An Adjuvanted Inactivated SARS-CoV-2 Microparticulate Vaccine Delivered Using Microneedles Induces a Robust Immune Response in Vaccinated Mice

Abstract

SARS-CoV-2, the causal agent of COVID-19, is a contagious respiratory virus that frequently mutates, giving rise to variant strains and leading to reduced vaccine efficacy against the variants. Frequent vaccination against the emerging variants may be necessary; thus, an efficient vaccination system is needed. A microneedle (MN) vaccine delivery system is non-invasive, patient-friendly, and can be self-administered. Here, we tested the immune response produced by an adjuvanted inactivated SARS-CoV-2 microparticulate vaccine administered via the transdermal route using a dissolving MN. The inactivated SARS-CoV-2 vaccine antigen and adjuvants (Alhydrogel® and AddaVax™) were encapsulated in poly(lactic-co-glycolic acid) (PLGA) polymer matrices. The resulting MP were approximately 910 nm in size, with a high percentage yield and percent encapsulation efficiency of 90.4%. In vitro, the vaccine MP was non-cytotoxic and increased the immunostimulatory activity measured as nitric oxide release from dendritic cells. The adjuvant MP potentiated the immune response of the vaccine MP in vitro. In vivo, the adjuvanted SARS-CoV-2 MP vaccine induced high levels of IgM, IgG, IgA, IgG1, and IgG2a antibodies and CD4+ and CD8+ T-cell responses in immunized mice. In conclusion, the adjuvanted inactivated SARS-CoV-2 MP vaccine delivered using MN induced a robust immune response in vaccinated mice.

Fourth dose of Microneedle Array Patch of SARS-CoV-2 S1 Protein Subunit Vaccine Elicits Robust Long-lasting Humoral Responses in mice

“…These include the assessment of T-cell specific cellular immune responses and conducting a SARS-CoV-2 challenge study to evaluate the protective effectiveness of a booster vaccination. Nevertheless, previous studies have shown that intradermal delivery of SARS-CoV-2 spike protein using dissolvable microneedle patches activated T-cell immunity (11, 12, 48). MAP S-RBD elicited significant B-cell and T-cell responses against S-RBD, comparable to conventional bolus injection (12).…”

“…To steer the IgG subclass toward a Th1-biased immune response, incorporating vaccine adjuvants is anticipated. Several studies have shown that adjuvanted SARS-CoV-2 MAP vaccines induce a balanced Th1/Th2 response in mice (11, 48, 49). Additionally, incorporating vaccine adjuvants can boost vaccine efficacy and conserve more vaccine doses (50).…”

Diphtheria Toxoid Particles as Q Fever Vaccine

“…DMSO (50%) was used as the negative control. [ 40 ] CPs ranging between 100 to 6.25 µg mL −1 , were then added in quadruplicates and incubated for a further 24 h, after which Alamar blue cell viability reagent was added (ThermoFisher Scientific, MA, USA) at a final concentration of 10% to determine cell viability. Following 8 h incubation, the absorbance was measured at 570 and 600 nm using BioTek Synergy H1 Hybrid Microplate reader (Bio‐Tek Instruments Inc., USA).…”