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

Promising results of preclinical research on a fully synthetic vaccine designed by Artificial Cell Technologies are published in the journal Vaccines

NEW HAVEN, Conn., Jan. 30, 2023 /PRNewswire/ -- Scientists at Artificial Cell Technologies (ACT) have developed a fully synthetic microparticle vaccine for Respiratory Syncytial Virus (RSV)  that elicited a protective immune response in mice while simultaneously lowering pulmonary inflammation after exposure to the virus. New results of their preclinical research have been published in the journal Vaccines.

A major risk of RSV infection is the potential for severe pulmonary inflammation characterized by bronchiolitis and pneumonia. Each year, more than 200,000 children and older adults are hospitalized in the United States due to these serious complications. Efforts to develop an RSV vaccine have been hampered by concerns over vaccine-enhanced respiratory disease (VERD) – a condition that arises when vaccinated individuals who become infected with the virus develop worse pulmonary inflammation than those who are unvaccinated. In the 1960s, clinical trials of a formalin-inactivated (FI-RSV) vaccine were halted when more vaccinated children were hospitalized after RSV infection compared to those who were not vaccinated. Since then, no RSV vaccine has been approved.

"An effective RSV vaccine must protect against infection without priming the host for excessive inflammation," says Jeff Powell, Ph.D., Vice President of Immunology at ACT. 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.

When tested in mice, the results of the modified vaccine were remarkable. Compared to the original version, it produced a more powerful immune response (revealed by antibody testing), lowered lung inflammation (as measured by white blood cells called eosinophils), and offered protection from RSV infection at a dose 30 times lower than the original vaccine.

"We showed that, with a very simple modification, we were able to guide the immune system's response to our vaccine," says Powell.

HOW IT WORKS
Two major proteins on the surface of the RSV virus are involved in infection: the attachment G protein (which attaches to a human cell) and the fusion F protein (which opens up and delivers the viral payload). Infection is prevented if either of these proteins is blocked by a vaccine-induced immune response. ACT's microparticle vaccine carries a synthetic antigen of the G protein to elicit host antibodies that block viral attachment to host target cells. (Other RSV vaccines in late stage development are focused on the viral F protein.) While this adaptive (virus-specific) immune response is sufficient to reduce viral infection, the innate (non-specific) immune response may still trigger inflammatory Th2-type mechanisms that are thought to be partly responsible for the VERD in vaccinated children in the 1960s.

Powell and his colleagues sought to increase the potency of their G-protein vaccine while also reducing the potentially harmful Th2-type inflammatory response. To do this, they added a TLR2 ligand to the vaccine to properly engage the innate response and redirect the adaptive response away from Th2-type and toward the less inflammatory Th1-type. To test their hypothesis that the modified microparticle would protect the host from both infection and excess inflammation, the ACT team vaccinated mice with one of two microparticle candidates (one with the TLR2 ligand and one without), then infected the mice with RSV.

Mice that received the modified vaccine exhibited significantly higher levels of G-specific antibodies; complete protection from viral infection at a 30-fold lower dose than the original unmodified vaccine; a shift in the lung cytokine/chemokine content from an inflammatory Th2 profile to a protective Th1 profile; and significant reduction 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," says Powell. "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."

ACT's collaborative study with Dr. Ralph Tripp of the University of Georgia College of Veterinary Medicine was funded by a grant from the National Institutes of Allergy and Infectious Diseases (1R43AI092924-01) awarded to ACT. The paper can be found in Volume 10, Issue 12 of the journal Vaccines

ARTIFICIAL CELL TECHNOLOGIES: INNOVATIVE VACCINE DESIGN
Artificial Cell Technologies, Inc. is a development-stage biotechnology company designing fully synthetic vaccines with a proprietary Layer-by-Layer (LbL) technology of ultra-thin polypeptide nanofilms deposited on a calcium carbonate core. The totally synthetic manufacturing platform does not utilize any biological production systems, thus reducing the chances of contaminants and simplifying production. ACT's efficient technology allows scientists to rapidly design, modify, and manufacture vaccines in a fraction of the space and time required by more traditional 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."

In addition to the RSV vaccine candidate, the company's product pipeline also includes a vaccine candidate for malaria that has recently completed Phase 1a clinical evaluation, demonstrating safety and immunogenicity of the platform in adult human volunteers. ACT is currently preparing for a Phase 1b controlled human malaria infection (CHMI) clinical trial of its malaria vaccine.

ACT's headquarters and laboratory facilities are located in New Haven, Connecticut. For more information, please visit our website at https://artificialcelltech.com/

SOURCE Artificial Cell Tech Inc