Bovine IgG Prevents Experimental Infection With RSV and Facilitates Human T Cell Responses to RSV

Abstract

Respiratory syncytial virus (RSV) infections represent a major burden of disease in infants and are the second most prevalent cause of death worldwide. Human milk immunoglobulins provide protection against RSV. However, many infants depend on processed bovine milk-based nutrition, which lacks intact immunoglobulins. We investigated the potential of bovine antibodies to neutralize human RSV and facilitate-cell immune activation. We show cow's milk IgG (bIgG) and Intravenous Immunoglobulin (IVIG) have a similar RSV neutralization capacity, even though bIgG has a lower pre-F to post-F binding ratio compared to human IVIG, with the majority of bIgG binding to pre-F. RSV is better neutralized with human IVIG. Consequently, we enriched RSV specific T cells by culturing human PBMC with a mixture of RSV peptides, and used these T cells to study the effect of bIgG and IVIG on the activation of pre-F-pecific T cells. bIgG facilitated in vitro T cell activation in a similar manner as IVIG. Moreover, bIgG was able to mediate T cell activation and internalization of pathogens, which are prerequisites for inducing an adaptive viral response. Using in vivo mouse experiments, we showed that bIgG is able to bind the murine activating IgG Fc Receptors (FcγR), but not the inhibiting FcγRII. Intranasal administration of the monoclonal antibody palivizumab, but also of bIgG and IVIG prevented RSV infection in mice. The concentration of bIgG needed to prevent infection was ∼5-fold higher compared to IVIG. In conclusion, the data presented here indicate that functionally active bIgG facilitates adaptive antiviral T cell responses and prevents RSV infection in vitro and in vivo.

Bovine Colostrum: Its Constituents and Uses

“…Examples include findings that BC supplementation reduced the number of flu-like episodes [ 141 ]. BC supplementation has also been reported to be beneficial in reducing the number of upper respiratory tract infections (URTIs) and diarrhoeal episodes in children [ 142 , 143 ], and BC IgG has been shown to bind and neutralise human respiratory syncytial virus [ 144 ]. Similarly, athletes undergoing training are known to have increased risk of URTI symptoms, and metanalyses of published trials reported a significant positive effect of BC supplementation [ 145 ].…”

Insights into the Research Trends on Bovine Colostrum: Beneficial Health Perspectives with Special Reference to Manufacturing of Functional Foods and Feed Supplements

“…Human respiratory syncytial virus (RSV) is a common, contagious virus that causes respiratory infections, namely bronchiolitis, common cold, and serious illness for infants and elderly persons. To study the preventive action of isolated IgG from bovine colostrum in response to RSV, an animal trial was carried out by Nederend et al [ 100 ]. BC was collected within 5 days after parturition, and IgG was isolated from whey by using affinity purification and evaluated for a binding property with culture HEp-2 cells infected with two strains of RSV in a mouse model (in vitro).…”

The contribution of bovines to human health against viral infections

“…bIgG promotes adaptive antiviral T cell responses and protects against RSV infection in vitro and in vivo. Therefore, purified bIgG can be added to infant formulas to pass some of the beneficial effects of raw bovine milk to microbiologically stable infant formulas (Nederend et al 2020), which not undergo heat treatment to avoid reducing the protective effect of bovine milk (Mainer et al 1997;Loss et al 2015). Bovine lactoferrin (BL), protein found in cow milk, indirectly reduces human norovirus infection via inducing the innate interferon responses (Oda et al 2021) and has a therapeutic potential against SARS-CoV-2 (Batista da Silva Galdino et al 2021).…”