Pfizer, promising BioNTech COVID-19 vaccine candidate in preclinical study

Researchers in the United States and Germany demonstrated the precland 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 protection and efficacy 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 superior titers of neutralizing antibodies opposed to SARS-CoV-2 and responses to strong interferons (IFNs) and T cells that the authors believe may be opposed to the infectious challenge.

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 candidate also to the lungs of rhesus macaques of infectious provocation through SARS-CoV-2.

You must have a pre-printed edition of the article on the bioRxiv server, while the article is peer reviewed.

Since the first cases of the 2019 coronavirus disease (COVID-19) were first known in Wuhan, China, late last year, researchers have been quick to expand effective vaccines that will help protect against infection. by SARS-CoV-2.

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 host’s mobile.

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 SARS-CoV-2 infection and has a “rising conformation” in which many neutralizing epitopes are exposed and a “descending” array 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 shown that modified RNA vaccines are immunogenic as opposed to a number of viruses.

Now, Sahin and his colleagues have to BNT162b2, which encodes the captured Spike protein into a prefusion conformation, is highly immunogenic in rhesus mice and macaques.

After expressing the series encoding BNT162b2 in cells, approximately one-fifth of Spike proteins in the one-RBD state “up”, two-RBD “down”.

“This research showed that antigenically vital RBD can simply assume ‘up’ conformation, with the receptor binding site in the neutralizing epitopes available in a proportion of the molecules,” the team wrote.

In mice, a single dose of BNT162-2 elicited higher neutralizing antibody titers and potent mobile T helper CD4 + T (TH1) and T helper follicular T (TFH) responses. It also produced strong mobile responses of IFNγ +, interleukin 2 (IL-2 +), and CD8 + T.

“Both types of CD4 T cells induced through BNT162b2 can generate and mature express antigenic antibodies and potentially oppose infectious provocation,” the team wrote.

Top 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. Furthermore, the name of the neutralizing antibody is still 3. 3 times higher than this 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 CD4 T cells with TH1 bias and the reaction of CD8-T-T cells to BNT162b2 are desirable for vaccine protection and efficacy studies and assurance of supply for clinical translation.

“A global phase 2/3 immunization protection and efficacy 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 medical spaces covered in high-impact foreign medical journals, foreign press meetings, and advertisements from government agencies and regulators. At News-Medical, Sally generates news, articles about life sciences, and interview coverage.

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