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.
Highlights
Respiratory syncytial virus (RSV) infections are a major disease burden in infants and RSV is the second most prevalent cause of death in children, mostly affecting children in low- and middle-income countries [1, 2]
Binding of bovine colostrum IgG (bIgG) was equal to cells infected with both RSV strains, similar to what was observed with Intravenous Immunoglobulin (IVIG) and palivizumab (Figure 1A)
We have demonstrated that bovine IgG binds to two different strains of human RSV, facilitates the activation of RSVspecific T cells, and reduces viral load with RSV in a prophylactic RSV in vivo mouse model
Summary
Respiratory syncytial virus (RSV) infections are a major disease burden in infants and RSV is the second most prevalent cause of death in children, mostly affecting children in low- and middle-income countries [1, 2]. It has been shown that breastfeeding reduces the severity and incidence of RSV infections in children [5]. Four months exclusive breastfeeding reduces the risk on respiratory and gastro-intestinal tract infections [8, 9]. Most children in developed countries fully rely on bovine milk based infant formulas that do not seem to offer a similar level of protection against these pathogens. Palivizumab binds to the post fusion form of the F protein [11]. The F protein undergoes conformational changes after RSV binding facilitating fusion with host cells [11]
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