title: Infection-enhancing lipopeptides do not improve intranasal immunization of cotton rats with a delta-G candidate live-attenuated human respiratory syncytial virus vaccine.
abstract: Development of live-attenuated human respiratory syncytial virus (HRSV) vaccines has proven to be difficult. Several vaccine candidates were found to be over-attenuated and displayed limited immunogenicity. Recently, we identified three synthetic cationic lipopeptides that enhanced paramyxovirus infections in vitro. The infection enhancement proved to be mediated by enhanced virus binding to target cells. We hypothesized that these lipopeptides can be used as adjuvants to promote immune responses induced by live-attenuated paramyxovirus vaccines. This hypothesis was tested in a vaccination and challenge model in cotton rats, using a previously described recombinant live-attenuated candidate HRSV vaccine lacking the gene encoding the G glycoprotein (rHRSVΔG). Surprisingly, intranasal vaccination of cotton rats with rHRSVΔG formulated in infection-enhancing lipopeptides resulted in reduced virus loads in nasopharyngeal lavages, reduced seroconversion levels and reduced protection from wild-type HRSV challenge. In conclusion, we were unable to demonstrate the feasibility of lipopeptides as adjuvants for a candidate live-attenuated HRSV vaccine in the cotton rat model.
authors: Department of Viroscience; Erasmus MC; Rotterdam, The Netherlands.
authors: D
authors: D
authors: Tien Nguyen
authors: National Institute of Public Health and the Environment; Bilthoven, The Netherlands.
authors: Jolande
authors: J
authors: Boes
authors: Department of Viroscience; Erasmus MC; Rotterdam, The Netherlands; National Institute of Public Health and the Environment; Bilthoven, The Netherlands.
authors: Geert
authors: G
authors: van Amerongen
authors: National Institute of Public Health and the Environment; Bilthoven, The Netherlands.
authors: Yvonne
authors: Y
authors: van Remmerden
authors: Department of Viroscience; Erasmus MC; Rotterdam, The Netherlands.
authors: Selma
authors: S
authors: Yüksel
authors: National Institute of Public Health and the Environment; Bilthoven, The Netherlands.
authors: Teun
authors: T
authors: Guichelaar
authors: Department of Viroscience; Erasmus MC; Rotterdam, The Netherlands.
authors: Albert D M E
authors: AD
authors: Osterhaus
authors: Department of Viroscience; Erasmus MC; Rotterdam, The Netherlands.
authors: Rik L
authors: RL
authors: de Swart
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D004195:Disease Models, Animal; D007114:Immunization / Q000379:methods*; D055666:Lipopeptides / Q000008:administration & dosage*; D009305:Nasopharynx / Q000821:virology; D018357:Respiratory Syncytial Virus Infections / Q000517:prevention & control*; D022261:Respiratory Syncytial Virus Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D018113:Respiratory Syncytial Virus, Human / Q000235:genetics / Q000276:immunology*; D016205:Sigmodontinae; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D014759:Viral Envelope Proteins / Q000172:deficiency; D019562:Viral Load
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D055666:Lipopeptides; D022261:Respiratory Syncytial Virus Vaccines; D014613:Vaccines, Attenuated; D014759:Viral Envelope Proteins; C116204:attachment protein G
keywords: HRSV; adjuvant; lipopeptide; live-attenuated virus vaccine; paramyxovirus
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