Shigella bacteria, which causes Shigellosis, is the primary cause of bacterial diarrhea and diarrheal death among juveniles under five years of age. Because of the antibiotic resistance of Shigella strains, no commercial vaccines are available to date.
An article published in Molecular Pharmaceutics presented an extension of a previous work that demonstrated the stabilization of “invasion plasmid antigen C” (IpaC) protein by using Shigella dysenteriae serotype 1 (Sd1)-based recombinant to induce immune responses in BALB/c mice. However, this work involved the administration of three intranasal doses of IpaC without an adjuvant.
The aim of this study was to increase patient compliance by reducing the dosing frequency. Based on previous screening results, the optimal protective dose of stabilized IpaC, 20 micrograms was encapsulated in biodegradable polymeric poly(lactide-co-glycolide) (PLGA) nanoparticles with approximately 370 nanometers in size and a single-dose nanovaccine was administered intranasally into BALB/c mice.
The results revealed a temporal increase in antibody production with improved cytokine response via nanovaccine administration compared to free IpaC, which was administered three times in a previous study. The vaccinated animals were protected from diarrhea, lethargy, and weight loss upon intraperitoneal challenge with a high dose of heterologous Shigella flexneri 2a, whereas all the control animals died within 36 hours after the challenge.
Overall, the created nanovaccine could be investigated as a potential non-invasive, cross-protective, single-dose, single-antigen Shigella vaccine that is scalable and eventually suitable for mass vaccination.
Shigellosis and Development of Nanovaccine
Shigellosis is an intestinal infection caused by Shigella bacteria. Symptoms generally start one to two days after exposure and include diarrhea, fever, abdominal pain, and the need to pass stools, even when the bowels are empty.
Most Shigella strains develop resistance to many antibiotics. Since an approved vaccine is still unavailable, formulating an effective Shigella vaccine candidate has been declared a public health priority by the World Health Organization (WHO).
Nanotechnology plays a unique role in vaccine design by providing them with enhanced specificity and potency. Nanoparticles of less than 500 nanometers are quickly taken up by antigens and hence serve as potential carriers for delivering vaccine antigens and adjuvants. Nanoparticles have advantages, such as improved antigen stability, targeted delivery, and long-term release, for which antigens/adjuvants are either encapsulated within or decorated on the surface of a nanoparticle.
Nanovaccine exhibits unique physicochemical characteristics. The role of a nanovaccine as a potent vaccine has been examined to boost their therapeutic activity by enhancing their stability, prolonging their circulation and site-specific accumulation, increasing their delivery according to various biological and external stimuli, and overcoming physiological barriers.
As an active immunogenic material that modulates the immune response, a nanovaccine enables antigen stability, enhances antigen processing and immunogenicity with targeted delivery, and prevents the burst release of antigens and adjuvants.
IpaC-Based Single Dose Nanovaccine for Shigellosis
Although there has been a great deal of effort to develop a Shigella vaccine that is both safe and effective, none has been clinically approved. Although conserved recombinant subunit vaccines can be cross-protective in nature, adjuvants are required to provide sufficient immunogenicity, which may present safety issues.
Furthermore, the administration of multiple doses of subunit proteins along with adjuvants in previous studies did not result in sufficient immunogenicity and effective cross-protection. Previously, a self-adjuvant vaccine was created by stabilizing IpaC, an unstable conserved recombinant Shigella protein. Three intranasal doses of stabilized Shigella dysenteriae IpaC resulted in 100% survival when challenged with heterologous Shigella flexneri.
The present study was a step toward extending the shelf life of stabilized IpaC and lowering the dose frequency to boost patient compliance. Here, a previously determined minimum protective dose, 20 micrograms of IpaC, was administered intranasally as a single dose nanovaccine, wherein a biodegradable PLGA polymer was used to formulate the nanovaccine.
Additionally, because PLGA shows adjuvant properties owing to the depot effect, it avoids the need for an additional adjuvant. Thus, utilizing PLGA nanoparticles to deliver Shigella proteins helps to develop a minimalist single-antigen nanovaccine against Shigella.
The developed PLGA 50:50 nanoparticles released up to 77% of the encapsulated protein in 28 days at 37 degrees Celsius and were degraded in 35 days under physiological conditions. Following the administration of the nanovaccine, the nanoparticles were lyophilized effectively and transported, which was desirable for translatable vaccines.
Furthermore, IgG and IgA titers increased with time, indicating sustained release of IpaC from the nanovaccine. Ultimately, the single-dose nanovaccine encapsulating 20 micrograms of stabilized IpaC showed potential as a non-invasive, single-antigen nanovaccine against Shigella.
