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Shigella vaccine research is a top priority for many researchers. Utah State University undergraduate Tristen Teeples is one of many working toward identifying vaccine mechanisms that will work on this harmful germ.
Shigella is the bacteria responsible for the illness called shigellosis. It isn’t typically fatal in developed countries; however, it is highly contagious and a significant concern in areas where clean water is scarce.
Worldwide, this infection is responsible for approximately 269 million illnesses and more than 200,000 deaths each year.
Most people begin to feel symptoms around 1 to 2 days after coming in contact with the bacteria and usually feel sick for around 5 to 7 days. In some cases, however, it may take months to fully recover.
Common symptoms include:
In some cases, people may not experience any symptoms at all.
While not usually fatal in the United States, people with diarrheal symptoms should contact their doctor if they have fever, bloody or prolonged diarrhea, severe stomach cramping or tenderness, or dehydration.
Certain people are more susceptible to illness or may experience prolonged illness. Those in poor health and those with weakened immune systems should contact their doctor immediately.
Most people will recover from shigellosis. However, certain serious complications may occur that can have a lasting effect.
Around 2% of people with certain types of Shigella infections (most commonly Shigella flexneri or Shigella sonnei) may develop reactive arthritis after infection. Certain people are more susceptible to reactive arthritis than others. This illness, which can cause joint pain, eye irritation, and painful urination usually lasts for 3 to 5 months, however it has been known to last for years and lead to chronic arthritis.
Somewhere between 0.4% and 7.3% of people with Shigella infections develop bloodstream infections. This happens when the Shigella bacteria damages the intestinal lining and makes their way into the bloodstream. This type of complication is more common in those with a weakened immune system such as people with HIV, diabetes, cancer, or severe malnutrition. Children are more likely to have shigellosis bloodstream infection than adults. Certain strains of the bacteria, such as Shigella flexneri and Shigella dysenteriae are more likely to result in bloodstream infections. Patients with this complication are at higher risk of death than others without this complication.
Hemolytic uremic syndrome, or HUS, is a rare complication of shigellosis. It is more common in children and causes a type of kidney failure. HUS occurs when the Shigella bacteria produces a toxin that destroys red blood cells. This can cause blockages in the kidneys that effects the filtering functions performed by the organ. HUS is the leading cause of death in Shigella dysenteriae outbreaks.
In underdeveloped or poverty-stricken communities where water and adequate sanitation are not available, outbreaks can cause widespread illness. This is particularly dangerous among the young and the elderly.
Add antibiotic resistance to the mix and you have a recipe for disaster.
Hence the need for a Shigella vaccine to help prevent these outbreaks.
The honor student and biochemistry major, Tristen Teeples, has been working with his faculty mentor, Nick Dickenson, for nearly a year.
His approach involves an invasion plasmid.
“I’m specifically studying invasion plasmid antigen D, known as ‘IpaD,’ a key protein in the Shegella Type Three secretion system. By isolating and studying this protein, he says he can better understand how it makes people sick and hopefully a solution to an effective vaccine.
He explains that the IpaD is used to help the bacteria invade the cell and defend against the host’s immune system. This protein is critical in the timing the bacteria need to invade their target. “These characteristics make understanding this protein crucial for determining how to develop a vaccine.”
This young researcher has already successfully isolated parts of the injection mechanisms to continue research on how it functions.
This is just one approach to creating a Shigella vaccine. There are several types of vaccine approaches, all with their own merits.
There are several basic strategies to designing vaccines. Certain approaches work better with one pathogen than with others.
One strategy is the weaken the virus. This is the approach in vaccines for measles, mumps, rubella, rotavirus, oral polio, chickenpox, and influenza (intranasal version). Weakening the virus reduces its ability to replicate. With fewer copies of the virus in the system, the host doesn’t become very sick if at all.
This exposes the body to the virus, where the immune system can respond to this weakened infection successfully and store that approach for later use.
This approach isn’t appropriate for people with immune systems such as those with cancer or AIDS.
Another strategy is to inactivate the virus. This involves killing the virus with a chemical so that it cannot reproduce itself in the host or cause disease. Vaccines for polio, hepatitis A, influenza, and rabies are made this way.
The body’s immune system is still exposed to the virus, so it can respond and store that approach for later use. However, it cannot cause illness in the vaccine recipient because the virus is not alive.
In some vaccines, just one part of the virus is removed and used as a vaccine. This is the case for hepatitis B, shingles, HPV, and one of the influenza vaccines. A surface protein from the virus is used in the vaccine. This type of vaccine can be given to those with a weakened immune system since the virus isn’t fully intact and alive.
In cases where a bacteria produces a harmful toxin, protection against the toxin is the priority. Some vaccines, such as those for diptheria, tetanus, and pertussis are made by inactivating the toxin produced by the bacteria and including it in the vaccine to engage an immune response.
Sometimes it is the sugar coating found on the bacteria that is used in the vaccine. As is the case for the haemophilus influenzae type B, pneumococcal, and some meningococcal vaccines.
These types of vaccines can be given to immunocompromised people, as the real organism is not used in the vaccine.
In some cases, such as the COVID-19 vaccine, parts of the genetic code are used. In this case, the spike protein was used in the vaccine, so that the person’s immune system will respond when it is encountered again.
As of right now, there is no licensed Shigella vaccine available. There are, however, several candidates that are being evaluated at various stages of preclinical and clinical development. Scientists, like Teeples, and countless others at various levels are working toward that goal.
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By: Heather Van Tassell (contributing writer, non-lawyer)
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