Insights for Developing RSV Vaccines

Synagis needs to provide both the antiviral activity and a countermeasure to the viral distortion of the host immune response

In healthy adults Respiratory Syncytial Virus (RSV), feels like the common cold, however, it is a very serious condition for infants. 

Contracting RSV within the first few months of life can make a child more susceptible to developing asthma later in life. 

In fact, nearly 40 percent of infants who contract RSV develop severe bronchiolitis or pneumonia, with 1 to 3 percent hospitalized. 

“Since there are currently no effective RSV vaccines available, infants are essentially defenseless against this common virus," Stephania Cormier, Ph.D., the LSU Department of Biological Sciences Wiener Chair professor, said in a press release.   

A new publication by Dr. Cormier and colleagues offers new insights for RSV vaccine development, both active and passive, to prevent this deadly disease. 

This new study is of particular interest following the recent failure of ResVax, an RSV vaccine by Novavax, to prevent RSV disease in infants via maternal immunization. 

"Because an infant's immune system develops gradually within the first 6 months of life, the immune system does not respond and fight back in the same way as an adult would when infected by RSV,” said Dr. Cormier. 

The paper reviews the existing data demonstrating the importance of a family of small proteins called type 1 interferons, which are released by cells in response to viruses and are key to the body's immune response. 

For example, when an infant is exposed to the influenza virus, its body launches an interferon response that fights back against the virus. 

However, infants who develop severe RSV bronchiolitis or pneumonia do not launch an interferon response when exposed to RSV. The scientists urge pharmaceutical companies to consider strategies for enhancing type 1 interferon responses to aid in combating RSV in infants. 

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"Vaccine developers need to look at how infants are responding immunologically to a vaccine at the site of infection. Our research shows that simply increasing circulating neutralizing antibodies is not enough to prevent disease in infants; it is also important to induce type 1 interferons," Dr. Cormier said. 

She suggests approaches to restore a normal interferon response to a vaccine, which enhances the body's immune response providing protection from disease. 

Since the development of active vaccines is a long and costly endeavor, pharmaceutical companies are also interested in passively administering antibodies manufactured in the lab. 

For the past 20 years, the leading medication of this type called Synagis has been used to reduce disease severity in the high-risk population of premature birth infants. 

The new understanding of the host immune response to RSV suggests that improvements on Synagis need to provide both the antiviral activity and a countermeasure to the viral distortion of the host immune response. 

"Because Synagis has been a useful drug, most pharmaceutical efforts have targeted the same viral protein, called the F protein, as this approved drug.” 

“However, a different viral protein, called the G protein, has been implicated as a key driver of the immune system's weak response. Antibodies against the G protein provide an antiviral activity that is as good as those targeting the F protein, while also normalizing the host immune response," said co-author Lawrence Kauvar, chief scientific officer of Trellis Bioscience, which is close to being ready to begin testing an antibody against the G protein in human clinical trials. 

In developing a new RSV vaccine for infants, the scientists urge the vaccine developers to think outside of the box. 

"If we can unlock infants' type 1 interferon response, it could potentially change vaccines for all infants. It's exciting," Dr. Cormier said.