SARS-CoV-2 is undergoing mutations. Does the vaccine still work？

According to the statistics of the World Health Organization (WHO), the cumulative number of people infected by SARS-CoV-2 in the world has exceeded 27 million. At the same time, the research and development of drugs and vaccines for COVID-19 in the biomedical industry are also making rapid progress. At present, a number of COVID-19 vaccine candidates and neutralizing antibody therapies have entered the phase 3 clinical trials. However, we know that the virus genome produces mutations, and the SARS-CoV-2 is no exception. At present, there are more than 95,000 genome sequences in the SARS-CoV-2 database of GISAID. One worry is that the mutation of the SARS-CoV-2 will invalidate the COVID-19 vaccine currently under development?

Is the genomic mutation of the SARS-CoV-2 fast?

The SARS-CoV-2 is a single-stranded RNA virus containing nearly to 30,000 bases. Compared with DNA viruses, RNA viruses are easier to introduce mutations during the replication process. However, compared with the coronavirus that causes certain common colds and the HIV virus that causes AIDS, the mutation rate of the SARS-CoV-2 is not high.

As we know, the many current antiviral therapies are not effective against the SARS-CoV-2. Nucleoside analogs are used in many of these antiviral therapies. They can replace the nucleosides that make up the RNA and insert them into the RNA sequence of the virus during the process of RNA replication, thereby interfering with RNA replication. The error correction mechanism of the SARS-CoV-2 has caused most nucleoside antiviral therapies to "return without success", and this mechanism has also made the genome of the SARS-CoV-2 more stable. Dr. Emma Hodcroft, a molecular infectious disease scientist at the University of Basel, said that the genome of the SARS-CoV-2 accumulates two single-base mutations approximately every month. This mutation rate is half times that of the coronavirus that causes the common cold, 1/4 of the HIV virus.

Will the mutation make the vaccines invalid?

In a paper published on PNAS a few days ago, researchers analyzed 18,484 SARS-CoV-2 genomes. They found that the sequence of the spike protein encoding SARS-CoV-2 is very stable. The most significant mutation is the D614G mutation, which appeared at the earliest. In the spike protein of the new coronavirus, an aspartic acid (D) occupies position 614. After mutation, the spike protein at this position becomes glycine (G). The SARS-CoV-2 that carries this mutation currently dominates the world. However, this mutation is located at the junction of the S1 subunit and S2 subunit of the spike protein and is not easily recognized by antibodies. Therefore, the researchers speculate that this mutation will not affect the binding of the antibody to the spike protein.

In addition to the D614G mutation, the second most frequent gene mutation in the spike protein is a synonymous mutation (the gene sequence has been changed, but the amino acid produced has not been changed), and the frequency is only 1.96%. The comparison of different spike protein sequences showed that the SARS-CoV-2 sequence found in infected patients has only 0.55 base mutations in the spike protein compared with the benchmark sequence. These data mean that there are not a large number of genetic mutations that can make vaccines ineffective against the viruses currently existing in the world.

Will mutations that make vaccines ineffective occur in the future?

Current scientific research shows that the genetic mutations that have been produced in the SARS-CoV-2 will not have a significant impact on the effects of neutralizing antibodies and COVID-19 vaccines. However, historical experience has shown that drug resistance can occur, and bacterial antibiotic resistance is currently a major challenge in the global health field. So, is it possible for the SARS-CoV-2 to gradually gain the ability to evade the immune response triggered by the vaccine like drug-resistant bacteria?

Although scientists have discovered SARS-CoV-2 strains that can evade the effects of certain neutralizing antibodies, they are still very rare in the global population. Since most people in the global population have no immunity to the SARS-CoV-2, their immune system cannot yet exert selective pressure on the reproduction of the SARS-CoV-2. This means that these genetic mutations that are potentially resistant to vaccines cannot yet stand out.

It is true that if the COVID-19 vaccines successfully improve the immunity of people around the world to the SARS-CoV-2, under the selective pressure of immunity, the number of SARS-CoV-2 strains carrying immune escape gene mutations may gradually increase. Therefore, scientists still need to closely monitor the emergence of new genetic mutations.