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.
journal_name
Hum Vaccin Immunotherjournal_title
Human vaccines & immunotherapeuticsauthors
Tien Nguyen D,Boes J,van Amerongen G,van Remmerden Y,Yüksel S,Guichelaar T,Osterhaus AD,de Swart RLdoi
10.4161/hv.26096subject
Has Abstractpub_date
2013-12-01 00:00:00pages
2578-83issue
12eissn
2164-5515issn
2164-554Xpii
26096journal_volume
9pub_type
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