Monophosphoryl lipid A adjuvant reverses a principal histologic parameter of formalin-inactivated respiratory syncytial virus vaccine-induced disease

• Published in: Vaccine Vol. 19; no. 15; pp. 2048 - 2054
• Main Authors: Prince, Gregory A., Denamur, Françoise, Deschamps, Marguerite, Garçon, Nathalie, Prieels, Jean-Paul, Slaoui, Moncef, Thiriart, Clothilde, Porter, David D.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 28.02.2001; Elsevier
• Subjects: Adjuvants; Adjuvants, Immunologic - administration & dosage; Alveolitis; Animals; Biological and medical sciences; Child; Female; Formaldehyde; Fundamental and applied biological sciences. Psychology; Humans; Lipid A - administration & dosage; Lipid A - analogs & derivatives; Male; Microbiology; monophosphoryl lipid A; Pulmonary Alveoli - pathology; respiratory syncytial virus; Respiratory Syncytial Virus Infections - immunology; Respiratory Syncytial Virus Infections - pathology; Respiratory Syncytial Virus Infections - prevention & control; Respiratory Syncytial Viruses - immunology; Safety; Sigmodon hispidus; Sigmodontinae; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Vaccines, Inactivated - adverse effects; Vaccines, Inactivated - toxicity; Viral Vaccines - adverse effects; Viral Vaccines - toxicity; Virology; Adjuvants; MPL, monophosphoryl lipid A; pfu, plaque forming units; Alveolitis; Sigmodon hispidus; RSV, respiratory syncytial virus; Human respiratory syncytial virus; Lung disease; Pneumovirinae; Respiratory disease; Toxicity; Rodentia; Inflammation; Vaccine; Property formulation relationship; Paramyxoviridae; Virus; Mononegavirales; Vertebrata; Mammalia; Immunological adjuvant; Pulmonary alveolus; Pneumovirus; Inactivated strain
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/S0264-410X(00)00417-5

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.