Tested the heterologous immune strategy. antigen..The study is published in the journal vaccine..

Scientists describe the preclinical development of a mucosal two-dose heterologous vaccine candidate for COVID-19 using the QAC (quil-A chitosan) adjuvant system. They showed that pQAC / MVA-CoV-immunized mice efficiently neutralize wild-type SARS-CoV-2.

They found that only heterogeneous intranasal immune strategies were elicited. Neutralizing antibody Against SARS-CoV-2 in mouse serum and bronchoalveolar lavage fluid. This finding suggests that this is a preventative vaccine. They found that this strategy allows multifunctional T cells that express type 1 and 17 T cell responses and multiple type 1 cytokines (eg, IFN-γ, TNFα, IL-2) in vaccinated lungs and spleen. Reported that it brought about the induction of. mouse.

Researchers have found that a plasmid homologous vaccine strategy leads to the induction of local monofunctional and multifunctional T cells that secrete IFN-γ.

Researchers have stated that multiple vaccine constructs can be used together to effectively immunize patients.

In this study, researchers used 1) vector (DNA and viral) vaccines-because plasmids encoding antigens can be developed within days with current rapid and inexpensive gene synthesis techniques, 2) modified vaccinia ancara. (Modified Vaccinia Ankara) Viral Vector Vaccine MVA) Strains-A highly efficient scale-up production process has already been set up.

Generation of humoral immune response in C57BL / 6 mice after immunization with different vaccine constructs. (A) Summary of vaccine constructs and immune protocols using a group of C57BL / 6 mice vaccinated with 3 doses of pQAC-CoV (IN) or pQAC-CoV (IM) at 3-week intervals. Another group of C57BL / 5 mice was vaccinated with pQAC-CoV (IN) at week 0, followed by boost immunization with MVA-CoV (IN) at week 6. (B) ELISA titer of SARS-CoV-2 S-specific IgG in mouse serum, (c) ELISA titer of SARS-CoV-2 spike receptor binding domain (RBD) -specific IgG in mouse serum and ( d) The significance of SARS-CoV-2 S-specific IgA (*, p <0.05, ****, p <0.0001) in ELISA titer bronchoplasmic lavage (BAL) was determined by bidirectional ANOVA. It was. The data shows the average SEM.

DNA vaccines are temperature stable (without the need for cold chain logistics), but these DNA constructs are degraded. In vivo According to DNase. This results in inefficient uptake by antigen-presenting cells (APCs) and reduced immunogenicity.

To overcome this challenge when using DNA vaccines, researchers have used articulated delivery systems such as quil-A-loaded chitosan (QAC). Chitosan is a biodegradable natural polysaccharide that forms a complex with DNA due to its positive charge. quil-A is a powerful adjuvant with mild surfactant properties. The QAC Particulate Adjuvant System prolongs the release of active plasmids that express the antigen.

In a previous study, researchers found that a double-dose QAC-encapsulated plasmid DNA (pQAC) encoding the nucleocapsid (N) gene against avian coronavirus produced a strong T-cell response without complementing the humoral response. Showed to trigger.

With this observation, researchers developed a heterologous strategy using QAC-encapsulated plasmid DNA (pQAC) prime followed by MVA boost, hoping for a broader immune response. Both the pQAC plasmid (pQAC-CoV) and the MVA vector (MVA-CoV) are designed to express the S (spike) and N (nucleocapsid) antigens encoded by SARS-CoV-2 from the early stages of COVID-19. It was designed. Pandemic.

Researchers have observed that pQAC / MVA-CoV induces both systemic and locally neutralizing antibodies in mice (when immunized intranasally) and is complemented by a localized Th17 cell response. .. In addition, they reported that mice vaccinated with the plasmid vector (pQAC-CoV) alone produced significant type 1 and type 17 (Tc17 or Th17) cellular responses. They discussed in detail the local and systemic immune responses in this paper.

Based on reported studies on levels of anti-SARS antibodies, memory B cells, and T cells, researchers have long given vaccines that rely solely on neutralizing antibody responses (decreased within 3 months of recovery). It points out that it may not be possible. -Long-term protection against SARS-CoV-2 and others Coronavirus..

With this in mind, researchers have researched vaccines against SARS-CoV-2 that can elicit both humoral and cell-mediated immune responses. Obviously, this may provide a more durable protective immune response than vaccines focused on neutralizing antibodies.

“Currently, most DNA vaccines are only suitable for intramuscular administration, which limits the mucosal immunity that is critically needed to reduce viral infection.”

New infections always require new vaccines. Vaccines designed with a well-standardized process enable their usefulness during pandemics such as COVID-19. The customizable vaccine construct provides a highly flexible vaccination program. Heterologous vaccination elicited both local and systemic humoral and T-cell immune responses, so researchers may be better off with heterologous vaccine strategies to provide bactericidal immunity to SARS-CoV-2. I assumed that there was sex.