Respiratory syncytial virus (RSV) is the biggest global cause of death in children under the age of five, and there is no effective vaccination.

In a study from the Precision Vaccines Program at Boston Children’s Hospital, a novel vaccine formulation prevented infection in newborn mice and stimulated potent immune responses in laboratory immune cells from human newborns.

Results were published in Nature Communication today.

RSV is a primary cause of infant hospitalizations in the United States and also poses a risk to older adults. While multiple prospective RSV vaccinations are in late-stage clinical trials in adults, no such vaccines for children have been developed since the catastrophic failure of a candidate vaccine in 1966.

The vaccine instead led to an allergic-like (“Th2”) white blood cell response in the infants’ airways because the antibodies it produced were unable to kill the virus. When vaccinated infants contracted RSV, they experienced respiratory distress, which made them sicker and led to some deaths.

“Consequently, pediatric vaccine development was halted, recognizing that the immune system in kids is different from that in adults,” remarks Simon van Haren, first author of the new paper.

New RSV vaccine

Van Haren, Ofer Levy, MD, PhD, who oversees the Precision Vaccine Program, and his associates made the decision to revisit the investigation and look at further ways that immunization could boost the immune system of a newborn without causing damage. They looked at various immune cell receptors and various adjuvant vaccine combinations (components added to boost the immunological response) that might activate these receptors and increase the effectiveness of immunization.

In the Journal of Immunology, scientists reported in 2016 that the combination of two possible adjuvants, activating the TLR7/8 and Mincle receptors, elicited strong responses in babies’ antigen-presenting cells, which are crucial for initiating cellular immunological defenses.

They observed substantial type 1 T-helper (“Th1”) response activation. The ineffective RSV vaccine failed to elicit a Th1 response, which is necessary for a potent defense against viral infections but difficult to trigger in infants.)

At the Statens Serum Institut in Copenhagen, Denmark, van Haren and Levy collaborated with Dennis Christensen, PhD, and Gabriel Pedersen, PhD, to create a brand-new protein-based RSV vaccine.

This vaccine used the same adjuvant combination that was reported in 2016. It was called CAF-08, and it was mixed with a protein from RSV and put inside fatty particles called liposomes.

First, the scientists injected cultured antigen-presenting cells made from donated cord blood from newborn humans with the CAF-08/RSV vaccination.

The team at Boston Children’s, led by Dr. Hanno Steen, used phosphoproteomics to thoroughly profile the cell responses. This demonstrated increased cytokine (signaling molecule) synthesis by Th1 cells as well as other signs of a potent immune response.

“Dr. Steen’s group was instrumental in helping us define the mechanism of action of our adjuvant combination, and why it works so well in children and less so in adults,” adds van Haren. “It lays out the molecular requirements for an adjuvanted vaccine to work in early life.”

They then tested CAF-08/RSV in newborn mice and discovered that it provided protection from an RSV direct challenge with no signs of animal injury. Additional research revealed that it stimulated Th1 cells, CD8+ T cells (also crucial for cellular immune responses), and neutralised antibodies that specifically recognized RSV.

“The undesirable components of the immune response did not come into play,” adds van Haren.

It is important to note that this particular vaccine formulation did not elicit the same protective Th1 immune responses in the blood cells of adult humans or adult mice.

According to Levy, the senior scientist on the study, “the combination is most active in early life.

“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.”

Now that the RSV vaccine formulation has been improved, Levy and van Haren intend to test it in larger animal models and eventually put it through clinical trials.

Image Credit: Getty

You were reading: RSV: New Vaccine Evokes Strong Immune Response Against Dangerous Infection