CureVac COVID-19 vaccine protects mice against emerging SARS-CoV-2 mutations

The CVnCoV mRNA vaccine showed neutralized antibody levels and mice that were completely immune to the B.1.351 variant. Viral genomes were not seen in oral, lung, or brain swabs.

Study: CVnCoV protects human ACE2 transgenic mice from BavPat1 B ancestor and expression of B.1.351 SARS-CoV-2.  Image credit: NIAID

A number of vaccines have been approved or are being developed to combat COVID-19 pandemics. Many of these vaccines are based on messenger RNA (mRNA) technology, which works by ordering cells to produce the virus’s spike proteins.

As the pandemic continues, several variants of the acute acute coronavirus 2 (SARS-CoV-2) respiratory syndrome have emerged in different parts of the world. These variants have many mutations on the virus’s spike proteins, particularly the receptor binding domain (RBD).

Some of these mutations appear to increase binding affinity to host cells, and antibodies from pre-existing diseases do not neutralize the variants as effectively, which may lead to increased transmission.

Although variant B.1.1.7, first found in the United Kingdom, appears to be neutralized by vaccine-induced antibodies, variant B.1.351 was resistant to sera convalescent and antibodies from vaccinated individuals. Variables that escape neutralization can become strong layers and require different vaccines.

Although there is some data on over-necrosis from sera of mRNA vaccines, in vivo studies in animal models are still pending. In a new study published on the bioRxiv * preprint server, researchers from the German Friedrich-Loeffler-Institut report the efficacy of the CVnCoV mRNA vaccine to the early SARS-CoV-2 strain and the B.1.351 strain in a mouse model.

Testing the efficacy of vaccines in mice

The researchers used an ACE2 model expressing a mouse and vaccinated with two doses of the CVnCoV vaccine 28 days apart. After four weeks of the second dose, the animals were challenged with SARS-CoV-2 614G version or B.1.351 version.

Sera from vaccinated mice showed strong IgG levels at days 28 and 55 after the first dose. The levels in the latter samples were significantly higher than those at day 28. The antibody levels ingested were significantly higher than those stimulated by the use of direct preparation. Formal-enhanced SARS-CoV-2 (FI-Virus).

The neutralization levels of the B.1.351 variants were lower than the neutralization levels of the D614G variant, but the vaccine-induced levels were significantly higher than those caused by just the FI-Virus.

The authors conducted the next study on whether CVnCoV could protect the animals from SARS-CoV-2. The vaccinated mice were challenged with high doses of the two variant viruses. Four days after infection with the 614G version, the mice on the control groups began to die. The B.1.351 variant was delayed, with approximately 20% of the mice alive after 10 days. Although it is not clear why the variant B.1.351 causes different disease progression, mutations appear to cause a change in disease characteristics.

In contrast, the mice with CVnCoV vaccine were completely immune, with no compliance with the disease or showing any signs of the disease. Mice vaccinated with the FI-Virus showed weight loss and symptoms of distress.

CVnCoV protects against version B.1.351

Following the CVnCoV vaccination, D614G viral genomes were not visible in oral swabs from the animals. In addition, there were very few genome copy numbers in the upper respiratory tract of some animals, indicating that the vaccine completely protected the animals from the virus. The team also tested for the virus genome in the brain and lungs and found no viruses in these organs.

Similarly, very low virus genome numbers were observed for the B.1.351 variant, suggesting that the vaccine may protect against this variant and prevent the spread of the virus to other organs.

Thus, the CVnCoV vaccine is able to protect the mice from two strains of the SARS-CoV-2 virus, including B.1.351. In addition, the vaccine can prevent viral reproduction in the brain and lungs.

The protection is due to high levels of anti-RBD and neutralizing antibodies, but it is not clear whether the benefit is directly due to the antibodies. Vaccines can stimulate a broad immune response, including cellular responses, antibody-dependent cytotoxicity, and tissue protective immune effects, which may explain the beneficial effects.

The CVnCoV vaccine has also been shown to stimulate Th1 immunity and T cell responses in mice, which may also protect against disease when antibody levels fall. In the animals of this study, the authors observed protection against infection even when neutralizing low antibody levels. This suggests that either other immune processes aid in defense or that low levels of antibody are sufficient to protect against the B.1.351 mutation.

* Important message

bioRxiv publish preliminary scientific reports that are not peer-reviewed and, therefore, should not be seen as final, guiding health-related clinical practice / behavior, or be treated as information established.

.Source