Abstract
Human parainfluenza viruses (HPIVs) are the etiologic agents of lower respiratory infections and pneumonia in infants, young children and immunocompromised hosts. The overarching goal for the prevention of HPIV infection is the development of an effective vaccine against HPIVs. In the present study, we investigated the effectiveness of oligomannose-coated liposomes (OMLs) as an antigen-delivery system in combination with a synthetic double-stranded RNA analog for the induction of mucosal and systematic immunity against HPIV3. Full-length hemagglutinin-neuraminidase (HN) protein was synthesized using the wheat germ cell-free protein production system and then encapsulated into OML to serve as the antigen. Intranasal administration of the HN-filling OML (OML-HN) with the synthetic double-stranded RNA adjuvant, polyriboinosinic-polyribocytidylic acid [poly(I:C)] generated significant viral-specific systemic and mucosal immune responses as evidenced by the prominent induction of serum IgG and nasal wash IgA, respectively. On the other hand, no significant immune responses were observed in mice immunized with OML-HN without the adjuvant. Furthermore, serum from mice immunized with OML-HN plus poly(I:C) significantly suppressed viral infection in cell culture model. Our results provide the first evidence that intranasal co-administration of OML-encapsulated HN with the poly(I:C) adjuvant augments the viral-specific immunity against HPIV3.
Highlights
Human parainfluenza viruses (HPIVs) belong to the Paramyxoviridae family and are one of the major causes of acute respiratory infections (ARIs) and asthma in infants and young children (
GENERATION OF oligomannose-coated liposomes (OMLs) VACCINE AGAINST human parainfluenza virus type 3 (HPIV3)-HN To produce the full-length HPIV3-HN antigen, we subcloned full-length HN cDNA into two different cell-free expression vectors, pEU-His and pEU-GST for the expression of Nterminally His-tagged or GST-tagged fusion proteins, respectively (Figure 1A). We found that both His-HN and GST-tagged HPIV3-HN (GST-HN) proteins were efficiently synthesized using the wheat germ cell-free system (Figures 1B,C)
The levels of HPIV3 mRNA were significantly reduced in cells pre-incubated with the immunized mouse serum compared to control serum that immunized with OML-empty (Figure 4C). These results indicate that the immunization with OML-HN plus Poly(I:C) induced serum antibodies that protect HPIV3 infection
Summary
Human parainfluenza viruses (HPIVs) belong to the Paramyxoviridae family and are one of the major causes of acute respiratory infections (ARIs) and asthma in infants and young children (
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
