Stable Recombinant Invasion Plasmid Antigen C (IpaC)-Based Single Dose Nanovaccine for Shigellosis

Abstract

Shigellosis, caused by the bacteria Shigella, is the leading cause of bacterial diarrhea and the second leading cause of diarrheal death among children under the age of five. Unfortunately, Shigella strains have acquired resistance to antibiotics, and a commercial vaccine is yet to be available. We have previously demonstrated that Shigella dysenteriae serotype 1 (Sd1)-based recombinant, stabilized, "invasion plasmid antigen C" (IpaC; 42 kDa) protein can induce robust immune responses in BALB/c mice against a challenge of a high dose of heterologous Shigella when immunized via three intranasal doses of IpaC without an adjuvant. In this work, in order to reduce the frequency of dosing and increase possible patient compliance, based on our previous screening, the minimum protective dose of stabilized IpaC (20 μg) was encapsulated in biodegradable polymeric poly(lactide-co-glycolide) nanoparticles (∼370 nm) and intranasally administered in BALB/c mice in a single dose. Interestingly, a single intranasal dose of the developed vaccine particles encapsulating only 20 μg of Sd1 IpaC led to a temporal increase in the antibody production with an improved cytokine response compared to free IpaC administered three times as described in our previous report. Upon intraperitoneal challenge with a high dose of heterologous Shigella flexneri 2a (common in circulation), the immunized animals were protected from diarrhea, lethargy, and weight loss with ∼67% survival, while all the control animals died by 36 h of the challenge. Overall, the developed nanovaccine could be explored as a potential noninvasive, cross-protective, single-dose, single-antigen Shigella vaccine amenable for scale-up and eventual mass immunization.

Broad and Durable Humoral Responses Following Single Hydrogel Immunization of SARS‐CoV‐2 Subunit Vaccine

“…[3] Nonetheless, by 6 months, the binding antibody titers decreased to prebooster magnitude, and additional boosters were necessary to confer robust protection. [3] While there are a few reports on the development of single-shot nanovaccines, [35][36][37] an antigen-agnostic approach is necessary for a rapidly employable vaccine platform to combat emerging infectious diseases. Therefore, the present study reports the development of a new vaccine platform strategy that could elicit potent, broad, and durable humoral responses without the need for booster shots.…”

Facile synthesis of multi-faceted, biomimetic and cross-protective nanoparticle-based vaccines for drug-resistant Shigella: a flexible platform technology

“…The biocompatible and biodegradable poly (lactide- co -glycolide) or PLGA is one of the most widely explored safe (FDA approved for a few drug delivery applications) [ 37 ] polymers for drug/antigen delivery systems with known adjuvanticity [ 38 – 44 ]. However, surprisingly, it has limited exploration for Shigella vaccine development wherein only a handful of studies involving nanoparticulate-delivery systems have been reported [ 45 – 48 ]. Size of such polymeric systems can also significantly affect cellular uptake and immune cell activation.…”