The Lancet: BA.1, BA.4, BA.5 and Q.1.1 are resistant to all therapeutic antibodies

Are currently approved antibody therapies for the treatment of patients at high risk of severe COVID-19 disease also effective against virus variants currently circulating? According to a new study by scientists from the German Primate Center (DPZ)-Leibniz Primate Institute and Friedrich-Alexander University Erlangen-Nürnberg, the Omicron sublineage BQ.
1.
1, which is on the rise worldwide
, is resistant to all approved antibody therapies.

Infection with SARS coronavirus-2 (SARS-CoV-2) or vaccination against COVID-19 triggers an immune response that produces neutralizing antibodies to help prevent SARS-CoV-2 reinfection or severe illness
.
Neutralizing antibodies attach to viral spike proteins, providing protection against virus entry into cells
.

Omicron subvariants BA.
1, BA.
4, BA.
5, and Q.
1.
1 have a higher
number of spike protein mutations.
Some of these mutations are escape mutations that allow the virus to escape neutralization
by antibodies.
In addition, resistance to biotechnology-produced antibodies is also developing, either as a preventive measure or as a treatment for the diagnosis of SARS-CoV-2 infection
.
The Omicron sublineage BQ.
1.
1 is the first variant
to be resistant to all antibody therapies currently approved by EMA (European Medicines Agency) and/or FDA (US Food and Drug Administration).

However, certain SARS-CoV-2 variants, particularly the Omicron variant, avoid neutralizing antibodies due to mutations in the spike protein, even in vaccinated or convalescent individuals, causing symptomatic infections
.
This is called immune evasion, and it poses a danger to high-risk groups including the elderly and people with weakened immune systems, for example, due to illness or medication
.

Even after being fully vaccinated, they often fail to produce an immune response
sufficient to protect them from severe disease.
To protect high-risk patients, biotechnology-produced antibodies are used as preventive measures or early treatment
after confirmed SARS-CoV-2 infection.
Spike protein mutations in different SARS-CoV-2 variants develop resistance to individual antibody therapies
.
Therefore, it is important to regularly monitor whether therapeutic antibodies continue to
be effective against currently circulating virus mutations.

A team of researchers from the German Primate Center-Leibniz Primate Institute and the Department of Molecular Immunology at the University of Friedrich-Alexander (Erlangen-Nürnberg) investigated how approved antibody therapies effectively inhibit the currently circulating Omicron subvariant
.
The researchers found that the Omicron subvariant BQ.
1.
1, which is on the rise globally, is resistant to all available antibody therapies
.

"In our study, we mixed non-propagating viral particles carrying the selected viral variant spike protein with different dilutions of the antibody to be tested, followed by the measurement of the amount of
antibody required to inhibit infection in cell cultures.
In total, we tested 12 individual antibodies, 6 of which were approved for clinical use in Europe, and 4 antibody cocktails
.
Prerna Arora, lead author of the study,
explains.

The researchers found that the Omicron subvariant BQ.
1.
1 could not be neutralized
by a single antibody or antibody cocktail.
In contrast, the currently dominant Omicron subtype BA.
5 is still neutralized
by one approved antibody and two approved antibody cocktails.

"Given the high-risk patients, we are very concerned that the Omicron subvariant BQ.
1.
1 is resistant to all approved antibody therapies
.
Especially in areas where BQ.
1.
1 is widely transmitted, doctors should not rely solely on antibody therapy when treating patients at high risk of infection, but should also consider the use of other drugs such as paxlovid or molnupiravir," study leader Markus Hoffmann commented on the findings
.

The discovery that the Omicron subvariant BQ.
1.
1 is already resistant to a new antibody therapy soon to be approved in the United States underscores the importance of
developing new antibody therapies against COVID-19.

"As antibody resistance to SARS-CoV-2 variants continues to increase, there is a need to develop new antibody therapies
specifically targeting current and future viral variants.
Ideally, they should target regions of the spike protein that have little possibility of escaping mutations," concludes
Stefan Pöhlmann, head of the Department of Infection Biology at the German Primate Center-Leibniz Primate Institute.

References:

Omicron sublineage BQ.
1.
1 resistance to monoclonal antibodies