SARS-CoV-2 DNA vaccine tested in an animal model

Vaccines against severe acute coronavirus syndrome 2 (SARS-CoV-2) are being distributed worldwide to control COVID-19 pandemic (coronavirus 2019 disease). Multiple vaccines are needed to treat the various diseases and overcome the potential challenges of conventional vaccines (such as high cost, or low immunity).

In this context, a team of experts has tested the immune responses obtained by mucosal homologous plasmid and heterologous immunization strategy using plasmid vaccine and Modified Vaccinia Ankara (MVA) spike (S) SARS-CoV-2 and nucleocapsid (N) antigens. The research is published in the journal Vaccines.

The scientists describe the preclinical development of a heterologous, 2-dose heterologous vaccine candidate against COVID-19 using the QAC diagnostic system (quil-A chitosan). They showed that the pQAC / MVA-CoV-vaccinated mice effectively neutralized the wild-type SARS-CoV-2.

They found that only the heterologous intranasal vaccination strategy involved the neutralization of antibodies against SARS-CoV-2 in serum and bronchoalveolar lavage of mice. This finding indicates that this is a protective vaccine. They reported that this strategy induced induction of type 1 and type 17 T-cell responses and polyfunctional T cells expressing type 1 multiple cytokines (e.g., IFN-γ, TNFα, IL- 2) in the lungs and spleens the vaccine. mice.

The researchers found that the plasmid homologous immunization strategy resulted in the induction of local and multifactorial mono T cells producing IFN-γ.

The researchers noted that several vaccine boosters could be used together to effectively vaccinate patients.

In the study, the researchers have used 1) vectored (DNA and viral) vaccines – because plasmids encoding antigens can be developed within a few days with fast and cheap gene synthesis technologies, and 2) viral viral vaccines such as the Vaccinia Ankara Modified (MVA Material) – highly efficient scale-up production processes have already been established.

Although the DNA vaccines are temperature stable (without the need for cold chain logging), these DNA structures are contaminated in vivo and DNases. This leads to ineffective uptake by antigen-expressing cells (APC) and thus causes low immunogenicity.

To overcome this challenge in the use of DNA vaccination, the researchers have used an articulate delivery system such as the full-fledged chitosan-A (QAC). Chitosan is a bioavailable natural polysaccharide that is complex with the DNA due to its high cost. The A-quilt is a strong enhancer with smooth surface properties. The QAC diagnostic system expands if the active plasmid secretes antigens.

In a previous study, the researchers showed that a 2-dose QAC containing DNA plasmid (pQAC) encoding the nucleocapsid (N) gene against a bird’s coronavirus received strong T- responses. cell without contributing to humoral responses.

With this observation, the researchers proceeded to develop a heterologous strategy with encapsulated QAC plasmid core DNA (pQAC), followed by an increase in MVA, in anticipation of a broader immune response. Both pQAC plasmids (pQAC-CoV) and vector MVA (MVA-CoV) were designed to express the SARS-CoV-2-encoded S (spike) and N (nucleocapsid) antigens from early COVID-19 pandemic.

The researchers maintained that the pQAC / MVA-CoV induced both systemic and local neutral antibodies in mice (when vaccinated intravenously), with cellular responses Th17 local. In addition, they reported that mice vaccinated with direct plasmid vectors (pQAC-CoV) generated good cellular 1 and type 17 responses (Tc17 or Th17). They considered local and systemic defense response in detail in the paper.

Based on the reported studies on the levels of anti-SARS antibodies, B memory cells and T cells, the researchers have noticed that the directly responsible vaccines may not produce a neutral antibody response ( which decreases within 3 months after delivery) long-term protection against SARS-CoV-2 and other coronaviruses.

With this in mind, the researchers have studied vaccines against SARS-CoV-2 – which may stimulate a low and cellular immune response. Clearly, this could provide a sustained immune response of the vaccines that were just focused on neutralizing antibodies.

“Currently, most experimental DNA vaccines are only available for intramuscular administration limiting mucosal immunity necessary to reduce viral infection.”

With new infectious diseases, new vaccines are always needed. Vaccines engineered by well-matured processes enable their convenience during a pandemic such as COVID-19. Custom vaccine uptake offers highly flexible vaccination programs. Because the heterologous vaccine elicited local and systemic humoral and T-cell immune responses, the researchers have reported that the heterologous vaccination strategy may be superior to sterilizing immunity against SARS-CoV -2.