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Can the deployment of COVID-19 vaccination prevent future outbreaks of coronavirus?




A new study found that the development of a vaccine against the 2019 coronavirus disease (COVID-19) pandemic not only prevented infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but also in other endemic diseases. It suggests that there is a possibility of a pandemic. Coronavirus The same is true for (CoV).

The preprinted version of the survey is Bio Rxiv* While the server, article is being peer reviewed.

SARS-CoV-2 vaccine induces cross-reactive CoV antibody in humans

The use of the SARS-CoV-2 vaccine in humans was, of course, associated with a marked increase in antibodies against this virus, but of cross-reactive antibodies against SARS-CoV-1 and the common cold coronavirus OC43. It was also associated with the increase. History of infection with SARS-CoV-2.

COVID-19 patients have also developed antibodies that recognize all three viruses.

Mouse research

Studies in mice have shown that vaccination against SARS-CoV-2 protected animals from SARS-CoV-2 and SARS-CoV-1. Various vaccine platforms have been tested with the same results, including adenovirus vector-based, mRNA-based, inactivated virus-based, spike-based, or receptor-binding domain (RBD) -based only.

Experimental SARS-CoV-1 spike vaccines have previously been shown to protect mice from SARS-CoV-1 infection.The sera of these immune mice showed cross-reactive partial inhibition of SARS-CoV-2. Fake virus Invasion of cells in cell culture.

Mice vaccinated with the SARS-CoV-1 vector vaccine were 280 times better protected when subsequently challenged with SARS-CoV-2.

Cross-reactive antibody response after SARS-CoV-2 vaccination in mice.  (A) Antibody response after Ad5-SARS-CoV-2 spike vaccination.  (B) Antibody response after VSV-SARS-CoV-2 spike vaccination.  (C) Antibody response after mRNA-SARS-CoV-2 spike vaccination.  (D) Antigen-antibody reaction after SARS-CoV-2 RBD vaccination.  (E) SARS-CoV-2

Cross-reactive antibody response after SARS-CoV-2 vaccination in mice. (A) Antibody response after Ad5-SARS-CoV-2 spike vaccination. (B) Antibody response after VSV-SARS-CoV-2 spike vaccination. (C) Antibody response after mRNA-SARS-CoV-2 spike vaccination. (D) Antigen-antibody reaction after SARS-CoV-2 RBD vaccination. (E) SARS-CoV-2 “whole” antibody response after vaccination. (F) Antibody response after inactivated SARS-CoV-2 vaccination. Mice were intramuscularly primed and boost immunized after 3 weeks (see Materials and Methods for vaccination information). Antibody response was assessed by ELISA 2 weeks after boost. Experiments were performed using wild-type C57BL / 6 mice, with the exception of VSV-SARSCoV-2 spike vaccination using k18-hACE2 (C57BL / 6) mice. Each panel provides examples of clinically approved SARS-CoV-2 vaccines based on the same vaccine modality in parentheses. The dashed line represents the detection limit. The data are from one representative experiment in the n = 5 / group. The experiment was performed 2-3 times and similar results were obtained. *, P <0.05, **, P <0.01、ns、P > 0.05, Mann Whitney U test.

Gene identification mediates cross-reactivity

In mice, the SARS-CoV-1 vaccine induced SARS-CoV-2 specific CD8 + T cells. Protein subunits and inactivated viral vaccines do not elicit this response, unlike other vaccine platforms, because they do not produce viral proteins in the host cell.

Cross-reactive responses are mediated by the identity of viral genes between different viruses. Since the SARS-CoV-1 and SARS-CoV-2 peaplomers share 76% of the antigen identity, vaccination of the former induces a strong protective antibody against the latter.

This study identified two highly conserved antibody binding sites on peplomers that may be involved in this cross-reactive T cell response.

Conversely, 37% identity between SARS-CoV-2 spikes and OC43 spikes means that SARS-CoV-2 spike-based vaccination failed to protect against the latter virus. However, the use of the nucleocapsid-based SARS-CoV-2 vaccine provided partial protection, despite only 38% identity.

Again, spike-based vaccines were more effective in inducing cross-reactive antibodies than RBD-based vaccines. Probably because the former has a large number of conserved epitopes and induces a wide range of CoV responses.

Cross-reactivity after infection

Infection with CoV elicited antibodies that also protected against subsequent infection with other CoVs. In particular, mouse infections with epidemic human CoVs were associated with increased protection against other mouse CoVs (320-fold). Conversely, infecting mice with one mouse CoV caused sterilization immunity against other mouse CoVs.

T cells important for cross-reactive immunity

Both T-cell-mediated immunity and humoral immunity were associated with this cross-defense response to vaccination. Using a dendritic cell (DC) -based vaccine designed to evade antibody reactions, including antigenic peptides from SARS-CoV-2 spikes, envelopes, membranes, and nucleocapsid proteins, researchers have found CD8 + T. Obtained cells.

Surprisingly, this vaccine was protected from attack by mouse CoV. Immune sera induced by the SARS-CoV-1 spike vaccine protected untreated mice from mouse CoV infection, despite the fact that both spike antigens were only 30% identical.

What is the impact?

The researcher wrote:

These data show that coronavirus infection can provide partial or complete protection against future infections by other coronaviruses. We also observed patterns in which the degree of heterologous protection appeared to be proportional to the genetic similarity between the first coronavirus and subsequent coronavirus infections.

An important implication of these findings is that different SARS-CoV-2 variants have 99% identical spike antigens, so antibodies induced by one of the variants are protective against infection by another strain. Is likely to be.

Another observation is Efficacy of Infection in the induction of cross-reactive antibodies compared to vaccination. The reason is that viral infections induce antibodies against many antigens, most of which are conserved between CoVs. Most coronavirus vaccines, on the other hand, use the least conserved spike antigen of the CoV protein.

This may suggest that additional viral antigens need to be added when designing next-generation vaccines in order to broaden CoV coverage and provide pancorona virus vaccines.

The duration of immunity remains questionable. It depends in part on whether these broad defense antibodies are produced at the plasma cell level or by plasma cells. The former is a short-lived cell type that produces highly specific cross-reactive antibodies during the acute phase of infection, whereas plasma cells produce a permanent response.

The SARS-CoV-2 nucleocapsid protein is composed of several sequences, some of which are highly conserved. In fact, for human CoVs such as OC43, bat CoVs, and mouse CoVs, one is pretty much the same.

Such long-conserved sequences are generally associated with inducing cross-reactive T cells to CoV. If so, nucleocapsids may be the best tool for universal CoV vaccines.

This study is “First definitive proof of heterologous immune defense after coronavirus vaccination or infectionBy demonstrating that previous CoV infections and CoV-based vaccines induce cross-reactivity protection against other CoVs, researchers suggest an approach to vaccine design that covers a wider range of pathogens.

*Important Notices

Bio Rxiv Is not considered definitive, guides clinical practice / health-related behaviors, or is treated as established information because it publishes preliminary scientific reports that have not been peer-reviewed. Please.


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