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Int J Pharm . Subunit microparticulate vaccine delivery using microneedles trigger significant SARS-spike-specific humoral and cellular responses i

tetano

Editor, Senior Moderator
Int J Pharm


. 2023 Jan 4;122583.
doi: 10.1016/j.ijpharm.2023.122583. Online ahead of print.
Subunit microparticulate vaccine delivery using microneedles trigger significant SARS-spike-specific humoral and cellular responses in a preclinical murine model


Smital Patil[SUP] 1 [/SUP], Sharon Vijayanand[SUP] 1 [/SUP], Devyani Joshi[SUP] 1 [/SUP], Ipshita Menon[SUP] 1 [/SUP], Keegan Braz Gomes[SUP] 1 [/SUP], Akanksha Kale[SUP] 1 [/SUP], Priyal Bagwe[SUP] 1 [/SUP], Shadi Yacoub[SUP] 1 [/SUP], Mohammad N Uddin[SUP] 1 [/SUP], Martin J D'Souza[SUP] 2 [/SUP]



Affiliations

Abstract

The objective of this "proof-of-concept" study was to evaluate the synergistic effect of a subunit microparticulate vaccine and microneedles (MN) assisted vaccine delivery system against a human coronavirus. Here, we formulated PLGA polymeric microparticles (MPs) encapsulating spike glycoprotein (GP) of SARS-CoV as the model antigen. Similarly, we formulated adjuvant MPs encapsulating Alhydrogel® and AddaVax™. The antigen/ adjuvant MPs were characterized and tested in vitro for immunogenicity. We found that the antigen/ adjuvant MPs were non-cytotoxic in vitro. The spike GP MPs+Alhydrogel® MPs+AddaVax™ MPs showed enhanced immunogenicity in vitro as confirmed through the release of nitrite, autophagy, and antigen presenting molecules with their co-stimulatory molecules. Next, we tested the in vivo efficacy of the spike GP MP vaccine with and without adjuvant MPs in mice vaccinated using MN. The spike GP MPs+Alhydrogel® MPs+AddaVax™ MPs induced heightened spike GP-specific IgG, IgG1 and IgG2a antibodies in mice. Also, spike GP MPs+Alhydrogel® MPs+AddaVax™ MPs enhanced expression of CD4+ and CD8+ T cells in secondary lymphoid organ like spleen. These results indicated spike GP-specific humoral immunity and cellular immunity in vivo. Thus, we employed the benefits of both the subunit vaccine MPs and dissolving MN to form a non-invasive and effective vaccination strategy against human coronaviruses.
 
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