Will the current vaccines be effective against the new variants?


Q: If not, what happens, do we need a new, different vaccine?”

A: The vaccines developed thus far will likely have efficacy against the different SARS-CoV-2 variants although the level of efficacy may be reduced to the South Africian variant (B.1.351).

More clinical data will be needed to understand the levels of protection against new variants as they arise. Scientists have started rapidly generating new vaccines specifically against emerging viral variants that can be used as boosters to the current vaccine regimes.

Coronaviruses are RNA viruses. They sometimes make mistakes when they make copies of themselves. Many of the substitutions in the viral genome, have no effect. Sometimes the mistakes confer a selective advantage to the virus. For example, certain changes in the sequence of the spike protein can help the virus bind to the human cells better and become more transmissible. Mistakes can also accumulate overtime and eventually create different viral variants.

These “mistakes” are referring to substitutions or mutations in the genetic sequence from the original strain that was discovered in Wuhan, China. The process of changing the viral genetic material over time is a normal part of the coronavirus life cycle. Unfortunately, the widespread nature of SARS-CoV-2 has allowed the virus to accumulate a number of mutations in different geographical locations over time leading to the emergence of several variants.

There are multiple variants currently: South Africa (B.1.351), Brazil (B1.1.28), and the UK (B1.1.7). These variants contain mutations in the spike protein which is the protein that the virus uses to get inside our cells. SARS-CoV-2 B.1.1.7 variant has eight mutations located in the spike protein. The B.1.351 variant has ten mutations located in the spike protein. The spike protein is also the sequence that the vaccines are based on because immune responses against this protein can stop the SARS-CoV2 virus from entering our cells.

The vaccines in clinical development were created using the spike sequence from the originally identified strain in Wuhan, China. This spike protein sequence is similar enough to provide some degree of protection against these new strains. In experiments in a culture dish, scientists have taken serum from the blood of people that were vaccinated with the Pfizer or Moderna vaccine. The serum contains the antibodies generated by the immune response generated to the vaccine. They tested the ability of those antibodies to stop the new viral variants from infecting a cell- this is called neutralizing ability. Scientists have found that the neutralizing antibodies in the serum DOES stop the viruses containing the spike mutations from entering the cells however the degree of protection was reduced to SOME of the strains.

When experiments were done using the UK variant B1.1.7, no differences in viral inhibition were observed compared to other viral variants. Yay! Experiments with the South Africian variant B.1.351 did result in a 6 fold reduction of neutralizing antibodies however the levels of neutralizing antibodies were still high enough to be still protective.
These experiments were in cell culture dishes. Data in people is still needed to understand what is the decrease in protection/efficacy. For example, the vaccines may not be as good at preventing asymptomatic spread of some emerging variants.

Moderna announced that they are planning to test another boost dose of their vaccine to see if it increases the levels of neutralizing antibodies. They will also develop a specific vaccine against the South Africian variant B.1.351 to test as a booster to the existing vaccine series.They will do this by changing the mRNA contained within the vaccine to the sequence of the spike protein that is in the South Africian B.1.351 variant. This can happen relatively quickly and they will proceed with phase I trials. They will likely not have to complete phase III trials again.

In breaking news, Novavax vaccine, a protein plus adjuvant vaccine based on the sequence of the spike protein, was recently shown to be effective against the UK variant and had reduced efficacy against the South African variant. In phase 3 trials in the UK where the UK variant was over 50% of cases, the vaccine’s efficacy was 89.3%. However in phase 2 trials in South African where the B.1.351 variant was 90% of cases, the vaccine efficacy was 60%. It was still protective, but the efficacy was reduced. Data from that trial also demonstrated that prior infection with SARS-CoV2 was not completely protective of subsequent infection with the South Africian variant. But vaccination did provide significant protection from SARS-CoV2 B.1.351 although reduced compared to other variants. Novavax is also developing new vaccines against the emerging strains to be used as a booster or in combination with its current vaccine. They will simply use the sequence of the spike protein in the emerging variants rather than or in addition to the sequence of the original spike protein.

Antigenic drift is a word used for when a virus changes so much over time that it no longer is recognized by the immune system. To stop antigenic drift and development of additional viral variants, we need to lower the rates of transmission using #SMARTS practices. When we reduce viral transmission we also reduce levels of viral evolution. This is also why our world needs to come together. If one country is fully vaccinated but other countries are not, a new strain can emerge that the current vaccines do not cover. Another vaccine will have to be designed and distributed.

Neutralizing antibody manuscript using different viral variants

Information on Moderna preclinical data and clinical development path

CDC information on different viral variants

Novavax press release

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