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: D Tien Nguyen, Jolande Boes, Geert van Amerongen, Yvonne van Remmerden, Selma Yüksel, Teun Guichelaar, Albert D M E Osterhaus, Rik L de Swart
• Journal: Human vaccines & immunotherapeutics (Hum Vaccin Immunother) Vol. 9 Issue 12 Pg. 2578-83 (Dec 2013) ISSN: 2164-554X [Electronic] United States
• PMID: 23955280 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Immunologic
• Antibodies, Viral
• Lipopeptides
• Respiratory Syncytial Virus Vaccines
• Vaccines, Attenuated
• Viral Envelope Proteins
• attachment protein G

Topics

• Adjuvants, Immunologic (administration & dosage)
• Administration, Intranasal
• Animals
• Antibodies, Viral (blood)
• Disease Models, Animal
• Immunization (methods)
• Lipopeptides (administration & dosage)
• Nasopharynx (virology)
• Respiratory Syncytial Virus Infections (prevention & control)
• Respiratory Syncytial Virus Vaccines (administration & dosage, immunology)
• Respiratory Syncytial Virus, Human (genetics, immunology)
• Sigmodontinae
• Vaccines, Attenuated (administration & dosage, immunology)
• Viral Envelope Proteins (deficiency)
• Viral Load