Respiratory syncytial virus (RSV) is a major cause of infant hospitalization and a leading cause of death around the world for children under age 5. It's also a danger to older people. There are adult vaccines for RSV in trial, and now, there is an RSV vaccine candidate for children. New research has shown that a trial vaccine caused a significant immune response in cells obtained from newborn infants, and prevented RSV infection in newborn mice. The findings have been reported in Nature Communications.
In 1966, an RSV vaccine for children failed in trials. Instead of neutralizing the virus, antibodies that were produced because of the vaccine caused a reaction similar to an allergy in infant airways. If vaccinated infants were then infected with RSV, serious respiratory problems ensued, and caused the illness to get worse. Some children died.
"Consequently, pediatric vaccine development was halted, recognizing that the immune system in kids is different from that in adults," noted first study author Simon van Haren, Ph.D., an immunologist in the Precision Vaccines Program at Boston Children's Hospital.
Van Haren and colleagues decided to tackle the problem, and assessed different ways to improve the formulation, including alternative adjuvants, which are used in vaccines to boost the immune response, and various immune receptors. Adjuvants that acted on TLR7/8 and Mincle receptors were identified in 2016 by the research team; the adjuvant combination induced the right response in immune cells.
In this study, the adjuvant combination, called CAF-08, was targeted again and used as part of a protein-based RSV vaccine. The combo was packed into liposomes. This novel RSV vaccine was then tested on cells isolated from donated cord blood from newborn infants.
The researchers used a tool called phosphoproteomics to characterize how the cells reacted to the vaccine. This showed that cytokines were generated by type 1 T helper (Th1) cells, an important factor in fighting viruses that showed the immune response was robust.
When the CAF-08 RSV vaccine was tested in newborn mice, they remained healthy when exposed to RSV. There was no evidence of an adverse response. The vaccine was shown to trigger the production of neutralizing antibodies, activate Th1 cells, and CD8+ T cells that recognized and reacted to RSV.
"The undesirable components of the immune response did not come into play," added van Haren.
The vaccine did not seem to be effective in adult humans.
"The combination is most active in early life," said senior study investigator Ofer Levy, MD, Ph.D., who directs the Precision Vaccine Program. "We hope this adjuvant combination, tailored to be effective in early life, will eventually enable the vaccination of infants against not only RSV, but also influenza, coronaviruses, and other serious infections."
The researchers are now working to plan clinical trials.
