ABSTRACT
Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) until now imposes a serious burden to health systems globally. Despite worldwide vaccination, social distancing and wearing masks, the spread of the virus is still ongoing. One of the mechanisms how neutralizing antibodies (NAbs) block virus entry into cells encompasses interaction inhibition between the cell surface receptor angiotensin-converting enzyme 2 (ACE2) and the spike (S) protein of SARS-CoV-2. SARS-CoV-2 specific NAb development can be induced in the blood of cattle. Pregnant cows produce NAbs upon immunization, and antibodies move into the colostrum just before calving. Here we immunized cows with SARS-CoV-2 S1 receptor binding domain (RBD) protein in proper adjuvant solutions, followed by one boost with SARS-CoV-2 trimeric S protein, and purified immunoglobulins from colostrum. We demonstrate that this preparation indeed blocks interaction between the trimeric S protein and ACE2 in different in vitro assays. Moreover, we describe the formulation of purified immunoglobulin preparation into a nasal spray. When administered to human subjects, the formulation persists on the nasal mucosa for at least 4 hours as determined by a clinical study. Therefore, we are presenting a solution that shows great potential to serve as a prophylactic agent against SARS-CoV-2 infection as an additional measure to vaccination and wearing masks. Moreover, our technology allows for a rapid and versatile adaption for preparing prophylactic treatments against other diseases by using the defined characteristics of antibody movement into the colostrum. SignificanceSARS-CoV-2 infections continue to be a high-risk factor for mankind. Antibodies with the potential to neutralize the virus and thus its entry into the host cell have been shown to impose a potent measure against the infection. Human derived neutralizing antibodies are therapeutics and thus fall under the legislation of drugs. However, an alternative could be the purification of efficient neutralizing antibodies from other species. Here, we present immunization of pregnant cows with spike protein of SARS-CoV-2 which results in high quantities of colostrum immunoglobulins that can be easily harvested and safely purified within a remarkably short time. The colostrum immunoglobulin preparation has a great potential to serve in formulations that can be used as prophylactic agent against SARS-CoV-2 infection.
