SARS-CoV-2 / COVID-19

Since the end of 2019, a novel virus that can cause respiratory diseases and pneumonia has been spreading worldwide. The pathogen SARS-CoV-2 belongs to the coronavirus family and is closely related to the SARS virus, which caused a pandemic in 2002. Here we will keep you informed about current developments in research and provide answers to the most important questions.

With a vaccination, the immune system is trained to recognise pathogens and render them harmless. For this purpose, the pathogen is weakened, inactivated or only individual components of the pathogen are used. In this way, the immune system generates antibodies and T-cells that neutralise the pathogen, kill infected cells and forms an immune memory. In the event of renewed contact with the pathogen, the body can quickly recall the immune memory and fight off the infection.

For effective protection, vaccines should target multiple cell types in the immune system: Antibody-producing B cells and cytotoxic T cells that kill infected cells. Prof. Carlos A. Guzmán, head of the department "Vaccinology and Applied Microbiology" at HZI, highlights another aspect:

For an effective vaccination, you have to stimulate T-helper cells in parallel. This is the only way to get effective antibodies, and to form an immunological memory that induces the production of these very antibodies in the event of an infection.

HEAD OF THE DEPARTMENT OF VACCINOLOGY AND APPLIED MICROBIOLOGY

Most vaccines provide a booster shot at intervals of a few weeks for the best possible protection. This booster strengthens and improves the immune response.

Which vaccines against SARS-CoV-2 are authorised in Europe?

The structures of the pathogen that the immune system recognises are called antigens. From research on the SARS and MERS coronaviruses, it is known that antibodies that neutralise the spike protein on the surface of the virus prevent infection. Coronaviruses use the spike protein to bind to a receptor on the surface of the host cell and enter the cell.

Most vaccines against SARS-CoV-2 rely on the spike protein as a vaccine antigen. They differ in the way the spike protein enters the body.

mRNA vaccines

The first two vaccines against SARS-CoV-2 to be granted conditional marketing authorisation by the European Medicines Agency (EMA) are the mRNA vaccines from BioNTech & Pfizer and Moderna. Unlike traditional vaccines, this technology does not directly administer the vaccine antigen. Instead, the vaccine contains the blueprint in the form of single-stranded RNA packaged in lipid nanoparticles. The blueprint in the corona vaccines encodes the spike protein on the surface of the virus.

This messenger RNA (mRNA) is translated into proteins in the cytoplasm. Some of the spike proteins produced in cells are shown on the cell surface by antigen-presenting cells and recognised as foreign by other immune cells. This triggers an immune response that produces antibodies and cytotoxic T cells specifically directed against the coronavirus.

The vaccine mRNA, lipid nanoparticles and spike proteins are degraded by the body within a short time. However, the antibodies and spike-reactive immune cells are active for at least several months. Data over a longer period of time are not yet available.

The RNA vaccine has barely a chance of changing our genome. In extremely few cell types and situations (e.g. germ cells), there are genetic elements that encode the enzyme reverse transcriptase.

PROF CARLOS A. GUZMÁN, HEAD OF THE DEPARTMENT OF VACCINOLOGY AND APPLIED MICROBIOLOGY

Prof. Carlos A. Guzmán dispels concerns about the safety of mRNA vaccines in terms of promoting modifications of the human genome: "The RNA vaccine has barely a chance of changing our genome. In extremely few cell types and situations (e.g. germ cells), there are genetic elements that encode the enzyme reverse transcriptase. This enzyme is able to transcribe mRNA into cDNA, so while it is theoretically possible for an mRNA produced by the same cell (and there are hundreds of thousands of these) or mRNA introduced from outside to be transcribed into cDNA, this system works with incredibly poor efficiency. However, in the cells into which the mRNA enters through vaccination, these processes usually do not take place. It is also a fact that the mechanisms addressed already take place in the absence of the vaccine and an mRNA vaccine cannot influence such mechanisms."

The Helmholtz Association's "Klar soweit?" comic also explains how RNA vaccinations work (only in German).

