title: Intranasal administration of antibody-bound respiratory syncytial virus particles efficiently primes virus-specific immune responses in mice.
abstract: Infants are protected from a severe respiratory syncytial virus (RSV) infection in the first months of life by maternal antibodies or by prophylactically administered neutralizing antibodies. Efforts are under way to produce RSV-specific antibodies with increased neutralizing capacity compared to the currently licensed palivizumab. While clearly beneficial during primary infections, preexisting antibodies might affect the onset of adaptive immune responses and the ability to resist subsequent RSV infections. Therefore, we addressed the question of how virus neutralizing antibodies influence the priming of subsequent adaptive immune responses. To test a possible role of the neonatal Fc receptor (FcRn) in this process, we compared the responses in C57BL/6 wild-type (WT) and FcRn(-/-) mice. We observed substantial virus-specific T-cell priming and B-cell responses in mice primed with RSV IgG immune complexes resulting in predominantly Th1-type CD4(+) T-cell and IgG2c antibody responses upon live-virus challenge. RSV-specific CD8(+) T cells were primed as well. Activation of these adaptive immune responses was independent of FcRn. Thus, neutralizing antibodies that localize to the airways and prevent infection-related routes of antigen processing can still facilitate antigen presentation of neutralized virus particles and initiate adaptive immune responses against RSV.
authors: Department of Pediatrics, the Wilhelmina Children's Hospital, University Medical Center (UMC), Utrecht, The Netherlands.
authors: Debby
authors: D
authors: Kruijsen
authors: Helga K
authors: HK
authors: Einarsdottir
authors: Marcel A
authors: MA
authors: Schijf
authors: Frank E
authors: FE
authors: Coenjaerts
authors: Ellen C
authors: EC
authors: van der Schoot
authors: Gestur
authors: G
authors: Vidarsson
authors: Grada M
authors: GM
authors: van Bleek
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D000281:Administration, Intranasal; D000704:Analysis of Variance; D000818:Animals; D057134:Antibodies, Neutralizing / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010851:Picrates; D060888:Real-Time Polymerase Chain Reaction; D011961:Receptors, Fc / Q000235:genetics; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014771:Virion / Q000235:genetics / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D016207:Cytokines; D017931:DNA Primers; D015395:Histocompatibility Antigens Class I; D010851:Picrates; D011961:Receptors, Fc; C005858:picric acid; C100688:Fc receptor, neonatal
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