Viral Nanostructures: Versatile Tool for Vaccine Development

Vaccines based on viral nanostructures are superior to conventional “classical” vaccines due to their safety and comparatively mild side effects.

Key takeaways:
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    Vaccines based on viral nanostructures are safer than classical vaccines because they do not contain the virus’s genetic material.
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    These vaccines usually have milder side effects which are limited to the pain in the injection area.
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    To date, only a handful of vaccines based on viral nanostructures have been approved, such as against human papillomavirus, hepatitis B virus, malaria, and the hepatitis E virus.
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    Researchers hope vaccines based on viral nanostructures could be used against antibiotic-resistant bacteria A. baumannii.

To date, only a few vaccines based on viral nanostructures have been approved, but they are expected to be used in preventing infections of Acinetobacter baumannii, a highly prevalent and dangerous nosocomial bacterium, say researchers at Vilnius University’s Life Sciences Center (VU LSC) Assoc. Prof. Julija Armalytė, Dr. Aliona Avižinienė, and Dr. Rasa Petraitytė-Burneikienė.

Viral nanostructures don’t cause infection

Viral nanostructures are small nanoparticles composed of self-assembled viral proteins. Those nanostructures look identical or highly similar to native (real) viruses from which they are derived. However, unlike real viruses, viral nanostructures can be produced by synthesizing only viral proteins in bacteria, yeast, or other protein expression systems, says Dr. Avižinienė.

“When a large number of viral proteins are synthesized, they can spontaneously interact with each other and form viral nanostructures. They usually resemble a native virus in their morphology (appearance). However, the viral nanostructure is not equivalent to a live virus because the nanostructure does not contain the virus’s genetic material, so these nanostructures, unlike real viruses, are not infectious and are safe once they enter the body,” she says.

According to the researcher, once in the body, viral nanostructures can trigger an immune response due to their morphological similarities to real viruses. Unmodified viral nanostructures can be and are already being used as licensed human vaccines; however, their application in science can be enhanced by attaching parts of other pathogens to their surface.

“While the majority of single proteins and protein fragments are non-immunogenic, this limitation of creating vaccines can be overcome by modifying viral nanostructures by attaching proteins or protein fragments of other pathogens on their surface. Due to a high number of repetitive protein fragments on the surface of nanostructures, these protein fragments become immunogenic, and it becomes easier for the immune system to recognize them and produce specific antibodies,” Dr. Avižinienė says.

Assoc. Prof. Armalytė notes that pathogen proteins alone could also be used as a vaccine.

“However, the immune system responds better when they are placed on viral nanostructures. A single small protein may go unnoticed by the immune system, but when presented on a viral nanostructure, it will be recognized as an “enemy.” This strategy helps create a stronger immune response compared with the use of a single protein,” she says.

Superior vaccines

According to Dr. Avižinienė, vaccines based on viral nanostructures are superior to conventional vaccines that have been used for years.

“In the classical vaccines, there is always a chance that the virus may not be fully attenuated or inactivated during vaccine preparation. Therefore, while effective, these vaccines are not entirely safe because there is a small risk that the attenuated virus may become virulent or the chemical inactivation of the virus during vaccine preparation may not be complete. Meanwhile, vaccines based on viral nanostructures are considered safe and effective,” she says.

"RNA vaccines used during the COVID-19 pandemic are often feared because they introduce genetic material into the body. However, the likelihood of this adversely affecting a person is very low. Meanwhile, viral nanostructure-based vaccines do not contain genetic material, only a protein that cannot affect the human genome."

Assoc. Prof. Julija Armalytė

Dr. Petraitytė-Burneikienė says that RNA vaccines are known to have caused undesirable side effects in many people. On the other hand, the side effects of a protein vaccine are usually milder and are limited to pain in the injection area.

According to Dr. Avižinienė, there is a strong global interest in viral nanostructures. Still, only a handful of vaccines are currently approved by the World Health Organization, including vaccines for human papillomavirus, hepatitis B virus, malaria, and the hepatitis E virus vaccine in China.

Antibiotic-resistant pathogen

Researchers at VU LSC are now conducting a study to determine whether vaccines based on viral nanostructures could protect against Acinetobacter baumannii.

It’s an opportunistic pathogen that attacks people with weakened immune systems. Moreover, being a nosocomial pathogen, it attacks hospitalized people. You cannot acquire it from the environment, but you can contract the pathogen from a catheter, touching curtains previously touched by infected patients, etc.

Furthermore, this bacterium is not easily “killed” — unlike most others, it takes a long time to dry out in the air.

“In 2017, the World Health Organization listed A. baumannii as one of the most dangerous pathogens for human health. Upon entering a weakened body, it usually causes pneumonia or even sepsis – a blood infection – which makes it particularly dangerous for hospitalized people with chronic illnesses. The pathogen is highly resistant to antibiotics, and the lack of efficient antibiotics makes it difficult to treat people with weakened immune systems. In this case, vaccines can be an alternative to antibiotics,” says Armalytė.

Vaccine against dangerous bacteria

Researchers at VU are conducting the study “Development of a virus-like particles-based vaccine against Acinetobacter baumannii,” part of the Lithuanian National Science Programme “Healthy Ageing,” trying to produce a safe vaccine using specific proteins from the A. baumannii pathogen.

In previous studies carried out in the laboratory of the LSC’s Institute of Biomedical Sciences, Dr. Jūratė Skerniškytė investigated various proteins of A. baumannii that determine the bacterium’s ability to colonize the human body.

“Skerniškytė found a protein called adhesin, responsible for making bacteria stick to surfaces. It turns out to be very conservative, occurring in all variants of A. baumannii. Vaccines are developed using surface proteins to help the immune system quickly recognize and destroy the bacterium.

A fragment of the surface adhesin protein was therefore taken for analysis. In her research, she found that the fragment conferred partial resistance to infection in mice. 60% of mice managed to survive. But it’s not 100%, so we are trying to improve the part of the protein used for the vaccine by taking different protein fragments and attaching them to viral nanostructures. We hope this will lead to stronger immunity, leading to all mice surviving the infection,” Armalytė says.

According to the researcher, some mice have already been immunized and have developed adequate immunity. Preliminary studies show that vaccination with modified viral nanostructures helps them to survive the infection.

The article was first published in Vilnius University's popular science magazine "Spectrum."

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