Bovine colostrum-derived antibodies against SARS-CoV-2 show great potential to serve as prophylactic agents

Kangro, Kadri; Kurašin, Mihhail; Gildemann, Kiira; Sankovski, Eve; Žusinaite, Eva; Lello, Laura Sandra; Pert, Raini; Kavak, Ants; Poikalainen, V.; Lepasalu, L.; Kuusk, Marilin; Pau, Robin; Piiskop, Sander; Rom, Siimu; Oltjer, Ruth; Tiirik, Kairi; Kogermann, Karin; Plaas, Mario; Tiirats, Toomas; Aasmäe, Birgit; Plaas, Mihkel; Mumm, Karl; Krinka, Dagni; Talpsep, Ene; Kadaja, Meelis; Gerhold, Joachim M.; Planken, Anu; Tover, Andres; Merits, Andres; Männik, Andres; Ustav, Mart

doi:10.1371/journal.pone.0268806

Cited by 14 publications

(10 citation statements)

References 42 publications

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“…Pregnant large farm mammals produce antibodies upon immunization, and the antibodies move into the colostrum immediately before delivery of offspring. Such polyclonal nAbs showed potential to serve as prophylactic agents against influenza and SARS-CoV-2 infection in vivo [ 15 , 16 ].…”

Section: Antiviral Agents and Therapiesmentioning

confidence: 99%

Seven classes of antiviral agents

Ianevski

Ahmad

Anunnitipat

et al. 2022

Cell. Mol. Life Sci.

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The viral epidemics and pandemics have stimulated the development of known and the discovery of novel antiviral agents. About a hundred mono- and combination antiviral drugs have been already approved, whereas thousands are in development. Here, we briefly reviewed 7 classes of antiviral agents: neutralizing antibodies, neutralizing recombinant soluble human receptors, antiviral CRISPR/Cas systems, interferons, antiviral peptides, antiviral nucleic acid polymers, and antiviral small molecules. Interferons and some small molecules alone or in combinations possess broad-spectrum antiviral activity, which could be beneficial for treatment of emerging and re-emerging viral infections.

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Section: Antiviral Agents and Therapiesmentioning

confidence: 99%

Seven classes of antiviral agents

Ianevski

Ahmad

Anunnitipat

et al. 2022

Cell. Mol. Life Sci.

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“…containing anti-SARS-CoV-2 antibodies 27,28 . Any nasal products other than the study products were prohibited during the study period.…”

Section: Safety Evaluationmentioning

confidence: 99%

“…Participants sprayed 2 puffs (100 µl per puff) of the study products into each nostril thrice daily at 8 am, 2 pm, and 8 pm for 7 days. The volume and frequency of the study product application were based on reports of other nasal spray products containing anti-SARS-CoV-2 antibodies 27,28 . Any nasal products other than the study products were prohibited during the study period.…”

Section: Enzyme-linked Immunosorbent Assay (Elisa)mentioning

confidence: 99%

A randomized, placebo-controlled trial of a nasal spray solution containing broadly potent neutralizing antibodies against SARS-CoV-2 variants in healthy volunteers

