A unique adjuvant can prevent vaccine-enhanced respiratory disease, a sickness that has posed a major hurdle in vaccine development for RSV, according to a study with mice.
An adjuvant is a substance that enhances the body’s immune response to toxins and foreign matter.
The study suggests that combining this adjuvant, which researchers at the Institute for Biomedical Sciences at Georgia State University created, with RSV (respiratory syncytial virus) vaccination might prime the body for protective immune responses and prevent inflammatory RSV disease after infection.
The findings, published in the journal Virology, could lead to advances in RSV vaccine development.
RSV, a common respiratory virus that causes cold-like symptoms, is the leading cause of serious respiratory diseases such as bronchiolitis and pneumonia in children under 1 in the United States. Each year in the US, an estimated 57,000 children younger than 5 years old are hospitalized with an RSV infection. RSV is also a significant cause of respiratory illness in older adults, resulting in 177,000 hospitalizations and 14,000 deaths each year, according to the Centers for Disease Control and Prevention. There is no vaccine to prevent RSV.
Progress on a vaccine for RSV almost ceased in the 1960s after a formalin-inactivated RSV vaccine being tested in the US not only failed to protect children, but also resulted in many infants experiencing worse symptoms than usual, requiring hospitalization after natural infection with the virus. Two toddlers died from enhanced disease symptoms. Other RSV vaccines have been known to cause enhanced disease after RSV infection.
The new study investigated the effects of a unique adjuvant on vaccine-enhanced respiratory disease after infant and adult mice were vaccinated against RSV and exposed to the virus. The adjuvant was created by combining pathogen-recognizing receptor agonist adjuvants monophosphoryl lipid A (MPL) and oligodeoxynucleotide CpG (CpG), which are known to activate innate immune responses.
Researchers injected infant and adult mice with either RSV fusion proteins only, RSV fusion proteins plus adjuvant, or a control phosphate buffered saline solution. Blood samples were taken after three weeks. Four weeks after vaccination, mice were intranasally infected with RSV and samples were taken to determine the efficacy of protection.
The adjuvant was found to be effective in promoting the induction of protective antibodies, clearing the lungs of the virus after exposure to RSV, and avoiding disease in lung tissue.
“RSV subunit vaccination adjuvanted with a unique combination pathogen-recognizing receptor agonist might provide protection against RSV, preventing inflammatory RSV disease after infection. However, its efficacy in larger animal models and in humans remains unknown,” says Sang-Moo Kang, lead author and a professor in the Institute for Biomedical Sciences at Georgia State.
Coauthors of the study are from the Vaccine Research Center at the National Institutes of Health’s National Institute of Allergy and Infectious Diseases and the Institute for Biomedical Sciences at Georgia State.
The National Institutes of Health’s National Institute of Allergy and Infectious Diseases funded the work.
In another recent study, published in the journal Antiviral Research, Kang found that an inactivated split RSV vaccine with a unique combination adjuvant was more effective in increasing immune responses and antibodies, lung viral clearance, and preventing pulmonary tissue disease than an earlier form of the vaccine. Mice received the vaccine with and without the adjuvant and then infected with RSV. The study found the split RSV vaccine could be a viable vaccine candidate when combined with the immune modulating vaccine adjuvant.
Source: Georgia State University
