After quickly spreading to many countries and becoming the dominant strain in circulation within a very short time after Omicron was designated as a variant of concern on November 26, 2021, the Omicron sub-lineage BA.2 is now following the in the footsteps of BA.1 in many countries, including Denmark, the Philippines and South Africa in the past few weeks. This suggests that the sub-lineage BA.2 has a “selective advantage” over the original Omicron variant — BA.1 sub-lineage.
Cluster of sequences
The BA.2 has a “cluster of sequences that share many of the same mutations as the ‘original’ Omicron (BA.1) but is missing some mutations and has some other new ones,” Dr Emma Hodcroft, co-developer of Next Strain tweeted.
A few studies are now discovering that BA.2 sub-lineage has even higher propensity to spread among people and has the ability to infect people who have been fully vaccinated and/or previously infected by escaping from neutralising antibodies induced by vaccination or infection.
A study was carried out in 24 individuals who were fully vaccinated and received a booster shot of the Pfizer vaccine and eight participants who were naturally infected with SARS-CoV-2. In people who have been fully vaccinated with the Pfizer vaccine, compared with the Wuhan strain, there was a 23-fold and 27-fold reduction in median neutralising antibody titres to BA.1 and BA.2, respectively. The results were posted in a preprint server medRxiv on February 7. Preprints are yet to be peer-reviewed.
Good protection
Two weeks after a booster shot, the reduction in median neutralising antibody titres to BA.1 and BA.2 was only 6.1-fold and 8.4-fold, respectively, compared with the Wuhan strain. The neutralising antibody titres to BA.2 were about 1.4-fold lower than BA.1. From a public health perspective, the study found that when vaccinated individuals were infected with BA.1, they developed robust neutralising antibodies against BA.2. So BA.1 infection in vaccinated people offered good protection against BA.2.
The differences in protection to BA.1 and BA.2 in both fully vaccinated and those who received a booster shot were not sufficiently different to explain why BA.2 is spreading widely in many regions of the world.
Difference in resistance
Another study by a team led by Dr. Dan H. Barouch from the Center for Virology and Vaccine Research, Boston, Massachusetts, U.S. found that both BA.1 and BA.2 had comparable ability to escape neutralising antibodies in people who are either fully vaccinated or naturally infected. Using a panel of 19 neutralising monoclonal antibodies as probes, the researchers found that like BA.1, BA.2 also totally or severely resisted 17 of 19 monoclonal antibodies but with certain critical differences. BA.1 was more resistant to one class of antibodies than BA.2, while BA.2 was more resistant to another class of antibodies tested. The results were posted as a preprint in bioRxiv sever on February 9.
“These findings have important public health implications and suggest that the increasing BA.2 frequency in the context of the BA.1 surge is likely related to increased transmissibility rather than enhanced immunologic escape,” Dr. Dan H. Barouch and others write.
More infectious
Another study carried out in over 8,500 Danish households that were infected with the Omicron variant by a team led by Frederik Plesner Lyngse from the Danish Ministry of Health, Copenhagen, Denmark, found that unvaccinated, fully vaccinated and those who have received a booster shot were more susceptible to infection by BA.2 than BA.1. In short, BA.2 was more infectious than BA.1.
Surprisingly, the “relative increase in susceptibility was significantly greater in vaccinated individuals compared to unvaccinated individuals which points towards immune evasive properties of the BA.2 conferring an even greater advantage for BA.2 in a highly vaccinated population such as Denmark,” the researchers note.
Unvaccinated people infected with BA.2 had greater transmissibility than those who were infected by BA.1. But this difference between BA.1 and BA.2 was not seen in people who have been fully vaccinated or among those who have taken a booster shot. The results are posted on a preprint server medRxiv on January 30, this year.
“We conclude that Omicron BA.2 is inherently substantially more transmissible than BA.1, and that it also possesses immune-evasive properties that further reduce the protective effect of vaccination against infection, but do not increase its transmissibility from vaccinated individuals with breakthrough infections,” the Danish researchers write.
Hamster experiments
Another study posted as preprint in bioRxiv found that in cell culture, BA.2 had higher ability to replicate in human nasal epithelial cells and also the ability to fuse with cells was higher.
Importantly, infection experiments using hamsters showed that BA.2 is more pathogenic than BA.1, the authors write.
In January, another sub-lineage of Omicron — BA.3 — was detected. It has 33 mutations in the spike protein. But none of the mutations are novel. Of the 33 mutations, 31 are seen in BA.1 as well, and the remaining two are seen in BA.2.
Compared with BA.1 and BA.2, the BA.3 sub-lineage is marked by slow spread. One reason could be the absence of six mutations seen in BA.1, according to an article in the BMJ.
- A few studies are now discovering that BA.2 sub-lineage has even higher propensity to spread among people and has the ability to infect people who have been fully vaccinated and/or previously infected by escaping from neutralising antibodies induced by vaccination or infection.
- While BA.1 infection in vaccinated people offered good protection against BA.2, the differences in protection to BA.1 and BA.2 in both fully vaccinated and those who received a booster shot were not sufficiently different to explain why BA.2 is spreading widely in many regions of the world.
- Unvaccinated people infected with BA.2 had greater transmissibility than those who were infected by BA.1. But this difference between BA.1 and BA.2 was not seen in people who have been fully vaccinated or among those who have taken a booster shot.
- In January, another sub-lineage of Omicron — BA.3 — was detected. It has 33 mutations in the spike protein. But none of the mutations are novel. Of the 33 mutations, 31 are seen in BA.1 as well, and the remaining two are seen in BA.2.
