Monophosphoryl lipid A adjuvant reverses a principal histologic parameter of formalin-inactivated respiratory syncytial virus vaccine-induced disease.
The mechanisms by which administration of a formalin-inactivated respiratory syncytial virus vaccine resulted in enhanced disease among children after they later became naturally infected with the virus remains largely undefined. After immunization and live virus challenge, the cotton rat demonstrated the histopathologic marker of the enhanced disease, polymorphonuclear leukocyte infiltration of lung alveolar spaces. We now report that immunization with formalin-inactivated vaccine formulated with the adjuvant, 3-deacylated monophosphoryl lipid A, dramatically reduces or eliminates the polymorphonuclear leukocyte infiltration within the alveoli of cotton rats post-challenge. We suggest, that this or similar adjuvants may be beneficial components of candidate non-replicating respiratory syncytial virus vaccines, whose development has been hampered by safety concerns.
Prince
G A
GA
Virion Systems Inc., Rockville, MD 20850, USA. gprince@erols.com
Denamur
F
F
Deschamps
M
M
Garçon
N
N
Prieels
J P
JP
Slaoui
M
M
Thiriart
C
C
Porter
D D
DD
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D002648:Child; D005260:Female; D005557:Formaldehyde; D006801:Humans; D008050:Lipid A / Q000008:administration & dosage* / Q000031:analogs & derivatives; D008297:Male; D011650:Pulmonary Alveoli / Q000473:pathology; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D012449:Safety; D016205:Sigmodontinae; D015164:Vaccines, Inactivated / Q000009:adverse effects / Q000633:toxicity; D014765:Viral Vaccines / Q000009:adverse effects* / Q000633:toxicity*
D000276:Adjuvants, Immunologic; D008050:Lipid A; D015164:Vaccines, Inactivated; D014765:Viral Vaccines; D005557:Formaldehyde; C048436:monophosphoryl lipid A