Vector vaccines

Vector vaccines also do not contain the spike vaccine antigen as a protein, but only the blueprint for the protein. Unlike mRNA vaccines, a different, attenuated and harmless virus is used here as a transport system for transferring the genetic information for the spike protein.

In the EU, the vector vaccine of the University of Oxford and Astra-Zeneca has been approved since the end of January. These manufacturers use the attenuated chimpanzee adenovirus ChAdOx1. Viruses from the adenovirus family usually cause cold or flu-like symptoms. The genetic material of the adenovirus is manipulated in such a way that the virus can no longer reproduce.

ChAdOx1 binds to a receptor on the cell surface and thus enters the cell. The viral DNA is read in the cell nucleus and copied as mRNA. This is translated into the spike protein outside the cell nucleus. The process of the immune reaction to the spike protein is now comparable to that of the mRNA vaccines.

The vaccine Ad26.COV2.S from Johnson & Johnson, which was approved by the EMA in March, is also based on this mode of action. However, the vector virus used is an attenuated human adenovirus (adenovirus 26). In contrast to the vaccines approved until then, Ad26.COV2.S requires only one vaccine dose and no booster.

Vector vaccines and mRNA vaccines share the basic principle of eliciting a defence response without administering a pathogen or even a part of it. Rather, they get the body to produce the crucial antigen itself. Thanks to the "programmability" of the genetic information in the vaccines, they can be adapted relatively quickly when the virus changes.

The mode of action of these and other vaccines is explained by The New York Times in this series of articles: https://www.nytimes.com/interactive/2021/health/how-covid-19-vaccines-work.html

Vaccine research at HZI

Prof. Carlos A. Guzmán's department is researching a vaccine against SARS-CoV-2 that can be administered via the mucous membranes, thereby conferring superior protection against virus infection and transmission. Instead of being injected into the upper arm, the vaccine could be administered by nasal spray. An adjuvant developed at the HZI is used in this project. The adjuvant c-di-AMP enhances the immune system's reaction to the vaccine.

SUPPORT

With your donation to the HZI you directly support innovative coronavirus research projects that contribute to solutions for the containment of the virus and the identification of possible therapies. [more]

As with the already approved vaccines against SARS-CoV-2, the spike protein on the viral envelope serves as an antigen against which an immune response is generated. The researchers are focusing on a vaccine that contains a biotechnologically produced spike protein (subunit vaccine). This type of vaccine is already established and can also be used safely in immunocompromised individuals.

In addition, the scientists are using bioinformatics approaches to search for synthetic variants of the spike protein that lead to the formation of cross-reactive immune responses. The aim of this project is to ensure that vaccination with the synthetic spike protein also protects against variants of SARS-CoV-2 as well as against other and upcoming coronaviruses.

In cooperation with the GSI Helmholtzzentrum für Schwerionenforschung, HZI researchers are working on improved methods for inactivating viruses for vaccine research. The inactivation of viruses by heat or gamma radiation is a traditional approach for the production of inactivated vaccines. However, this can damage the surface and membrane structures of the viruses, which has a negative impact on the immunogenic effect of the vaccine. The GSI and HZI are now investigating whether radiation with high-energy heavy ions can inactivate SARS-CoV-2 while largely preserving the virus structures.

In the context of the European Commission funded Transvac 2 Consortium (A European Network of Vaccine Research and Development) the Team of Prof. Carlos Guzmán also supports the development of other COVID-19 vaccines by providing services to biotech companies and academic groups.

Vaccine safety

As with all vaccinations, reactions can occur shortly after administration. These are caused by the activation of the immune system. "With vaccines based on mRNA or with vectors like adenoviruses, about half of those vaccinated have local or systemic non-serious side effects, such as chills, headache, fatigue or pain at the injection site. This is a much higher proportion than with many established vaccines. Nevertheless, according to all that is known so far, the vaccines are as safe as other vaccines, and the risk-benefit balance is adequate for the populations for which the vaccines have been approved.", says Prof. Carlos A. Guzmán.

In Germany, the Paul Ehrlich Institute monitors the safety of vaccines. It collects and evaluates reports on suspected cases of adverse reactions and regularly publishes safety reports.

Research news

Vaccination

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Involved research groups

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