A SARS-CoV-2 vaccine candidate based on B.1.351 spike trimer shows broad neutralizing capability

Researchers tested a vaccine candidate in mice with up to three doses and found it produces high levels of antibodies against both SARS-CoV-2 variants of concern and the original virus strain.

The emergence of several new mutations of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to concerns about increased transmissibility of the virus and the ability of vaccines to protect against them. Some studies point to lower efficacy of vaccines to the new strains compared to the original strain.

For example, many of the approved vaccines show a lower efficacy against the B.1.351 strain, which was first detected in South Africa, compared to the original strain. The antibody levels against this variant in vaccinated individuals were much lower than those against the original variant.

The inability of vaccines to effectively neutralize different variants could lead to the continued spread of the virus, which will allow it to continue mutating and causing an increasing number of infections and deaths.

In a paper published on the bioRxiv* preprint server, researchers report a new vaccine candidate using a modified B.1.351 spike protein and tested its efficacy in mice.

Testing new vaccine candidate

The team tested sera from eight convalescent patients infected with the original strain and found the antibody levels against the B.1.1.7 (or UK) strain to be similar to antibodies against the original strain, but levels were much lower for the B.1.351 and P.1 (or Brazilian) strains.

They produced trimerized spike protein antigens based on the original strain and the B.1.351 strain, which contained the three mutations in the receptor-binding domain (RBD): K417N, 87 E484K, N501Y.

The authors immunized mice with two doses of the original spike trimer, a second booster dose with the B.1.351 spike trimer, two doses of the B.1.351 spike trimer, or two doses of both mixed together. They tested the immune response about two weeks after the second dose.

They found neutralizing antibody levels against B.1.351 and P.1 to be the highest in the animals that received two doses of the B.1.351 trimer or the mixed doses. However, receiving only a second dose of the B.1.351 trimer did not seem to increase antibody levels against these variants. All vaccinated groups were also able to effectively neutralize the original strain and the B.1.1.7 strain.

Next, the authors tested antibody levels using a third booster dose. The levels against the B.1.351 and P.1 increased for the case when the first dose was a spike trimer, but did not vary much for cases where the first dose was the B.1.351 trimer. However, the antibody levels against the variants did not increase when two doses of the spike trimer were given initially.

Broad neutralizing capability

Thus, the B.1.351 based spike trimer induced high levels of neutralizing antibodies against the different variants of concern, including the original virus strain. This contrasts with another mRNA-based vaccine candidate based on the B.1.351 spike protein, which showed much lower antibody levels against the original strain.

The authors think the broad neutralizing capability of the B.1.351 trimer vaccine candidate is likely because of the presence of the three mutations seen in this strain in the RBD (neutralizing the variants) plus the original sequences in the N-terminal domain and the S2 subunit, which produce antibodies against the original strain. This adds to emerging evidence that antibodies to the N-terminal domain are equally important in neutralizing the virus.

The results also suggest that giving a booster dose after the initial two doses can increase antibody levels against the variants. If this is indeed confirmed to be true in future studies, it means it could provide greater flexibility in providing booster doses. However, the long-term effects of revaccination, with the same type and different type of vaccine, will still need to be studied.

An initial dose with the original spike trimer vaccine candidate and later doses with the B.1.351 spike trimer did not seem to increase the antibody levels against the variants much. This suggests priming with the original COVID-19 vaccines may cause the immune system to respond preferentially to the epitopes in the original vaccine and less to the newer epitopes in the booster doses. This is something similar to what is seen in other virus vaccinations such as influenza and dengue.

In addition, further studies are needed to understand the use of adjuvants in doses as well as how a combination of vaccines with different technologies may affect us in the long term.

*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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