Conclusion
Overall, the present work provided evidence that encapsulating a minimum protective dose of stabilized S. dysenteriae IpaC protein in PLGA 50:50 nanoparticles results in a non-invasive, single-dose, single-antigen, cross-protective Shigella nanovaccine with scope for mass scale-up and immunization.
News
X Marks the Spot: AI’s Treasure Maps Lead to Early Disease Detection
Medical diagnostics expert, doctor’s assistant, and cartographer are all fair titles for an artificial intelligence model developed by researchers at the Beckman Institute for Advanced Science and Technology. Their new model accurately identifies tumors [...]
Scientists Discover Method To Identify Alzheimer’s Disease Before It Progresses to Dementia
Researchers at Aarhus University have discovered a method to identify Alzheimer’s disease before it progresses to dementia, potentially opening up new avenues for treatment. A groundbreaking study could pave the way for early detection [...]
Startling Discovery: COVID-19 Virus Can Stay in the Body More Than a Year After Infection
The COVID-19 virus can persist in the blood and tissue of patients for more than a year after the acute phase of the illness has ended, according to new research from UC San Francisco that offers potential [...]
New bioengineered protein design shows promise in fighting COVID-19
In the wake of the COVID-19 pandemic, scientists have been racing to develop effective treatments and preventatives against the virus. A recent scientific breakthrough has emerged from the work of researchers aiming to combat [...]
Sugar-coated gold nanoparticles can quickly eliminate bacterial infections, no antibiotics required
If left to their own devices, bacteria on our teeth or wounded skin can encase themselves in a slimy scaffolding, turning into what is called biofilm. These bacteria wreak havoc on our tissue and, [...]
Liquid Lightning: Nanotechnology Unlocks New Energy
EPFL researchers have discovered that nanoscale devices harnessing the hydroelectric effect can harvest electricity from the evaporation of fluids with higher ion concentrations than purified water, revealing a vast untapped energy potential. Evaporation is a natural [...]
Unmasking the Illusion: AI-Generated Faces Challenge Perceptions
Research shows survey participants duped by AI-generated images nearly 40 percent of the time. If you recently had trouble figuring out if an image of a person is real or generated through artificial intelligence [...]
New Discovery Reveals How Cells Defend Themselves During Stressful Situations
Stress granules play a crucial role in the stress response, arising from the aggregation of non-translating mRNAs and proteins. Although significant knowledge exists about stress granules, the mechanisms behind their mRNA localization remain partially [...]
Scientists use a new type of nanoparticle that can both deliver vaccines and act as an adjuvant
Many vaccines, including vaccines for hepatitis B and whooping cough, consist of fragments of viral or bacterial proteins. These vaccines often include other molecules called adjuvants, which help to boost the immune system's response [...]
Not Science Fiction: How Optical Neural Networks Are Revolutionizing AI
A novel architecture for optical neural networks utilizes wavefront shaping to precisely manipulate the travel of ultrashort pulses through multimode fibers, enabling nonlinear optical computation. Present-day artificial intelligence systems rely on billions of adjustable [...]
Turning skin cells into limb cells sets the stage for regenerative therapy
In a collaborative study, researchers from Kyushu University and Harvard Medical School have identified proteins that can turn or “reprogram” fibroblasts — the most commonly found cells in skin and connective tissue — into [...]
AI reveals prostate cancer is not just one disease
Artificial Intelligence has helped scientists reveal a new form of aggressive prostate cancer, which could revolutionise how the disease is diagnosed and treated in the future. A Cancer Research UK-funded study, published in Cell Genomics, has revealed [...]
New Study Finds That Persistent COVID-19 Infections Are Surprisingly Common
Recent research conducted by the University of Oxford has found that a high proportion of SARS-CoV-2 infections in the general population lead to persistent infections lasting a month or more. The findings have been published in the journal Nature. [...]
Innovative nanosheet method revolutionizes brain imaging for multi-scale and long-term studies
The human brain has billions of neurons. Working together, they enable higher-order brain functions such as cognition and complex behaviors. To study these higher-order brain functions, it is important to understand how neural activity [...]
Scientists Have Discovered a Potential Universal Antivenom
Scientists at Scripps Research identified antibodies that protect against a host of lethal snake venoms. Scripps Research scientists have developed an antibody that can block the effects of lethal toxins in the venoms of [...]
Scientists discover the human brain is even more powerful than we thought
The human brain could be far more powerful than we ever imagined, scientists have discovered. Researchers have identified cell messaging which have never been uncovered before, which suggests our brains are capable of more than previously realised. It’s [...]