Subunit microparticulate vaccine delivery using microneedles trigger significant SARS-spike-specific humoral and cellular responses in a preclinical murine model

Patil, Smital; Vijayanand, Sharon; Joshi, Devyani; Menon, Ipshita; Gomes, Keegan Braz; Kale, Akanksha; Bagwe, Priyal; Yacoub, Shadi; Uddin, Mohammad Nasir; D’Souza, Martin J.

doi:10.1016/j.ijpharm.2023.122583

Cited by 11 publications

(13 citation statements)

References 40 publications

(37 reference statements)

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“…Thus, our novel transdermal vaccine has the potential to induce a cell-mediated immune response. This can be attributed to the Langerhans cells present in the skin that take up the antigen and stimulate the immune response by delivering the antigen to nearby lymph nodes [ 15 , 16 , 17 , 18 , 22 , 34 ]. However, in addition to CD4/CD8a expression, a detailed analysis of the cytokine profile is also necessary to supplement the cell-mediated immune response.…”

Section: Discussionmentioning

confidence: 99%

Zika Vaccine Microparticles (MPs)-Loaded Dissolving Microneedles (MNs) Elicit a Significant Immune Response in a Pre-Clinical Murine Model

et al. 2023

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Although the global Zika epidemic in 2015–16 fueled vaccine development efforts, there is no approved Zika vaccine or treatment available to date. Current vaccine platforms in clinical trials are administered via either subcutaneous or intramuscular injections, which are painful and decrease compliance. Therefore, in the present study, we explored Zika vaccine microparticles (MPs)-loaded dissolving microneedles (MNs) with adjuvant MPs encapsulating Alhydrogel® and MPL-A® administered via the transdermal route as a pain-free vaccine strategy. We characterized the MNs for needle length, pore formation, and dissolvability when applied to murine skin. Further, we evaluated the in vivo efficacy of vaccine MPs-loaded MNs with or without adjuvants by measuring the immune response after transdermal immunization. The vaccine MPs-loaded dissolving MNs with adjuvants induced significant IgG, IgG1, and IgG2a titers in immunized mice compared to the untreated control group. After the dosing regimen, the animals were challenged with Zika virus, monitored for seven days, and sacrificed to collect spleen and lymph nodes. The lymphocytes and splenocytes from the immunized mice showed significant expressions of helper (CD4) and cytotoxic (CD8a) cell surface markers compared to the control group. Thus, this study puts forth a ‘proof-of-concept’ for a pain-free transdermal vaccine strategy against Zika.

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Section: Discussionmentioning

confidence: 99%

Zika Vaccine Microparticles (MPs)-Loaded Dissolving Microneedles (MNs) Elicit a Significant Immune Response in a Pre-Clinical Murine Model

et al. 2023

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“…The percentage of antigen content in spike RBD MPs was measured using the Micro Bicinchoninic acid (BCA) assay according to the instructions from the manufacturer. The percentage of antigen content was measured as encapsulation efficiency using the following formula: Microneedles were formulated using the spin-casting method previously established in our laboratory [14,15,47,62,64]. First, depending on the group, the corresponding RBD suspension, RBD MPs, and adjuvant MPs were added to the trehalose solution.…”

Section: Preparation and Characterization Of Spike Rbd Microparticles...mentioning

confidence: 99%

“…Microparticles (MPs) formulated using biodegradable polymers such as poly(lactic-co-glycolic acid) (PLGA) have been studied as systems for the delivery of vaccine antigens [ 14 , 15 , 16 , 17 ], for soluble antigens like spike RBD, factors such as short half-life, low molecular size, and poor cross-presentation by activation of mainly the MHC-II pathway contribute towards the low immunogenic potential of the soluble antigen [ 16 , 17 , 18 , 19 , 20 , 21 ]. In contrast, encapsulating the antigen helps protect the antigen and increases cellular uptake by antigen-presenting cells (APCs) [ 22 , 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

“…CpG 7909 is a synthetic oligonucleotide that induces a Th1-biased immune response by activating CD4+ T cells to produce a robust antibody and mucosal response [ 34 , 35 ]. In previous studies, we have tested the effectiveness of adjuvants in the microparticulate form [ 14 , 36 ]. We observed that the microparticulate form of Alhydrogel ® and AddaVax™ were able to enhance antigen-specific humoral and cellular immune responses [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

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Adjuvanted-SARS-CoV-2 Spike Protein-Based Microparticulate Vaccine Delivered by Dissolving Microneedles Induces Humoral, Mucosal, and Cellular Immune Responses in Mice

et al. 2023

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COVID-19 continues to cause an increase in the number of cases and deaths worldwide. Due to the ever-mutating nature of the virus, frequent vaccination against COVID-19 is anticipated. Most of the approved SARS-CoV-2 vaccines are administered using the conventional intramuscular route, causing vaccine hesitancy. Thus, there is a need for an effective, non-invasive vaccination strategy against COVID-19. This study evaluated the synergistic effects of a subunit microparticulate vaccine delivered using microneedles. The microparticles encapsulated a highly immunogenic subunit protein of the SARS-CoV-2 virus, such as the spike protein’s receptor binding domain (RBD). Adjuvants were also incorporated to enhance the spike RBD-specific immune response. Our vaccination study reveals that a microneedle-based vaccine delivering these microparticles induced spike RBD-specific IgM, IgG, IgG1, IgG2a, and IgA antibodies. The vaccine also generated high levels of CD4+ and CD8a+ molecules in the secondary lymphoid organs. Overall, dissolving microneedles delivery spike RBD antigen in microparticulate form induced a robust immune response, paving the way for an alternative self-administrable, non-invasive vaccination strategy against COVID-19.

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“…There are several types of microneedles, such as solid microneedles and hollow microneedles; however, dissolving microneedles is one of the most sought-after methods of intradermal vaccination due to the fact of their versatility in loading different kinds of antigens [21]. Moreover, dissolving microneedles can also be loaded with different nanoparticles that will simply be released in the skin upon application [18,[22][23][24]. We have previously shown that when the F-VLP antigen is encapsulated into a PLGA polymeric nanoparticle matrix, it improves the immunogenicity in vitro [25].…”

Section: Introductionmentioning

confidence: 99%

Dissolving Microneedles Loaded with Nanoparticle Formulation of Respiratory Syncytial Virus Fusion Protein Virus-like Particles (F-VLPs) Elicits Cellular and Humoral Immune Responses

et al. 2023

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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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Subunit microparticulate vaccine delivery using microneedles trigger significant SARS-spike-specific humoral and cellular responses in a preclinical murine model

Cited by 11 publications

References 40 publications

Zika Vaccine Microparticles (MPs)-Loaded Dissolving Microneedles (MNs) Elicit a Significant Immune Response in a Pre-Clinical Murine Model

Zika Vaccine Microparticles (MPs)-Loaded Dissolving Microneedles (MNs) Elicit a Significant Immune Response in a Pre-Clinical Murine Model

Adjuvanted-SARS-CoV-2 Spike Protein-Based Microparticulate Vaccine Delivered by Dissolving Microneedles Induces Humoral, Mucosal, and Cellular Immune Responses in Mice

Dissolving Microneedles Loaded with Nanoparticle Formulation of Respiratory Syncytial Virus Fusion Protein Virus-like Particles (F-VLPs) Elicits Cellular and Humoral Immune Responses

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