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An In vitro Model to Study Immune Responses of Human Peripheral Blood Mononuclear Cells to Human Respiratory Syncytial Virus Infection
Published on: December 11, 2013
Single intranasal immunization with recombinant adenovirus-based vaccine induces protective immunity against
Jae-Rang Yu1, Sol Kim, Jee-Boong Lee
1College of Pharmacy, Ewha Womans University, 11-1 Dae-Hyun Dong, Seo-Dae-Mun Gu, Seoul 120-750, Korea.
Insights
A novel intranasal vaccine using a recombinant adenovirus expressing Respiratory Syncytial Virus (RSV) G glycoprotein shows potent, long-lasting protection against RSV infection in mice. This vaccine elicits strong mucosal immunity with reduced side effects compared to other methods.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Respiratory Syncytial Virus (RSV) is a leading cause of severe lower respiratory tract infections in infants and young children.
- Currently, no licensed vaccine is available for RSV prevention.
- The RSV G glycoprotein is a key target for developing effective vaccines due to its role in viral attachment.
Purpose of the Study:
- To construct and evaluate a novel recombinant replication-deficient adenovirus-based vaccine (rAd/3xG) expressing the soluble core domain of the RSV G glycoprotein.
- To assess the vaccine's efficacy and immunogenicity in a murine model.
- To compare the immune response induced by intranasal administration of rAd/3xG with other administration routes and a different vaccine approach.
Main Methods:
- Construction of a recombinant replication-deficient adenovirus (rAd/3xG) engineered for high expression of the RSV G glycoprotein core domain.
- Intranasal, intramuscular, and oral immunization of mice with rAd/3xG.
- Evaluation of protection against RSV challenge, duration of immunity, and induction of mucosal immunoglobulin A (IgA) responses.
- Analysis of CD4 T cell responses (gamma interferon and interleukin-4) and assessment of lung eosinophilia and vaccine-induced weight loss.
Main Results:
- A single intranasal immunization with rAd/3xG provided potent and sustained protection against RSV challenge for over 10 weeks.
- Strong mucosal IgA responses were induced by intranasal administration, but not by intramuscular or oral routes.
- rAd/3xG immunization did not elicit detectable gamma interferon- or interleukin-4-producing CD4 T cells in the lungs upon challenge.
- Compared to a vaccinia virus-based vaccine, rAd/3xG induced significantly lower lung eosinophilia and vaccine-induced weight loss.
Conclusions:
- Single intranasal administration of the rAd/3xG vaccine elicits robust protective immunity against RSV infection in a murine model.
- The vaccine is effective at inducing strong mucosal immune responses, suggesting potential for preventing RSV at the portal of entry.
- rAd/3xG represents a promising vaccine candidate for RSV, offering potent protection with a favorable safety profile regarding T cell responses and inflammatory markers.
Abstract:
Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract disease in infancy and early childhood. Despite its importance as a pathogen, there is no licensed vaccine against RSV. The G glycoprotein of RSV, a major attachment protein, is a potentially important target for protective antiviral immune responses. Here, a recombinant replication-deficient adenovirus-based vaccine, rAd/3xG, expressing the soluble core domain of G glycoprotein (amino acids 130 to 230) engineered by codon optimization and tandem repetition for higher-level expression, was constructed and evaluated for its potential as an RSV vaccine in a murine model. A single intranasal immunization with rAd/3xG provided potent protection against RSV challenge which lasted for more than 10 weeks. Strong mucosal immunoglobulin A responses were also induced by a single intranasal immunization but not by intramuscular or oral administration of rAd/3xG. Interestingly, neither gamma interferon- nor interleukin-4-producing CD4 T cells directed to I-E(d)-restricted epitope were detected in the lungs of rAd/3xG-immune mice upon challenge, whereas priming with vaccinia virus expressing RSV G (vvG) elicited strong Th1/Th2 mixed CD4 T-cell responses. Lung eosinophilia and vaccine-induced weight loss were significantly lower in the rAd/3xG-immune group than in the vvG-primed group. Together, our data demonstrate that a single intranasal administration of rAd/3xG elicits beneficial protective immunity and represents a promising vaccine regimen against RSV infection.
