Immunoprotective activity and safety of a respiratory syncytial virus vaccine: mucosal delivery of fusion glycoprotein with a CpG oligodeoxynucleotide adjuvant.
CpG oligodeoxynucleotides (ODN) were identified that stimulated immunoglobulin production and cell proliferation in cotton rat cells in vitro. Three of these ODN were used as a mucosal adjuvant in the noses of cotton rats immunized via this route with respiratory syncytial virus fusion (F) protein. The CpG ODN markedly increased the cotton rat humoral neutralizing-antibody response to respiratory syncytial virus. Such immunized animals had a marked reduction in the production of infectious virus after a live-virus challenge. Animals immunized with the combination of F protein and CpG developed enhanced pulmonary pathology consisting of alveolitis and interstitial pneumonitis after a live-virus challenge. Similar enhanced disease has been seen in cotton rats and children immunized with formalin-inactivated respiratory syncytial virus.
Prince
Gregory A
GA
Virion Systems, Inc., Rockville, Maryland 20850, USA. gprince@erols.com
Mond
James J
JJ
Porter
David D
DD
Yim
Kevin C
KC
Lan
Steve J
SJ
Klinman
Dennis M
DM
D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D018899:CpG Islands / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007114:Immunization; D008168:Lung / Q000473:pathology; D008297:Male; D009092:Mucous Membrane; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000276:immunology*; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control / Q000821:virology; D022261:Respiratory Syncytial Virus Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology; D016205:Sigmodontinae; D014760:Viral Fusion Proteins / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D009838:Oligodeoxyribonucleotides; D022261:Respiratory Syncytial Virus Vaccines; D014760:Viral Fusion Proteins; D014764:Viral Proteins