Cross-immunity: Can cow's milk help fight COVID-19?

SARS-CoV-2 shares many characteristics with other coronaviruses in the same family, to the point that cross-immunity may be possible. Researchers want to evaluate the therapeutic potential of antibodies directed against a bovine coronavirus for treating the pandemic virus. Easily produced at low cost, these antibodies could be consumed in the form of milk from immunized cows. Two years into the COVID-19 pandemic, treatment options for this disease remain limited. As with many viral infections, there is still no effective specific treatment against the SARS-CoV-2 coronavirus. To limit severe cases, it is becoming urgent to find immune and pharmacological mechanisms and strategies to control the disease. Vaccines that build preventive immune defenses have proven effective, and certain antibodies are already being used to neutralize the virus. Researchers are now proposing to harness cross-immunity transmitted through milk from immunized cows. SARS-CoV-2 is a coronavirus, but it is far from being the only one. Many others infect the animal kingdom, notably BCoV, a bovine coronavirus that causes diarrhea and gastroenteritis in young, unimmunized calves, with possible respiratory complications. Due to their economic, medical, and epidemiological significance, various commercial vaccines against BCoV (including live and inactivated vaccines) are currently available and have demonstrated very good protective efficacy. It would therefore be relatively easy and inexpensive to obtain immunized milk quickly and in large quantities. Indeed, bovine immunoglobulin G is functionally active throughout the gastrointestinal tract and can prevent infections of the digestive and respiratory tracts in humans. SARS-CoV-2 and BCoV are phylogenetically very closely related β-coronaviruses that share common characteristics. Structurally, BCoV is enveloped by five structural proteins, four of which are identical to those of SARS-CoV-2: the spike glycoprotein (S), the envelope protein (E), the membrane protein (M), the nucleocapsid protein (N), and the hemagglutinin-esterase (HE). Among these shared proteins is the spike protein (S). It is this same protein—which is widely exposed on the viral surface—that triggers an immune response against the virus and constitutes an immunodominant structure against which the vaccines developed to date are directed. Various studies show that this similarity between the viruses gives rise to cross-immunity, as they retain these shared epitopes. The dynamics of antibody production following natural infection appear to be very similar between BCoV and SARS-CoV-2. In fact, several classes of antibodies (IgA, IgM, IgG) are produced and directed against the virus’s various structural proteins. The presence of specific immunoglobulins in the intestinal lumen would then help control viral shedding. The researchers therefore propose leveraging heterologous passive immunity to BCoV—induced by milk from immunized cows—to deliver an immunostimulatory therapy and thereby control SARS-CoV-2 infection. Whole cow’s milk contains more than 30 g/L of proteins, including nearly 1 g/L of immunoglobulins. These antibodies in bovine milk survive gastric exposure and resist proteolytic digestion in the stomach and intestine. Thus, colostrum confers passive immunity that provides remarkable protection against most infectious animal diseases and has been extensively studied for nearly all coronaviruses of veterinary interest. Antibodies specific to SARS-CoV-2 have also been detected in human colostrum. Logically, cow’s milk immunized against BCoV should activate the intestinal immune system against the virus and, at the same time, induce cross-immunity against SARS-CoV-2 through antigenic recognition of certain highly conserved structures, which are highly conserved, particularly the M and S proteins. Anti-BCoV antibodies present in the milk would lead to total or partial inactivation of SARS-CoV-2, acting somewhat like a vaccine and supporting the specific immune response. The complexity of the cytokine network in humans makes immunomodulation essential for controlling severe cases of COVID-19, and this could be achieved through the presence of specific immunoglobulins in gut-associated lymphoid tissue and in the intestinal lumen. Given these findings, researchers aim to further investigate the efficacy of immunized milk and other immune-boosting compounds (derived from milk, egg yolk, etc.) in controlling the disease in human patients.