Immunity gained from original strain not adequate against later subvariants

People infected with the original version of the COVID-19 Omicron variant virus are vulnerable to reinfection by later mutated subvariants of Omicron, including BA.4, BA.5 and BA.2.12.1, according to a new study published in the journal Nature last week.

The researchers warned that vaccine boosters that are being developed based on the original Omicron strain may not achieve broad-spectrum protection against the new Omicron subvariants.

The natural immunity gained by being infected with the early version of Omicron also does not provide adequate protection against the latest strains, the study found, thus debunking the controversial notion that the Omicron variant is a "natural vaccine" with mild symptoms and that people should proactively get infected in order to gain immunity against future viral strains.

BA.4, BA.5 and BA.2.12.1 are newly discovered Omicron strains that have shown greater immunity evasion and transmissibility than their predecessors. They have recently become the dominant strains in the United States, South Africa and some European countries, but the total number of new cases attributed to these strains is smaller than the massive wave of Omicron infections that washed over the world during the winter of 2021.

Sunney Xie Xiaoliang, a scientist behind the study and a biochemical professor at Peking University, told Beijing-based science outlet the Intellectual that BA.4, BA.5 and BA.2.12.1 all share a mutation called L452, while BA.4 and BA.5 also have an additional mutation called F486V.

These mutations played a key role in increasing these subvariants' ability to evade antibodies from the original Omicron variant, thus leading to breakthrough infections, he said.

Xie said it is still necessary to develop booster vaccines that can provide broad-spectrum protection against a range of Omicron strains. This may require breakthroughs in protein or mRNA vaccines, but designing a broad-spectrum vaccine is generally very difficult, he added.

As for treatments, Xie said most monoclonal antibody drugs have lost their effectiveness against the Omicron subvariants due to the new mutations, save for Bebtelovimab and Evusheld.

Scientists may need to find new combinations of antibodies that can target the new strains, he said. One combination candidate, namely SA58 and SA55, has displayed high potency against all Omicron subvariants, but more research is needed to confirm their effectiveness.

"It is easy to find an antibody that is highly potent in neutralizing the virus, but the key is to find an antibody that is hard for the new subvariant to evade," he said.

These antibodies can also be turned into safe preventive medications for the Omicron variant, but the downside is such treatment is currently very expensive, he said. However, the cost can be lowered to a manageable level if production scales up or if the treatment is only used among highly vulnerable demographics, such as those who are immune-compromised, he added.