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  • Omicron subvariants BA.4 and BA.5 are currently the dominant strains of new COVID-19 cases in the United States.
  • Researchers have found the two subvariants are over 4 times more resistant to mRNA vaccines than earlier strains of Omicron.
  • The study findings suggest that researchers should remain vigilant about new strains of COVID-19 to develop more effective treatments and plan for public health initiatives.

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As of July 13, the Centers for Disease Control and Prevention (CDC) reported that Omicron subvariants BA.5 and BA.4 are the dominant strains of SARS-CoV-2 in the United States, accounting for over 80% of cases.

It’s unclear whether the BA.4 and BA.5 subvariants evolved from the original Omicron variant, as experts believe they likely evolved from the previously dominant BA.2 Omicron variant.

The two new subvariants were initially spotted in South Africa in April and quickly spread around the globe and have a high transmission rate. They carry mutations on their spike protein — the part of the virus that attaches to ACE2 receptors on human cells so they can enter them.

Understanding how current vaccines and treatment options perform against new Omnicron subvariants could inform the development of new therapeutics and help plan public health initiatives.

In a new study recently published in the journal Nature, researchers conducted lab experiments to see how well antibodies from vaccinated individuals can neutralize the new subvariants. The findings show that, when compared to BA.2, BA.4 and BA.5 are at least 4 times more resistant to antibodies in individuals who received mRNA vaccines.

Although the new research shows that immunity against the dominant Omicron subvariants appears to be waning, it’s important to note that mRNA vaccines continue to provide very durable B and T cell-based protection against severe outcomes from COVID-19, including hospitalization and death. In addition, preliminary data shows that natural infection — occurring up to 14 months ago — remains 97% protective against the current Omicron subvariants. In general, T cell immunity from mRNA vaccines remains protective across all COVID-19 variants.

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For the study, the researchers collected blood samples from people who received three doses of an mRNA COVID-19 vaccine. They also collected samples from individuals who received two mRNA COVID-19 vaccines and had previously contracted a non-Omicron SARS-CoV-2 variant.

The researchers then tested antibodies from these individuals against various “pseudoviruses” of the Omicron subvariants. (Pseudoviruses are safe for studying and cannot replicate.)

They found that Omicron BA.2.12.1 — the dominant SARS-CoV-2 variant in the U.S. between May and June — was 1.8 fold more resistant to antibodies from vaccinated and boosted individuals than the BA.2 subvariant.

However, BA.4 and BA.5 were 4.2 times more resistant to antibodies from vaccinated and boosted individuals.

The researchers also tested the pseudoviruses against 21 monoclonal antibody treatments, which are made in a lab and are usually given via infusion to help the immune system against infection. Of the 21 monoclonal antibody treatments, only one remained highly effective against BA.2.12.1, BA.4, and BA.5.

According to the study authors, as the Omicron lineage of SARS-CoV-2 continues to evolve, it is both more transmissible and more evasive to antibodies.

They noted that it is important to remain vigilant when monitoring dominant variants of SARS-CoV-2 but to remain mindful that they emerged randomly and unexpectedly.

When asked about why current dominant Omicron subvariants are better at evading vaccines, Dr. Clarence Buddy Creech II, MPH, director of the Vanderbilt Vaccine Research Program at Vanderbilt University, told Medical News Today:

“As we see subvariants emerge, it is not surprising that they are capable of evading immunity; variants that are easily neutralized by our immune system will have a difficult time becoming the dominant strain now that the vast majority of individuals have been vaccinated or infected with COVID-19.”

Dr. Creech added that future subvariants “may do the same, recognizing that the virus can only change so much before those mutations begin to severely weaken the virus.”

Amira Roess, PhD, MPH, professor of Global Health and Epidemiology at George Mason University, added that we should expect to see more subvariants.

“As microbes evolve they are more likely to mutate in ways that allow them to escape immunity that we have either from vaccines or natural infection.”

– Amira Roess, PhD, MPH

Possible limitations

When asked about the limitations of the study, Dr. Creech noted that the findings may be limited as they only address the role of antibodies produced by individuals and monoclonal antibodies and not the cellular immune system in neutralizing the virus.

He noted, however, that an implication of the study is that current monoclonal antibody therapies may no longer be effective for those at high risk for COVID-19.

Different countries have different immune profiles against COVID-19 due to several factors, including:

  • vaccination rates
  • circulating strains
  • general risk profiles (i.e., age, public safety measures, etc.)

These varying factors mean that BA.4 and BA.5 may affect countries differently. Nevertheless, higher case numbers of BA.4 and BA.5 were recently linked to a small rise in hospitalizations in South Africa, although a slightly lower death rate than the country’s previous Omciron wave.

Countries such as Portugal are seeing a more significant effect from BA.4 and BA.5. Although it has a higher vaccination rate than South Africa, it also has an older population. There, rates of hospitalization and death are similar to those in the first Omicron wave, although still less than those caused by earlier waves.

“It is possible that BA.4 and BA.5 may lead to increased hospitalizations, particularly among the unvaccinated, the immunosuppressed, and those of advanced age. This is why vaccination is so important; while we see cases increasing, we have seen fewer hospitalizations than at other times in the pandemic because of the impact of immunity.”
– Dr. Clarence Buddy Creech II, MPH

When asked about whether BA.4 and BA.5 will lead to more hospitalizations, Dr. Roess said: “We hope that there is enough underlying immunity that we will not see severe illness, and some studies indicate this.”

“Other studies show that severe illness is mainly observed among those who have significant underlying conditions or are of advanced age,” Roess concluded.