Strongly inhibit a large number of variants of the new coronavirus! Today's "Nature" highlights the extensive protection of new antibodies

▎The content team editor of WuXi AppTec today accelerated the publication of an important paper in the journal Nature-a research team led by a number of Chinese scientists designed a new IgM antibody therapy, which is more neutralizing than traditional IgG antibody therapy 240 times! It can also bring a powerful neutralizing ability to the multiple variants of new coronaviruses that have appeared all over the world.

The researchers pointed out in the paper that almost all antibodies currently used to neutralize the new coronavirus are IgG.

Such antibodies are difficult to effectively enter the mucosal tissues, so after intravenous infusion, the lung concentration is 200 to 500 times lower than the serum concentration.

In order for this type of antibody therapy to work, we have to use very high doses.

Even so, their antiviral effects still cannot be fully displayed.

In addition, the emerging new variants of new coronaviruses are gradually becoming resistant to these IgG therapies.
For this reason, we need to develop new therapies to meet these challenges.

In addition to IgG, there are many different types of antibodies, among which IgM and IgA1 are antibodies that can fight pathogens in the first line of mucosal tissue.

Normally, IgM forms pentamers, while IgA1 can form dimers.

Multivalent antibodies are not only expected to have a stronger neutralizing ability to the new coronavirus, but also to better promote the transcellular transport in the mucosa, allowing these macromolecules to pass through the cell interior.

In addition, these two antibodies can also be administered through the respiratory tract.

These high-quality properties make IgM and IgA1 a potential new treatment option.

▲ Schematic diagram of the structure of IgG, IgA1 and IgM antibodies (picture source: Reference [1]) In this paper, the researchers used six monoclonal antibodies that can recognize different epitopes of the new coronavirus receptor binding domain (RBD).
Human-derived IgM and IgA1 therapies were designed.

Preliminary results indicate that they can indeed bind to RBD more strongly than IgG therapy.

Among them, an IgM antibody called IgM CoV2-14 (abbreviated as IgM-14) showed the strongest virus inhibitory power and was therefore used for subsequent development.

First, the team confirmed that IgM-14 does have a stronger inhibitory ability.

Compared with the IgG antibody against the same epitope, it can more strongly inhibit the binding of RBD to the ACE2 receptor.

Subsequently, the researchers evaluated the neutralizing ability of IgM-14 to different variants of the new coronavirus.

The study found that whether it is B.
1.
1.
7 (discovered in the UK), P.
1 (discovered in Brazil), or B.
1.
351 (discovered in South Africa) variant viruses, IgM-14 has demonstrated a strong neutralizing ability.

▲A nasal administration allows IgM therapy to be enriched in the nasal cavity and lungs (picture source: reference [1]).
After that, the scientists evaluated the possibility of IgM-14 delivery through the respiratory tract.

In the mouse model, a single nasal administration can enrich the antibody in the nasal cavity and lungs, but hardly appear in the blood and other organs.

In terms of time, this antibody can last for a long time and can be detected in the nasal cavity after 168 hours.

Finally, the research team used nasal administration to evaluate the actual protective effect of IgM-14 on mice.

The results of these in vivo experiments are consistent with the neutralizing ability of IgM-14 in vitro.

For the three variants of new coronaviruses mentioned above, IgM-14 can greatly reduce the amount of virus.

▲For the variant new coronavirus, IgM-14 (red) can also show a better neutralizing effect (picture source: reference [1]) Taken together, the study shows that the designed IgM can become a potential neutralizing therapy , To protect a wide range of variants of the new coronavirus.

Taking into account its good pharmacokinetic properties and safety, IgM antibodies administered through the nasal cavity are not only expected to provide a new weapon against the new crown, but also are expected to become a potential therapy for other respiratory viral infectious diseases.

At present, IGM Biosciences is carrying out follow-up development of this drug and is expected to enter clinical trials in the third quarter of this year.

We also look forward to seeing good follow-up results.

Reference: [1] Ku, Z.
, Xie, X.
, Hinton, PR et al.
Nasal delivery of an IgM offers broad protection from SARS-CoV-2 variants.
Nature (2021).
https://doi.
org /10.
1038/s41586-021-03673-2[2] IGM Biosciences Announces Expansion of IgM Platform into Infectious Diseases, Publication of Preclinical Data in Nature Demonstrating Engineered IgM Antibody Antiviral Activity for the Treatment and Prevention of COVID-19, Retrieved June 3, 2021, from https:// -of-Preclinical-Data-in-Nature-Demonstrating-Engineered-IgM-Antibody-Antiviral-Activity-for-.
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