Imsuwansri

Jongthitinon

Pojdoung

et al. 2022

Preprint

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Successful COVID-19 prevention requires additional measures beyond vaccination, social distancing, and masking. A nasal spray solution containing human IgG1 antibodies against SARS-CoV-2 (COVITRAP™) was developed to strengthen other COVID-19 preventive arsenals. Here, we evaluated its pseudovirus neutralization potencies, preclinical and clinical safety profiles, and intranasal SARS-CoV-2 inhibitory effects in healthy volunteers (NCT05358873). COVITRAP™ exhibited broadly potent neutralizing activities against SARS-CoV-2 with PVNT50 values ranging from 0.0035 to 3.1997 μg/ml for the following variants of concern (ranked from lowest to highest): Alpha, Beta, Gamma, Ancestral, Delta, Omicron BA.1, Omicron BA.2, Omicron BA.4/5, and Omicron BA.2.75. It demonstrated satisfactory preclinical safety profiles based on evaluations of in vitro cytotoxicity, skin sensitization, intracutaneous reactivity, and systemic toxicity. Its intranasal administration in rats did not yield any detected circulatory levels of the human IgG1 anti-SARS-CoV-2 antibodies at any time point during the 120 hours of follow-up. A double-blind, randomized, placebo-controlled trial (RCT) was conducted on 36 healthy volunteers who received either COVITRAP™ or a normal saline nasal spray at a 3:1 ratio. Safety of the thrice-daily intranasal administration for 7 days was assessed using nasal sinuscopy, adverse event recording, and self-reporting questionnaires. COVITRAP™ was well tolerated, with no significant adverse effects in healthy volunteers for the entire 14 days of the study. The intranasal SARS-CoV-2 inhibitory effects of COVITRAP™ were evaluated in nasal fluids taken from volunteers pre- and post-administration using a SARS-CoV-2 surrogate virus neutralization test. SARS-CoV-2 inhibitory effects in nasal fluids collected immediately or six hours after COVITRAP™ application were significantly increased from baseline for all three variants tested, including Ancestral, Delta, and Omicron BA.2. In conclusion, COVITRAP™ was safe for intranasal use in humans to provide SARS-CoV-2 inhibitory effects in nasal fluids that lasted at least six hours. Therefore, COVITRAP™ can be considered an integral instrument for COVID-19 prevention.

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“…Polyclonal antibodies are easier to produce at low cost. However, many natural sources for the production of polyclonal antibodies have not been fully explored or understood [ 6 ]. Chicken egg yolk immunoglobulins (IgYs) possess therapeutic potential, with many advantages [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Antiviral Immunoglobulins of Chicken Egg Yolk for Potential Prevention of SARS-CoV-2 Infection

Evensen

Sanson

Hildonen

et al. 2022

Viruses

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Background: Some viruses cause outbreaks, which require immediate attention. Neutralizing antibodies could be developed for viral outbreak management. However, the development of monoclonal antibodies is often long, laborious, and unprofitable. Here, we report the development of chicken polyclonal neutralizing antibodies against SARS-CoV-2 infection. Methods: Layers were immunized twice with 14-day intervals using the purified receptor-binding domain (RBD) of the S protein of SARS-CoV-2/Wuhan or SARS-CoV-2/Omicron. Eggs were harvested 14 days after the second immunization. Polyclonal IgY antibodies were extracted. Binding of anti-RBD IgYs was analyzed by immunoblot and indirect ELISA. Furthermore, the neutralization capacity of anti-RBD IgYs was measured in Vero-E6 cells infected with SARS-CoV-2-mCherry/Wuhan and SARS-CoV-2/Omicron using fluorescence and/or cell viability assays. In addition, the effect of IgYs on the expression of SARS-CoV-2 and host cytokine genes in the lungs of Syrian Golden hamsters was examined using qRT-PCR. Results: Anti-RBD IgYs efficiently bound viral RBDs in situ, neutralized the virus variants in vitro, and lowered viral RNA amplification, with minimal alteration of virus-mediated immune gene expression in vivo. Conclusions: Altogether, our results indicate that chicken polyclonal IgYs can be attractive targets for further pre-clinical and clinical development for the rapid management of outbreaks of emerging and re-emerging viruses.

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Bovine colostrum-derived antibodies against SARS-CoV-2 show great potential to serve as prophylactic agents

Cited by 14 publications

References 42 publications

Seven classes of antiviral agents

Seven classes of antiviral agents

A randomized, placebo-controlled trial of a nasal spray solution containing broadly potent neutralizing antibodies against SARS-CoV-2 variants in healthy volunteers

Antiviral Immunoglobulins of Chicken Egg Yolk for Potential Prevention of SARS-CoV-2 Infection

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