Newly Developed RSV Vaccine Offers Immunity While Lowering the Risk of Dangerous Pulmonary Inflammation


Researchers at Artificial Cell Technologies (ACT) have created a wholly synthetic RSV microparticle vaccine that, when administered to mice, produced a protective immune response while also reducing pulmonary inflammation. In the journal Vaccines, further findings from their preclinical research have been revealed.

The possibility for severe pulmonary inflammation defined by bronchiolitis and pneumonia is a significant risk factor for RSV infection. Due to these severe problems, more than 200,000 youngsters and senior citizens are hospitalized in the US every year. Concerns about vaccine-enhanced respiratory disease (VERD), which occurs when vaccinated people who contract the virus experience worse lung inflammation than those who are unprotected, have prevented the development of an RSV vaccine. When more vaccinated children were hospitalized following RSV infection compared to unvaccinated children, clinical trials of a formalin-inactivated (FI-RSV) vaccine were stopped in the 1960s. No RSV vaccine has been authorized since that time.

“An effective RSV vaccine must protect against infection without priming the host for excessive inflammation,” He and his colleagues used ACT’s patented Layer-by-Layer (LbL) nanofilm technology to modify their synthetic RSV microparticle vaccine by adding a molecule known as a TLR2 ligand that influences the body’s inflammatory immune response.

Jeff Powell, Ph.D., Vice President of Immunology at ACT

The results of the modified vaccine’s testing in mice were astounding. It gave protection from RSV infection at a dose 30 times lower than the initial vaccine while triggering a stronger immune response (detected by antibody testing), reducing lung inflammation (measured by white blood cells called eosinophils), and lowering lung inflammation.

“We showed that, with a very simple modification, we were able to guide the immune system’s response to our vaccine,” 

Jeff Powell, Ph.D., Vice President of Immunology at ACT

The attachment G protein, which binds to a human cell, and the fusion F protein are the two main proteins on the surface of the RSV virus that play a role in infection (which opens up and delivers the viral payload). If a vaccine-induced immune response stops one of these proteins, infection is avoided.

The G protein synthetic antigen in the ACT microparticle vaccine stimulates host antibodies that prevent viral attachment to host target cells. (Other RSV vaccines that are now in the late stages of development target the viral F protein.) While the innate (non-specific) immune response may still cause inflammatory Th2-type mechanisms that are thought to be partially to blame for the VERD in immunized infants in the 1960s, the adaptive (virus-specific) immune response is still sufficient to minimise viral infection.

Powell and his associates aimed to lessen the possibly damaging Th2-type inflammatory response while simultaneously boosting the effectiveness of their G-protein vaccination. To do this, a TLR2 ligand was included in the vaccine to activate the innate response appropriately and reroute the adaptive response away from the more inflammatory Th2-type and toward the less inflammatory Th1-type. The ACT team injected mice with one of two microparticle possibilities (one with the TLR2 ligand and one without), then infected the mice with RSV to test their hypothesis that the modified microparticle would protect the host from both infection and excessive inflammation.

Mice that received the modified vaccine showed noticeably higher levels of G-specific antibodies, total protection from viral infection at a dose that was 30 times lower than that of the original unmodified vaccine, a change from an inflammatory Th2 profile to a protective Th1 profile in the lung cytokine/chemokine content, and a notable decrease in post-challenge pulmonary eosinophil infiltration.

“Too often, we focus solely on eliciting pathogen-specific immune responses without consideration of how undesirable inflammatory responses may complicate matters in the host”, “While other companies are nearing approval for RSV vaccines focused on the fusion (F) protein of the virus, there is a need to improve understanding of post-vaccination, post-infection immunity in respiratory diseases. We hope our research provides guidance in that regard.”

Jeff Powell, Ph.D., Vice President of Immunology at ACT

A grant from the National Institutes of Allergy and Infectious Diseases (1R43AI092924-01) provided funding for ACT’s joint study with Dr. Ralph Tripp of the University of Georgia College of Veterinary Medicine. The article can be found in the journal Vaccines’ Volume 10, Issue 12.

A biotechnology business in the development stage called Artificial Cell Technologies, Inc. creates totally synthetic vaccinations using its own Layer-by-Layer (LbL) technique, which uses ultra-thin polypeptide nanofilms coated on a calcium carbonate core. Because there are no biological production systems used in the entirely synthetic manufacturing platform, there are fewer chances of contamination and fewer steps in the production process. Scientists may quickly design, alter, and produce vaccines using ACT’s effective technology in a fraction of the time and space needed by more conventional platforms.

With a mission to revolutionize the way vaccines are designed, ACT’s technology offers what Chief Executive Officer Donald Masters, Ph.D., calls a “plug and play approach” to designing vaccines. “The majority of our process is the same, regardless of what the target is. From one vaccine to another, the core and the multilayer film of our microparticle don’t change. The only difference is the antigenic peptide that we add in the outermost layer of the film.”

A malaria vaccine candidate that has recently finished Phase 1a clinical evaluation, confirming safety and immunogenicity of the platform in adult human volunteers, is also part of the company’s product pipeline in addition to the RSV vaccine candidate. A Phase 1b controlled human malaria infection (CHMI) clinical trial of ACT’s malaria vaccine is currently being prepared.

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