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Most therapeutic antibodies for treating COVID-19 patients do not inhibit the emerging omicron submutants

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The Omicron subvariants BA.1 and BA.2 of SARS-CoV-2 dominated the pandemic of COVID-19 in early 2022. In many countries, these viruses are now being defeated by new subvariants, with BA.5 being responsible for the current rise. Number of cases in Germany. However, for now, did the “new” Omicron subvariants BA.2.12.1, BA.4, and BA.5 acquire biological properties that allow for more efficient transmission, or are blocked by antibodies? It is almost unknown if it is inefficient to be done. “Old” Omicron subvariants BA.1 and BA.2.

Research by researchers at the German Priest Center (DPZ)-Most of the therapeutic antibodies available to treat patients with COVID-19, according to colleagues at the Leibniz Primate Institute and Hannover Medical College and Friedrich-Alexander University Arlangen-Nürnberg University. Does not inhibit BA.2.12.1, BA.4, and BA.5 at all, or only reduces its efficacy. The antibody bebutellobimab constitutes the only exception because it blocked all mutants tested with high efficiency. In addition, this study found that Omicron’s subvariants BA.2.12.1, in particular BA.4 and BA.5, were predecessors BA.1 and BA.1 by antibodies produced after vaccination or subsequent infection. It shows that it is more severely inhibited than 2. Therefore, BA.2.12.1, BA.4, and BA.5 are antigenic escape mutants. Pass-through infection with the “old” Omicron submutant provides limited protection against infection with the “new” submutant (lancet infection).

The new SARS-CoV-2 mutant appears due to an error during viral genome replication. Therefore, the virus acquires mutations that alter viral proteins such as surface proteins, spikes, which are the central targets of antibody responses. If mutations reduce the recognition of spike proteins by antibodies, such variants are further proficient in spreading among people with pre-existing immunity due to vaccination or past infections.

Infection researchers at the German Primate Center specialize in the analysis of SARS-CoV-2 inhibition by antibodies. In collaboration with colleagues at Hannover Medical College and Friedrich-Alexander University Alangen-Nuremberg, we investigated the inhibition of SARS-CoV-2 omicron submutants BA.2.12.1, BA.4, and BA.5 by antibodies. BA.2.12.1, BA.4, and BA.5 (the latter two subvariants have the same peplomer) are becoming predominant in some countries, with BA.5 being the most recent case in Germany. It is the main cause of the increase.

A team including Prerna Arora, Markus Hoffmann, and Stefan Pöhlmann of the German Primate Center was able to at least partially inhibit BA.2.12.1, BA.4, and BA.5 of the 10 therapeutic antibodies studied. Found that there are only two. The only antibody, bebutellobimab (LY-CoV1404), effectively blocked infection by all Omicron submutants.

These results support the trends already seen in previous studies. Omicron subvariants are not perceptibly inhibited by most therapeutic antibodies, and there are a small number of antibodies that frequently inhibit in a subvariant-specific manner. Therefore, it is important to develop new antibodies to prepare for future submutants. “


Lead author of the study, Plana Arora

Antibodies from unvaccinated individuals infected with the Omicron submutant BA.1 or BA.2 in the spring of 2022 neutralized BA.2.12.1 with similar efficiency, but BA.4 and BA.5. Wasn’t much more powerful against. Therefore, a previous BA.1 or BA.2 infection may provide little protection against subsequent BA.4 or BA.5 infections. Antibodies induced by three immunizations with the BioNTech / Pfizer mRNA vaccine blocked all Omicron submutants. However, the efficiency of inhibition was lower than that measured with the virus circulated early in the pandemic, and inhibition of BA.2.12.1, BA.4, and BA.5 was compared to BA.1 and BA. The efficiency was low. 2.2. Similar results were obtained for antibodies induced by vaccination and breakthrough infections. This so-called hybrid immunity resulted in high overall neutralizing activity against all variants tested, but inhibition of BA.2.12.1, BA.4, and BA.5 was significantly reduced. ..

“BA.2.12.1, especially BA.4 and BA.5, are antibody avoidance mutants. Vaccination protects against serious diseases induced by these mutants, but previously circulating mutations. Defensive efficiency can be slightly less than measured with the body, “Markus Hoffmann concludes. , Senior author of the study. “Our future studies need to show whether BA.2.12.1, BA.4, and BA.5 are not only less efficient at inhibiting antibodies, but also better at infecting lung cells. In this case, it should be noted that the increase in hospitalization has not previously been observed in South Africa, where BA.4 and BA.5 were first detected as a result, “he led the study in collaboration with Markus Hoffmann. Stefan Pöhlmann commented.

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Journal reference:

Arora, P. , et al. (2022) Enhanced neutralization resistance of the new Omicron subvariants BA.2.12.1, BA.4, and BA.5. Lancet infection. doi.org/10.1016/S1473-3099 (22) 00242-4..

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