By Marija Djekic Ivankovic

Due to the ongoing pace of the COVID-19 pandemic, alongside the available vaccines, there is increased interest in complementary therapeutics. Several anti-SARS-CoV-2 antibody-based therapies have been approved for emergency-use, but viral resistance represents a major challenge in light of emerging variants. According to a recent study published in Nature, a new engineered IgM antibody that can be administered as a spray through the nose was more effective than previous IgG-based therapeutics at neutralizing the SARS-CoV-2 virus in animal models across a broad range of emerging variants, including Alpha (originally detected in the U.K.), Beta (originally detected in South Africa), and Gamma (originally detected in Brazil) variants of concern.


Key points:

    • Researchers developed a novel engineered IgM antibody spray that was shown to be effective against SARS-COV-2 and some variants of concern.
    • This therapy can be effectively delivered through the nose to confer protection against SARS-CoV-2 infection in animals (i.e., this hasn’t been tested in humans yet).
    • This novel nasal spray could be used as a therapy if someone developed an infection, to reduce viral transmission and block the infection by neutralization.
    • It could also potentially be used to prevent SARS-CoV-2 infection development if someone was exposed to COVID.
    • The key to this therapeutic advance is determining the correct epitopes An epitope is the part of an antigen molecule to which an antibody attaches itself. to use to produce the antibodies that will be engineered.


IgM antibodies are known as nature’s first line of defense against pathogens such as viruses. In the respiratory mucosa, IgM antibodies play a key role in clearing SARS-CoV-2 infection and reducing viral transmission. Spraying this novel engineered IgM antibody (IgM-14) in the nose has been shown to reduce resistance and simplify treatments for SARS-CoV-2.

The researchers also demonstrated that IgM-14 administered as a nasal spray was >230-fold more potent than a commonly used IgG-based therapeutic (IgG-14) in neutralizing SARS-CoV-2 viruses in an infected mouse model. One single intranasal dose of 0.044 and 0.4 mg/kg IgM-14 provided efficacy against SARS-CoV-2 in mice. Finally, IgM-14, but not IgG-14, also has potent therapeutic protection against the Alpha, Beta, and Gamma variants of concern.

In summary, the novel nasal spray with an engineered IgM antibody is a promising treatment with potent neutralization against SARS-CoV-2, broad coverage against variants of concern, desirable pharmacokinetics, and safety profiles that provides effective respiratory protection. This can also be envisioned as a new therapeutic platform for tackling other respiratory viral diseases.


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. Nasal delivery of an IgM offers broad protection from SARS-CoV-2 variants. Nature. 2021 Jun 3. doi: 10.1038/s41586-021-03673-2.


  • Pop up: An epitope is the part of an antigen molecule to which an antibody attaches itself.