Bovine-derived polyclonal antibodies exhibit high efficacy in neutralizing SARS-CoV-2 variants

A team of scientists in Estonia has recently evaluated the therapeutic/prophylactic efficacy of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polyclonal antibodies derived from the colostrum of immunized cows. The antibodies exhibit high efficiency in inhibiting the interaction between SARS-CoV-2 spike protein and human angiotensin-converting enzyme 2 (ACE2). Furthermore, the scientists have prepared a nasal spray formulation with colostrum antibodies that persists in the human nasal mucosa for at least 4 hours.

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources

A preprint version of the study is available on the medRxiv* server, while the article undergoes peer review.

Background

As of June 10, 2021, globally, there have been 173 million confirmed cases of coronavirus disease 2019 (COVID-19), including 3.7 million deaths, registered to the World Health Organization (WHO). Despite the strict implementation of control measures and rapid vaccination programs, the number of COVID-19 cases is continuously expanding worldwide. This could potentially be due to the emergence of novel viral variants with multiple spike mutations, which are able to escape host immunity developed in response to natural infection or vaccination.

In both clinical trials and real-world situations, neutralizing monoclonal antibodies have shown good therapeutic and prophylactic efficiencies against SARS-CoV-2 infection. In the majority of the cases, neutralizing antibodies are developed against the viral spike protein, which prevents SARS-CoV-2 host cell entry by binding to the spike protein, and thus, inhibiting the spike – ACE2 attachment. Thus, passive immunization with neutralizing antibodies is particularly helpful in preventing SARS-CoV-2 infection at the early stage.

In the current study, the scientists have derived anti-SARS-CoV-2 polyclonal antibodies from the colostrum of immunized cows, which show high efficiency in blocking viral infection. They have also prepared a nasal spray formulation containing colostrum-derived antibodies and determined its bioavailability in the human nasal mucosa.

Study design

To induce antibody production, the scientists immunized 8 cows with SARS-CoV-2 spike receptor-binding domain (RBD) protein in proper adjuvant solutions twice at an interval of 3 weeks. Afterward, they administered the cows with one booster dose of SARS-CoV-2 trimeric spike protein two weeks after the 2nd vaccine dose.

In mammals, antibodies developed against exogenous pathogens are naturally accumulated in the colostrum so that the protective immunity can be transferred to newborns through colostrum. Given this natural phenomenon, the scientists collected colostrum from each immunized cow as an enriched source of anti-SARS-CoV-2 polyclonal antibodies.

To obtain whey (the watery part of the milk), they removed lipids from the colostrum. Afterward, they pooled all whey fractions and processed them through different filtration and fractional precipitation steps to obtain the purified preparation of anti-SARS-CoV-2 antibodies.

Important observations

Competitive enzyme-linked immunosorbent assay was carried out to determine the ability of colostrum antibody preparation in preventing spike – ACE2 binding. The findings revealed that the antibody preparation is highly efficient in preventing the trimeric spike protein of the original SARS-CoV-2 strain and its variants from binding human ACE2. Although a comparable inhibitory effect was observed against the original strain and the B.1.1.7 variant, the antibody preparation exhibited relatively less potency in blocking the B.1.351 and P.1 variants.

Furthermore, the pseudoviral neutralization assay findings revealed that the antibody preparation effectively blocks the host cell entry of pseudoviruses carrying spike protein of original SARS-CoV-2 strain or the B.1.1.7, B.1.351, P.1, B.1.617.1 or B.1.617.2 variants. However, compared to other tested variants, B.1.351 and P.1 exhibited higher resistance to antibody preparation-mediated neutralization.

Importantly, the antibody preparation exhibited high potency in inhibiting the cytopathic effects induced by the authentic SARS-CoV-2 even at low nanomolar concentrations.

Nasal spray formulation containing colostrum antibodies

Since SARS-CoV-2 primarily attacks the upper respiratory tract, the scientists thought of preparing a nasal spray formulation with colostrum antibodies. They also determined how long the preparation remains active at the site of delivery.

For this purpose, they enrolled 16 healthy volunteers. The antibody preparation was administered at two different concentrations via nasal spray twice into each nostril. The nasal samples were collected 1 and 4 hours after administration of the antibody preparation to measure antibody levels in the nasal cavity.

The findings revealed that high amounts of anti-SARS-CoV-2 antibodies could be detected in the nasal mucosa even after 4 hours of spraying.

Study significance

The study describes a novel process of inducing anti-SARS-CoV-2 polyclonal antibodies in the colostrum of cows immunized with viral spike RBD. The antibody preparation exhibits high neutralization potency against SARS-CoV-2 and its variants, including B.1.1.7, B.1.351, P.1, B.1.617.1 and B.1.617.2.

The bioavailability studies reveal that the colostrum antibody preparation administered via nasal spray remains detectable in the nasal mucosa for at least 4 hours.

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources

Journal references:

Article Revisions

  • Apr 10 2023 - The preprint preliminary research paper that this article was based upon was accepted for publication in a peer-reviewed Scientific Journal. This article was edited accordingly to include a link to the final peer-reviewed paper, now shown in the sources section.
Dr. Sanchari Sinha Dutta

Written by

Dr. Sanchari Sinha Dutta

Dr. Sanchari Sinha Dutta is a science communicator who believes in spreading the power of science in every corner of the world. She has a Bachelor of Science (B.Sc.) degree and a Master's of Science (M.Sc.) in biology and human physiology. Following her Master's degree, Sanchari went on to study a Ph.D. in human physiology. She has authored more than 10 original research articles, all of which have been published in world renowned international journals.

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