Nasal delivery of an IgM offers broad protection from SARS-CoV-2 variants

Abstract

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Antibody Attributes that Predict the Neutralization and Effector Function of Polyclonal Responses to SARS-CoV-2

“…Consistent with our experimental results, another study in which IgM was selectively depleted also observed resulting reduction in neutralization activity, but additionally confirmed the activity of the isolated IgM fraction 62,63 . Interestingly, SARS-CoV-2 specific IgM administered intranasally has been shown to be effective in treating novel SARS-CoV-2 variants of concern, including the alpha, beta, and gamma variants in a mouse model 64 . The finding that so much of the neutralizing activity of convalescent plasma against SARS-CoV-2 resides in the IgM fraction raises concern about that gamma globulin preparations may lose much of their antiviral activity as this isotype is removed.…”

Monoclonal antibodies for the treatment of COVID-19 patients: An umbrella to overcome the storm?

“…IgM antibodies are usually the first line in the defence of mucous tissues. IgG-14 administered intranasally in a single dose showed persistently high levels in the nasal cavity of mice, while blood and other tissues had minimal antibody exposure [63] . The intranasal delivery of IgM-14 or other sprayed monoclonal antibodies could allow highly effective protection; so it has to be considered as a useful resource in alternative to intravenous administration of other monoclonal antibodies already approved for clinical use.…”

“…Last but not least, a study recently published [63] evaluated intranasal administration in mice of an IgM engineered antibody, IgM-14. So far most neutralizing monoclonal antibodies were IgG1 isotype and were administered intravenously; nevertheless, IgG antibodies have low mucosal penetration.…”

“…The intranasal delivery of IgM-14 or other sprayed monoclonal antibodies could allow highly effective protection; so it has to be considered as a useful resource in alternative to intravenous administration of other monoclonal antibodies already approved for clinical use. In addition, IgM-14 has shown broad coverage of P1 (Gamma) and B.1.351 (Beta) mouse-adapted variants, with higher efficacy than the intranasally administered corresponding IgG-14 [63] .…”

Can the Nasal Cavity Help Tackle COVID-19?

“…In a recent study, Ku et al [90] reported that a COVID-19 antibody treatment they engineered has proved to be very effective at neutralizing more than 20 variants of SARS-coV-2 in mice. The new antibody-based therapy for COVID-19 is based on the development of an immunoglobulin M (IgM) neutralizing antibody (IgM-14) as an approach to overcome the resistance encountered by immunoglobulin G (IgG)-based therapeutics.…”