CureVac's COVID-19 vaccine protects mice against emerging SARS-CoV-2 variants

The CVnCoV mRNA vaccine showed neutralizing antibody levels and completely protected mice infected with the B.1.351 variant. No viral genomes were seen in oral swabs, lungs, or brain.

Several vaccines are approved or under development to combat the COVID-19 pandemic. Many of these vaccines are based on messenger RNA (mRNA) technology, which works by instructing cells to make the virus spike protein.

As the pandemic continues, several variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged in different parts of the globe. These variants have many mutations on the virus spike protein, mainly the receptor-binding domain (RBD).

Some of these mutations seem to increase binding affinity to host cells, and antibodies from previous infections do not neutralize the variants as efficiently, which could lead to increased transmissibility.

Although the B.1.1.7 variant, first discovered in the United Kingdom, appears to be neutralized by vaccine-induced antibodies, the B.1.351 variant was resistant to convalescent sera and antibodies from vaccinated individuals. Variants that escape neutralization may evolve into dominant strains and need different vaccines.

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

Testing vaccine efficacy in mice

The researchers used an ACE2 expressing mouse model and vaccinated it 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 variant or the B.1.351 variant.

Sera from vaccinated mice showed strong IgG levels on 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 induced were significantly higher than those induced using only a formalin-inactivated and adjuvanted SARS-CoV-2-preparation (FI-Virus).

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

The authors next studied if CVnCoV could protect the animals from SARS-CoV-2. The vaccinated mice were challenged with high doses of both virus variants. Four days after infection with the 614G variant, the mice on the control groups started dying. The B.1.351 variant had a delayed disease onset, with about 20% of the mice surviving after 10 days. Although it is not clear why the B.1.351 variant causes a different disease progression, mutations likely cause a change in disease characteristics.

In contrast, the mice immunized with CVnCoV were wholly protected, with none succumbing to the infection or showing any symptoms of the disease. The mice immunized with the FI-Virus showed weight loss and signs of distress.

CVnCoV protects against B.1.351 variant

After CVnCoV vaccination, no D614G viral genomes were seen in oral swabs from the animals. In addition, there were very few genome copy numbers in the upper respiratory tract of some animals, indicating vaccination completely protected the animals from the virus. The team also tested for the virus genome in the brain and lungs and did not find any virus in these organs.

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

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

The protection is because of high levels of anti-RBD and neutralizing antibodies, but it is not clear if the benefit is only because of the antibodies. Vaccines can induce a broad immune response, including cellular responses, antibody-dependent cytotoxicity, and antibody-mediated innate immune effector functions, which may explain the beneficial effects.

CVnCoV vaccination has also shown to induce Th1 immunity and T cell responses in mice, which may also protect against infection when antibody levels drop. In the animals of this study, the authors observed protection against infection even when neutralizing antibody levels were low. This suggests either other immune processes help with protection or low antibody levels are enough to protect against the B.1.351 variant.

*Important Notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Lakshmi Supriya

Written by

Lakshmi Supriya

Lakshmi Supriya got her BSc in Industrial Chemistry from IIT Kharagpur (India) and a Ph.D. in Polymer Science and Engineering from Virginia Tech (USA).

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