New vaccine formulation protects newborn mice against respiratory syncytial virus (RSV)

Transmission electron micrograph of RSV. Credit: CDC/Dr. Erskine Palmer / Public Domain

Respiratory syncytial virus (RSV) is the world’s leading cause of death in children under the age of 5 and who are immunocompromised. In a study from the Immunization Program at Boston Children’s Hospital, a new vaccine protected newborn mice from infection and elicited strong immune responses from human infants in laboratory. Results were reported on August 2 Nature communication.

RSV is the leading cause of hospitalization in the United States and is a threat in the United States big big. While several potential RSV vaccines are in late-stage clinical trials in adults, there is no such vaccine for children since major candidate failures. prevention in 1966. The antibodies produced by this vaccine were unable to eliminate the virus; instead, the drug induced an allergic-like (“Th2”) white blood cell response in the infants’ airways. This caused respiratory distress when vaccinated infants become infected with RSV—making them sick and causing death.

“Therefore, the development of childhood vaccines has been stopped, knowing that immune system in children is different than in adults,” said Simon van Haren, Ph.D., immunologist in Vaccine Programs and first author on the new paper.

Rethink the RSV vaccine

Van Haren, Ofer Levy, M.D., Ph.D., who directs the Adaptive Marketing Program, and their collaborators decided to reopen the case and identify other ways in which the vaccine can stimulate the immune system of infants. without causing harm. They researched different receivers on Antibiotics and different combinations of antibiotics (foods added to stimulate the immune response) that can stimulate these receptors, making antibiotics more effective.

In 2016, they he reported in Journal of Immunology that the combination of two potential adjuvants, stimulators of TLR7/8 and Mincle receptors, induced a strong response in the antigen-presenting cells of infants, important for the induction of cellular immunity. They saw the ability to activate type 1 T-helper (“Th1”) responses. These Th1 responses are difficult to stimulate in infants, but a strong defense against pathogens is required; (A failed RSV vaccine did not induce a Th1 response.)

For the new project, van Haren and Levy teamed up with Dennis Christensen, Ph.D., and Gabriel Pedersen, Ph.D. at the Statens Serum Institute in Copenhagen, Denmark, to create a new protein-based RSV vaccine. This vaccine uses the combination of an adjuvant reported in 2016, which they named CAF-08, with a protein from RSV and packaged in lipid molecules called liposomes.

The team first administered the CAF-08/RSV vaccine to antigen-presenting cells obtained from cord blood donations from human infants. Led by Hanno Steen, Ph.D., at Boston Children’s, the researchers detailed the cells’ response with phosphoproteomics. This explains the increased production of cytokines (signaling cells) by Th1 cells and other markers of a strong immune response.

“Dr. Steen’s team helped us to explain our collaborative approach, and why it works so well in children and less so in adults,” said van Haren. “It lays out the genetic requirements for the vaccine to work on the beginning of life.”

They later tested CAF-08/RSV in newborn mice and found that it protected against direct challenge with RSV, with no evidence of any disease in the animals. Further studies have shown that it induces Th1 and CD8+ T cells (also important in triggering an immune response) that specifically recognize RSV, and eliminate the virus.

“Things I don’t like immune response I didn’t come into play,” said van Haren.

Notably, this vaccine regimen did not induce the same Th1 immune response in the blood The cells from either adults or adults.

“The connection is more active early in life,” said Levy, the study’s lead researcher. “We hope that this combination, designed to be effective early in life, will allow babies to be immunized not only against RSV, but also against influenza, coronaviruses, and other serious diseases.”

Levy and van Haren now plan to adapt the RSV vaccine and test it in larger animal models, with the goal of bringing it into clinical trials.

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Additional information:
Nature communication (2022). DOI: 10.1038/s41467-022-31709-2

hintNew vaccine protects newborn mice from respiratory syncytial virus (RSV) infection (2022, August 2) Retrieved August 2, 2022 from newborn-mice-respiratory-syncytial.html

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New vaccine formulation protects newborn mice against respiratory syncytial virus (RSV) Source link New vaccine formulation protects newborn mice against respiratory syncytial virus (RSV)

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