Vaccination to induce antibodies blocking the CX3C-CX3CR1 interaction of respiratory syncytial virus G protein reduces pulmonary inflammation and virus replication in mice.
Respiratory syncytial virus (RSV) infection causes substantial morbidity and some deaths in the young and elderly worldwide. There is no safe and effective vaccine available, although it is possible to reduce the hospitalization rate for high-risk children by anti-RSV antibody prophylaxis. RSV has been shown to modify the immune response to infection, a feature linked in part to RSV G protein CX3C chemokine mimicry. This study determined if vaccination with G protein polypeptides or peptides spanning the central conserved region of the G protein could induce antibodies that blocked G protein CX3C-CX3CR1 interaction and disease pathogenesis mediated by RSV infection. The results show that mice vaccinated with G protein peptides or polypeptides containing the CX3C motif generate antibodies that inhibit G protein CX3C-CX3CR1 binding and chemotaxis, reduce lung virus titers, and prevent body weight loss and pulmonary inflammation. The results suggest that RSV vaccines that induce antibodies that block G protein CX3C-CX3CR1 interaction may offer a new, safe, and efficacious RSV vaccine strategy.
College of Veterinary Medicine, Department of Infectious Disease, 111 Carlton Street, University of Georgia, Athens, Georgia 30602, USA.
Wenliang
W
Zhang
Youngjoo
Y
Choi
Lia M
LM
Haynes
Jennifer L
JL
Harcourt
Larry J
LJ
Anderson
Les P
LP
Jones
Ralph A
RA
Tripp
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood* / Q000276:immunology; D000073883:CX3C Chemokine Receptor 1; D002460:Cell Line; D020523:Chemokines, CX3C / Q000276:immunology / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control; D008168:Lung / Q000276:immunology / Q000503:physiopathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology; D019707:Receptors, Chemokine / Q000276:immunology / Q000378:metabolism*; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000503:physiopathology / Q000821:virology; D022261:Respiratory Syncytial Virus Vaccines / Q000008:administration & dosage / Q000276:immunology; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology; D014611:Vaccination; D014760:Viral Fusion Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D014779:Virus Replication
D000914:Antibodies, Viral; D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D020523:Chemokines, CX3C; C502275:G glycoprotein, Respiratory syncytial virus; D010455:Peptides; D019707:Receptors, Chemokine; D022261:Respiratory Syncytial Virus Vaccines; D014760:Viral Fusion Proteins