Specificity and Effector Functions of Human RSV-Specific IgG from Bovine Milk.
BACKGROUND
Respiratory syncytial virus (RSV) infection is the second most important cause of death in the first year of life, and early RSV infections are associated with the development of asthma. Breastfeeding and serum IgG have been shown to protect against RSV infection. Yet, many infants depend on bovine milk-based nutrition, which at present lacks intact immunoglobulins.


OBJECTIVE
To investigate whether IgG purified from bovine milk (bIgG) can modulate immune responses against human RSV.


METHODS
ELISAs were performed to analyse binding of bIgG to human respiratory pathogens. bIgG or hRSV was coated to plates to assess dose-dependent binding of bIgG to human Fcγ receptors (FcγR) or bIgG-mediated binding of myeloid cells to hRSV respectively. S. Epidermidis and RSV were used to test bIgG-mediated binding and internalisation of pathogens by myeloid cells. Finally, the ability of bIgG to neutralise infection of HEp2 cells by hRSV was evaluated.


RESULTS
bIgG recognised human RSV, influenza haemagglutinin and Haemophilus influenza. bIgG bound to FcγRII on neutrophils, monocytes and macrophages, but not to FcγRI and FcγRIII, and could bind simultaneously to hRSV and human FcγRII on neutrophils. In addition, human neutrophils and dendritic cells internalised pathogens that were opsonised with bIgG. Finally, bIgG could prevent infection of HEp2 cells by hRSV.


CONCLUSIONS
The data presented here show that bIgG binds to hRSV and other human respiratory pathogens and induces effector functions through binding to human FcγRII on phagocytes. Thus bovine IgG may contribute to immune protection against RSV.
Laboratory of Translational Immunology, Immunotherapy group, UMC Utrecht, Utrecht, The Netherlands; Cell Biology and Immunology, Wageningen University, Wageningen, The Netherlands.
Gerco
G
den Hartog
Laboratory of Translational Immunology, Immunotherapy group, UMC Utrecht, Utrecht, The Netherlands.
Shamir
S
Jacobino
Laboratory of Translational Immunology, Immunotherapy group, UMC Utrecht, Utrecht, The Netherlands; Department of Pediatrics, UMC Utrecht, Utrecht, The Netherlands.
Louis
L
Bont
Bioceros, Utrecht, The Netherlands.
Linda
L
Cox
FrieslandCampina, Amersfoort, The Netherlands.
Laurien H
LH
Ulfman
Laboratory of Translational Immunology, Immunotherapy group, UMC Utrecht, Utrecht, The Netherlands.
Jeanette H W
JH
Leusen
Cell Biology and Immunology, Wageningen University, Wageningen, The Netherlands; FrieslandCampina, Amersfoort, The Netherlands.
R J Joost
RJ
van Neerven
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology / Q000302:isolation & purification*; D002417:Cattle; D006193:Haemophilus influenzae / Q000276:immunology; D056945:Hep G2 Cells; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000302:isolation & purification*; D008892:Milk / Q000276:immunology*; D022423:Myeloid Cells / Q000276:immunology; D017452:Receptors, IgG / Q000378:metabolism*; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology*; D013045:Species Specificity
D000914:Antibodies, Viral; D007074:Immunoglobulin G; D017452:Receptors, IgG