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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 10, 2013
Dissolving Microneedles Loaded with Nanoparticle Formulation of Respiratory Syncytial Virus Fusion Protein Virus-like
Ipshita Menon1, Smital Patil1, Priyal Bagwe1
1Center for Drug Delivery Research, Vaccine Nanotechnology Laboratory, College of Pharmacy, Mercer University, Atlanta, GA 30341, USA.
Insights
Novel dissolving microneedles loaded with respiratory syncytial virus (RSV) nanoparticles effectively induced robust immune responses in mice. This innovative delivery system shows promise for future RSV vaccines.
Area of Science:
- Vaccinology and Immunology
- Biomaterials and Nanotechnology
Background:
- Respiratory syncytial virus (RSV) poses a significant health threat, causing severe respiratory illness in young children.
- Existing healthcare systems face a substantial burden due to frequent RSV outbreaks, highlighting the urgent need for effective vaccines.
- Novel vaccine delivery systems are crucial for developing next-generation infectious disease vaccines, including those for RSV.
Purpose of the Study:
- To evaluate the in vivo immunogenicity of a novel vaccine delivery system for RSV.
- To investigate the potential of polymeric nanoparticles encapsulated in dissolving microneedles for RSV vaccine delivery.
Main Methods:
- Virus-like particles of the RSV fusion protein (F-VLP) were encapsulated in poly (D, L-lactide-co-glycolide) (PLGA) nanoparticles (NPs).
- These F-VLP NPs were loaded into dissolving microneedles (MNs) composed of hyaluronic acid and trehalose.
- Mice were immunized intradermally with F-VLP NPs, with or without monophosphoryl lipid A (MPL) adjuvant NPs, loaded in the MNs, followed by RSV challenge.
Main Results:
- Mice immunized with F-VLP NPs and MPL NPs in MNs exhibited high levels of IgG and IgG2a antibodies in serum and lung homogenates.
- A significant IgA response in lung homogenates post-RSV challenge indicated a successful mucosal immune response.
- Flow cytometry revealed increased CD8+ and CD4+ T-cell expression in lymph nodes and spleens of immunized mice.
Conclusions:
- The study demonstrates that PLGA nanoparticles loaded in dissolving microneedles can elicit a robust humoral and cellular immune response against RSV.
- This nanoparticle-loaded microneedle system represents a promising novel delivery platform for developing effective RSV vaccines.
Abstract:
Respiratory syncytial virus (RSV) is one of the leading causes of bronchiolitis and pneumonia in children ages five years and below. Recent outbreaks of the virus have proven that RSV remains a severe burden on healthcare services. Thus, a vaccine for RSV is a need of the hour. Research on novel vaccine delivery systems for infectious diseases such as RSV can pave the road to more vaccine candidates. Among many novel vaccine delivery systems, a combined system with polymeric nanoparticles loaded in dissolving microneedles holds a lot of potential. In this study, the virus-like particles of the RSV fusion protein (F-VLP) were encapsulated in poly (D, L-lactide-co-glycolide) (PLGA) nanoparticles (NPs). These NPs were then loaded into dissolving microneedles (MNs) composed of hyaluronic acid and trehalose. To test the in vivo immunogenicity of the nanoparticle-loaded microneedles, Swiss Webster mice were immunized with the F-VLP NPs, both with and without adjuvant monophosphoryl lipid A (MPL) NPs loaded in the MN. The mice immunized with the F-VLP NP + MPL NP MN showed high immunoglobulin (IgG and IgG2a) levels both in the serum and lung homogenates. A subsequent analysis of lung homogenates post-RSV challenge revealed high IgA, indicating the generation of a mucosal immune response upon intradermal immunization. A flowcytometry analysis showed high CD8+ and CD4+ expression in the lymph nodes and spleens of the F-VLP NP + MPL NP MN-immunized mice. Thus, our vaccine elicited a robust humoral and cellular immune response in vivo. Therefore, PLGA nanoparticles loaded in dissolving microneedles could be a suitable novel delivery system for RSV vaccines.
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