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Intranasal Administration of Recombinant Influenza Vaccines in Chimeric Mouse Models to Study Mucosal Immunity
Published on: June 25, 2015
Development of oligomannose-coated liposome-based nasal vaccine against human parainfluenza virus type 3
Kyosuke Senchi1, Satoko Matsunaga, Hideki Hasegawa
1Department of Microbiology, Yokohama City University School of Medicine, Yokohama, Kanagawa Japan.
Insights
Oligomannose-coated liposomes carrying HPIV3 hemagglutinin-neuraminidase protein, combined with a poly(I:C) adjuvant, effectively induce systemic and mucosal immunity against Human parainfluenza virus type 3.
Area of Science:
- Virology
- Immunology
- Vaccine Development
Background:
- Human parainfluenza viruses (HPIVs) cause severe respiratory infections in vulnerable populations.
- Developing an effective HPIV vaccine is crucial for prevention.
- Current prevention strategies for HPIVs are limited.
Purpose of the Study:
- To evaluate oligomannose-coated liposomes (OMLs) as a delivery system for HPIV3 antigen.
- To assess the immunogenicity of OML-encapsulated HPIV3 hemagglutinin-neuraminidase (HN) protein with a poly(I:C) adjuvant.
- To determine the capacity of this formulation to induce protective immunity against HPIV3.
Main Methods:
- Synthesized full-length HPIV3 HN protein using a wheat germ cell-free system.
- Encapsulated HN protein into OMLs for antigen delivery.
- Administered OML-HN with or without poly(I:C) adjuvant intranasally in a mouse model.
Main Results:
- Intranasal co-administration of OML-HN and poly(I:C) induced significant HPIV3-specific systemic IgG and mucosal IgA responses.
- Immunization with OML-HN alone did not elicit significant immune responses.
- Serum from immunized mice demonstrated viral infection suppression in a cell culture model.
Conclusions:
- Oligomannose-coated liposomes serve as an effective antigen-delivery system for HPIV3.
- Co-administration with poly(I:C) adjuvant significantly enhances HPIV3-specific mucosal and systemic immunity.
- This intranasal vaccine approach holds promise for HPIV3 prevention.
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.
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