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Could a Nasal Spray of Designer Antibodies Help to Beat COVID-19?

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Woman inhaling yellow particles on left. On right, coronavirus with yellow IgM antibodies covering some of the spikes of a cornavirus.

There are now several monoclonal antibodies, identical copies of a therapeutic antibody produced in large numbers, that are authorized for the treatment of COVID-19. But in the ongoing effort to beat this terrible pandemic, there’s plenty of room for continued improvements in treating infections with SARS-CoV-2, the virus that causes COVID-19.

With this in mind, I’m pleased to share progress in the development of a specially engineered therapeutic antibody that could be delivered through a nasal spray. Preclinical studies also suggest it may work even better than existing antibody treatments to fight COVID-19, especially now that new SARS-CoV-2 “variants of concern” have become increasingly prevalent.

These findings come from Zhiqiang An, The University of Texas Health Science Center at Houston, and Pei-Yong Shi, The University of Texas Medical Branch at Galveston, and their colleagues. The NIH-supported team recognized that the monoclonal antibodies currently in use all require time-consuming, intravenous infusion at high doses, which has limited their use. Furthermore, because they are delivered through the bloodstream, they aren’t able to reach directly the primary sites of viral infection in the nasal passages and lungs. With the emergence of new SARS-CoV-2 variants, there’s also growing evidence that some of those therapeutic antibodies are becoming less effective in targeting the virus.

Antibodies come in different types. Immunoglobulin G (IgG) antibodies, for example, are most prevalent in the blood and have the potential to confer sustained immunity. Immunoglobulin A (IgA) antibodies are found in tears, mucus, and other bodily secretions where they protect the body’s moist, inner linings, or mucosal surfaces, of the respiratory and gastrointestinal tracts. Immunoglobulin M (IgM) antibodies are also important for protecting mucosal surfaces and are produced first when fighting an infection.

Though IgA and IgM antibodies differ structurally, both can be administered in an inhaled mist. However, monoclonal antibodies now used to treat COVID-19 are of the IgG type, which must be IV infused.

In the new study, the researchers stitched IgG fragments known for their ability to target SARS-CoV-2 together with those rapidly responding IgM antibodies. They found that this engineered IgM antibody, which they call IgM-14, is more than 230 times better than the IgG antibody that they started with in neutralizing SARS-CoV-2.

Importantly, IgM-14 also does a good job of neutralizing SARS-CoV-2 variants of concern. These include the B.1.1.7 “U.K.” variant (now also called Alpha), the P.1 “Brazilian” variant (called Gamma), and the B.1.351 “South African” variant (called Beta). It also works against 21 other variants carrying alterations in the receptor binding domain (RBD) of the virus’ all-important spike protein. This protein, which allows SARS-CoV-2 to infect human cells, is a prime target for antibodies. Many of these alterations are expected to make the virus more resistant to monoclonal IgG antibodies that are now authorized by the FDA for emergency use.

But would it work to protect against coronavirus infection in a living animal? To find out, the researchers tried it in mice. They squirted a single dose of the IgM-14 antibody into the noses of mice either six hours before exposure to SARS-CoV-2 or six hours after infection with either the P.1 or B.1.351 variants.

In all cases, the antibody delivered in this way worked two days later to reduce dramatically the amount of SARS-CoV-2 in the lungs. That’s important because the amount of virus in the respiratory tracts of infected people is closely linked to severe illness and death due to COVID-19. If the new therapeutic antibody is proven safe and effective in people, it suggests it could become an important tool for reducing the severity of COVID-19, or perhaps even preventing infection altogether.

The researchers already have licensed this new antibody to a biotechnology partner called IGM Biosciences, Mountain View, CA, for further development and future testing in a clinical trial. If all goes well, the hope is that we’ll have a safe and effective nasal spray to serve as an extra line of defense in the fight against COVID-19.

Reference:

[1] Nasal delivery of an IgM offers broad protection from SARS-CoV-2 variants. Ku Z, Xie X, Hinton PR, Liu X, Ye X, Muruato AE, Ng DC, Biswas S, Zou J, Liu Y, Pandya D, Menachery VD, Rahman S, Cao YA, Deng H, Xiong W, Carlin KB, Liu J, Su H, Haanes EJ, Keyt BA, Zhang N, Carroll SF, Shi PY, An Z. Nature. 2021 Jun 3.

Links:

COVID-19 Research (NIH)

Zhiqiang An (The University of Texas Health Science Center at Houston)

Pei-Yong Shi (The University of Texas Medical Branch at Galveston)

IGM Biosciences (Mountain View, CA)

NIH Support: National Institute of Allergy and Infectious Diseases; National Center for Advancing Translational Sciences; National Cancer Institute

10 Comments

  • Ann O'Malley says:

    Very encouraging! TG for the scientists.

  • Pat Chieffo says:

    Nasal spray! Very promising! I hope the human trials are not too far in the future!

  • Duke van Kalken says:

    An alternate treatment could be to mist a low ppm Ultra-Lyte (anolyte) solution in the nasal cavity.

  • Nadja says:

    I hope the nasal spray comes soon.

  • Gary b says:

    What about rlf100 zysami? Waiting on approval.

  • Fraser says:

    Less risky than causing auto-immunity against ACE2 or neuropilin agonists and antagonists.

  • BSanon-Prud'homme says:

    Nasal spray sounds very promising.

  • S Kautish says:

    This will be really helpful as I decided not to take vaccination due to its unknown side effects but still afraid of it.

  • DR. SAUMYA PANDEY, PH.D. says:

    Nasal spray for Covid-19 prevention developed by a leading biotechnology corporate in CA, USA is indeed an innovative, patient-friendly, low-cost immunotherapeutically safe intervention/strategy for at-risk ethnically disparate population-subsets.
    Congratulations to my contemporary American immunology-infectious diseases-immunopharmacology scientific experts based in USA for a brilliant scientific innovation in the complex Covid-19 global pandemic!

  • V.Chidambaranathan says:

    I am a organic stereochemist.Carried out studies on steroscopic binding between active sites in enzymes and non self drug molecules to assess their toxicity quantitatively.
    Sytereosopic binding between the atoms in the proteins of pathogens and atoms in the proteins of immune system decides whether pathogens would be neutralized or immuno proteins would be compromised.
    From the chemist point of view,proximity /contact leads to binding.This may take place either in the nasal cavity or in the alveoli.
    If masks are coated with monoclonal bodies again the same binding will take placewhich prevents the entry of pathogens.
    My interest is to know whether any study of vaccine coated masks have been carried out.
    Thanks!

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