The new “multi-tope” vaccine is promising in the fight against COVID-19

Researchers in the United States and Taiwan reveal the potential of a new protein peptide vaccine to prevent infection with drugs that cause severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – coronavirus disease 2019 (COVID-19) Demonstrated.

Image credit: https://www.biorxiv.org/content/10.1101/2020.11.30.399154v1.full.pdf

Chang Yi Wang and colleagues at United Biomedical Inc Asia in Taipei state that a vaccine called UB-612 is the first “multi-tope” protein peptide vaccine developed for SARS-CoV-2.

The UB-612 consists of several components designed to provide a high level of guidance. Neutralizing antibody A wide range of immune cell responses, including viral fusion proteins, and five synthetic SARS-CoV-2 derived peptides.

Studies in guinea pigs, rats, mice and rhesus monkeys confirm immunogenicity Effectiveness of Toxicity studies of UB-612 in rats have shown that the vaccine is safe and well tolerated.

UB-612 is responsible for the prevention of SARS-CoV-2 infection and COVID-19 disease, as UB-612’s First in Human (FIH) clinical trial has begun in Taiwan and future trials are planned worldwide. A very promising vaccine candidate for. King and team.

A preprinted version of the treatise is available on the server bioRxiv *, but the article has been peer reviewed.

Researchers compete to develop vaccines

Since the outbreak of COVID-19 began in Wuhan, China at the end of last year (2019), this unprecedented global public health crisis has led researchers around the world to design vaccines against SARS-CoV-2. Encourages urgent efforts by.

Hundreds of candidate vaccines have been developed, some of which have already reached the late stages of clinical trials.

SARS-CoV-2 has a large viral RNA genome approximately 30 kb long that encodes 29 proteins. Four of these proteins are structural spike (S), membrane (M), envelope (E), and nucleocapsid (N) proteins.

The main structural proteins used by SARS-CoV-2 to infect cells are spike (S), class I fusion. Glycoprotein It is divided into two functionally different subunits.

Subunit 1 (S1) contains a receptor binding domain (RBD) that is directly involved in the human host cell receptor angiotensin converting enzyme 2 (ACE2). Therefore, S1 determines the degree of viral tissue tropism (specific targeting of specific host tissues) and pathogenicity.

Subunit 2 (S2) has a fusion peptide that drives the virus and hosts membrane fusion to allow delivery of viral RNA to the host cell.

Most vaccines currently being evaluated in clinical trials target only the full-length S protein with the goal of inducing a neutralizing antibody response.

Targeting only spikes can cause problems

“Neutralization of S protein alone is unlikely to provide lasting protection against SARS-CoV-2 and its new mutants with mutated B cell epitopes,” Wang et al. Write. “Induction of T cell response is limited compared to the response produced by natural multigenic SARS-CoV-2 infection.”

S1-RBD is an important component of SARS-CoV-2. This domain is required for host cell adhesion and is a major immunogen for the induction of neutralizing antibodies and memory B cell responses.

A long-term cellular response can enhance the initial neutralization response (through activation of memory B cells) and provide a much longer immune period as antibody titers decrease. “

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Due to the obvious advantages of the vaccine, which contains the potent S1-RBD vaccine component, the team developed three S1-RBD binding constructs and tested their immunogenicity in guinea pigs.

The most potent immunogen was S1-RBD-sFc

Of the three candidates, the most potent immunogen was S1-RBD-sFc. S1-RBD is fused to the single-strand fragment crystallization region (sFc) of human immunoglobulin 1.

This construct elicited the antibody with the strongest functional activity, as quantified by inhibition of viral binding to ACE2 and neutralization of live SARS-CoV-2.

“Based on these results, the S1-RBD-sFc protein was selected as the primary candidate for the B cell component of the vaccine,” the team said.

Literature searches were performed to provide immunogens that elicit T cell responses, and T helpers (Th) and cytotoxic T cells (CTL) derived from the S, N, and M proteins of SARS-CoV-2. The epitope was identified. Five peptides were selected and additional designs were made.

Next, tests of the primary candidate S1-RBD-sFc construct further formulated with Th and CTL peptides were performed in rats, mice, and rhesus monkeys to confirm the immunogenicity and efficacy of UB-612.

In addition, the results of a good laboratory practice (GLP) repeated dose toxicity study in rats showed that the UB-612 vaccine was safe and well tolerated.

“Very promising” vaccine candidates

“We challenge high doses of SARS-CoV-2 without inducing immunopathology in the lungs and have very high levels of neutralizing antibodies and Th1-prone immunity induced by vaccines that protect animals. We responded, “says Wang and the team.

Overall, the researchers say they have demonstrated a proof of concept for the first multitope protein, UB-612, and a peptide-based vaccine against SARS-CoV-2.

UB-612 is highly promising for the prevention of SARS-CoV-2 infection and COVID-19 disease, as Phase 1 trials are underway in Taiwan and additional trials are planned worldwide. It is a differentiated vaccine candidate. “

*Important Notices

bioRxiv Publish preliminary scientific reports that should not be considered definitive as they are not peer-reviewed, guide clinical practice / health-related behaviors, and should not be treated as established information.