Researchers from the United States and Germany demonstrated the preclynic efficacy of a new candidate vaccine that opposes severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the agent causing coronavirus disease 2019 (COVID-19).
The Pfizer and BioNTech vaccine, called BNT162b2, has already been tested in Phase 1 clinical trials and has now progressed to a 2/3 global efficacy and protection trial.
Ugur Sahin (University Medical Center, Johannes Gutenberg University, Mainz, Germany) and his colleagues say his preclinical study has now shown that the vaccine is highly immunogenic in rhesus mice and macaques.
In mice, a single injection of BNT162b2 induced maximum levels of neutralizing antibodies opposed to SARS-CoV-2 and responses to hard interferons (IFNs) and T cells that the authors believe may oppose infectious provocation.
In rhesus macaques, the premium booster vaccine with BNT162b2 induced neutralizing antibody titers up to 18 times higher than those generated when convalescent human serum was used.
The new vaccine also candidates the lungs of rhesus macaques of infectious challenge through SARS-CoV-2.
You must have a preprinted edition of the article on the bioRxiv server, while the article is peer-reviewed.
Since the first cases of coronavirus disease 2019 (COVID-19) were first known in Wuhan, China, due last year, researchers have rushed to expand effective vaccines that will help protect against SARS-CoV-2 infection.
To infect host cells, SARS-CoV-2 uses a spike viral surface protein to bind to human angiotensin converting enzyme (ACE2) receptor 2.
The Spike protein binds to ACE2, a receptor-binding domain (RBD) that is a component of its N-terminal furin cleavage fragment (S1). The Spike protein then uses a fusion mechanism contained in the C-terminal furin cleavage fragment (S2) to fuse with the mobile membrane and deliver the viral genome to the mobile host.
Sahin and his colleagues say that this membrane fusion can be blocked by mutating The Spike residues 986 and 987 into prolines to form a Spike antigen that is stabilized in the prefusion (P2 S) formation.
RBD is the number one target for neutralizing antibodies after infection with SARS-CoV-2 and has a “rising conformation” in which many neutralizing epitopes are exposed and a “descending” formation in which not many epitopes are exposed. .
The team described the progression of BNT162b2, which is a modified mRN nucleoside that encodes P2 S with a local furin excision site, resulting in S1 and S2 excision fragments.
The nucleoside amendment dampens innate immune detection and in vivo RNA translation. Previous studies have already shown that modified RNA vaccines are immunogenic unlike several viruses.
Now, Sahin and her colleagues have that BNT162b2, which encodes the captured Spike protein in a pre-fusion conformation, is highly immunogenic in mice and rhesus macaques.
After expressing the BNT162b2 coding series in cells, approximately one-fifth of Spike’s un-RBD proteins “up”, two-RBD “down”.
“This research showed that antigenically vital RBD can simply take the ‘ascending’ conformation, with the receptor binding site in the neutralizing epitopes available in a proportion of molecules,” the team wrote.
In mice, a single dose of BNT162b2 elicited higher neutralizing antibody titers and harsh responses of CD4 helper cells type T (TH1) and follicular helper T cells (TFH). It has also produced strong responses of THE IFN T, interleukin 2 (IL – 2) and CD8 cells.
“Both types of CD4 T cells induced through BNT162b2 can generate and mature express antigenic antibodies and potentially oppose infectious provocation,” the team wrote.
Premium booster vaccination in rhesus macaques generated neutralizing antibody names that were 10. 2 to 18. 0 times higher than those seen when a human serum convalescent SARS-CoV-2 panel was used. marker five weeks later.
In addition, the vaccine absolutely the lungs of rhesus macaques (2 to 4 years old) oppose infection, after exposure to SARS-CoV-2. Quantitative opposite transcriptase polymerase chain reaction (RT-qPCR) assays did not discover detectable SARS-CoV-2 RNA in serial bronchoalveolar wash samples taken from animals 3 days after exposure.
The authors argue that the harsh reaction of TH1-biased CD4 T cells and the reaction of CD8-T-T cells to BNT162b2 are desirable for vaccine protection and efficacy and delivery assurance studies for clinical translation.
“A global phase 2/3 immunization effectiveness and protection test with BNT162b2 (NCT04368728) is underway,” says the team.
bioRxiv publishes initial clinical reports that are not peer reviewed and should therefore not be considered conclusive, the consultant’s clinical practice/health-related behaviors, nor treated as established information.
Written by
Sally holds a bachelor’s degree in biomedical sciences (B. Sc. ). He specializes in reviewing and synthesizing the latest discoveries in all covered medical spaces in major world-renowned, high-impact foreign medical journals, foreign press conferences, and newsletters from government agencies and regulators. At News-Medical, Sally generates news, articles about life sciences, and interview coverage.
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