BA.2.75 Omicron Subvariant: Key Facts and Updates

The BA.2.75 Omicron subvariant emerged in mid-2022 and has rapidly spread across multiple regions worldwide, raising concerns about its potential impact on public health1 . This subvariant carries numerous mutations that may enhance its ability to evade immunity and increase transmissibility, although its severity remains unclear2 . Understanding the relationship of BA.2.75 to other Omicron subvariants and its epidemiological trajectory, especially in the United States, is critical for guiding ongoing surveillance and vaccine strategies1 2.

Despite BA.2.75's ability to evade immunity, vaccines continue to protect against severe disease, underscoring the importance of vaccination and booster campaigns. 119

BA.2.75 and Other Omicron Subvariants

BA.2.75 is a descendant of the Omicron BA.2 lineage, which was globally dominant in early 20223 . Phylogenetic analyses confirm that BA.2.75 evolved from BA.2 and is genetically distinct from the BA.4 and BA.5 sublineages, which have separate evolutionary paths3 4. Each of these subvariants harbors unique spike protein mutations that influence their transmissibility and ability to evade immune responses5 6.

The BA.2.75 subvariant carries multiple mutations in the spike protein, notably G446S and N460K within the receptor-binding domain (RBD), which enhance receptor binding affinity and contribute to immune escape3 7. Additionally, mutations in the N-terminal domain (NTD) overlap partially with those found in BA.4 and BA.5, further supporting its immune evasion capabilities7 8. Some BA.2.75 sublineages, such as CH.1.1 and BN.1, have shown increased prevalence, suggesting ongoing adaptation7 .

Neutralization studies reveal that BA.2.75 and its descendants partially evade immunity induced by vaccination or prior infection, increasing the risk of breakthrough infections5 9. However, vaccines continue to offer substantial protection against severe disease caused by BA.2.75 infections5 9. Clinical data indicate that infections with BA.2.75 generally result in mild upper respiratory symptoms, especially in vaccinated individuals, consistent with other Omicron subvariants10 11.

Key characteristics of BA.2.75 and related subvariants include:

• Origin from the BA.2 lineage with distinct evolutionary divergence from BA.4 and BA.53 4.
• Spike protein mutations that increase receptor binding and antibody evasion3 7.
• Partial immune escape leading to reduced neutralization by vaccine-induced antibodies5 9.
• Mild clinical presentation in vaccinated populations10 11.
• Expansion of certain sublineages like CH.1.1 and BN.1 with enhanced immune evasion or receptor affinity7 .

BA.2.75 has numerous mutations, shows rapid growth, and may have increased transmissibility, but its severity remains unclear. It may partially resist vaccines and carries mutations that enhance immune escape, making it a subvariant to monitor closely. 1

The evolving spike protein mutations in BA.2.75 and its sublineages underscore the virus's ongoing adaptation to human immunity. This highlights the importance of updating vaccine formulations to maintain effectiveness against emerging variants.

Recent preclinical studies of updated vaccines targeting BA.2.75.2, a descendant sublineage, demonstrate promising immunogenicity and safety profiles in animal models. For example, the AVX/COVID-12 vaccine updated to express the BA.2.75.2 spike protein (V-BA) elicited strong neutralizing antibody responses against multiple Omicron subvariants, including BA.2.75.2, XBB.1.5, and JN.1, while maintaining a good safety profile12 . These findings support the potential for variant-adapted vaccines to enhance protection amid ongoing viral evolution.

BA.2.75 Spread in the United States

The epidemiological dynamics of BA.2.75 in the United States remain uncertain. While BA.5 and its descendants continue to dominate SARS-CoV-2 circulation in the U.S. and many other countries as of late 2023, BA.2.75 and its sublineages have shown increasing prevalence in parts of Asia and Europe13 7. In the U.S., BA.2.75's prevalence has been noted to be highest in regions like New York and New Jersey, where it accounts for approximately 2.4% of new infections, though it has not yet caused a surge comparable to BA.514 13.

BA.2.75 carries mutations that enhance receptor binding and immune evasion, potentially allowing it to infect individuals with prior immunity from vaccination or previous infection3 5. However, real-world data on its transmissibility and clinical severity remain limited, and vaccines still provide substantial protection against severe outcomes9 11.

The competitive interaction between BA.2.75 and other Omicron subvariants, particularly BA.5, will largely determine the future course of COVID-19 waves in the U.S. and globally15 16. Viral spread and variant dominance vary by region due to differences in population immunity, behavior, and public health measures17 11. Laboratory and animal models, while informative, have limitations in predicting variant fitness and spread in human populations18 19.

“The epidemiological trajectory of BA.2.75 is uncertain due to limited real-world data, and its spread depends on complex interactions with other variants and population immunity.”

— Expert consensus21

Public health authorities emphasize the need for ongoing genomic surveillance and immunological studies to monitor BA.2.75 and emerging subvariants to inform timely response strategies16 11. Some countries with high immunity levels have reported rising BA.2.75 infections, suggesting partial immune escape and the potential for future waves7 20.

Factors influencing BA.2.75's epidemiological impact include:

• Continued dominance of BA.5 and its descendants in many regions13 17.
• Regional variation in variant prevalence driven by immunity and behavior17 11.
• Documented immune escape by BA.2.75 subvariants, varying by prior immunity and vaccine type5 8.
• Limited real-world data on transmissibility and clinical severity21 11.
• Importance of genomic and immunological surveillance to detect shifts in variant dominance15 16.

“Vaccines and prior infections still provide substantial protection against severe disease caused by BA.2.75, despite its immune escape capabilities.”

— Clinical data synthesis11 9

Ongoing research is assessing vaccine effectiveness and cross-protection against BA.2.75 and its sublineages. Updated vaccines targeting BA.2.75.2 have shown promising neutralizing antibody responses in preclinical models, suggesting potential benefits of variant-adapted immunization strategies12 .