Adjuvanted liposomal vaccine protects baby mice from RSV, looks promising for human newborns

By Nick Paul Taylor, The Science Advisory Board contributing writer

August 3, 2022 -- After a more than 50-year wait, a vaccine to protect infants from respiratory syncytial virus (RSV) -- the leading global cause of death in children under age five -- could finally become a reality. A single dose of an adjuvanted liposomal vaccine formulation has induced protection against RSV infection in baby mice.

Writing in an August 2 article in Nature Communications, researchers at Boston Children's Hospital describe the use of two adjuvants that stimulate the TLR7/8 and Mincle receptors in combination with a RSV protein to protect newborn mice from a direct challenge with the respiratory pathogen.

The researchers are now working to optimize the RSV formulation and study it in larger animals with a view to running trials in humans and applying the technology to other intracellular pathogens such as influenza and coronaviruses.

Multiple companies are working on ways to protect babies from RSV, with Pfizer aiming to provide protection by vaccinating pregnant women and AstraZeneca and Sanofi planning to give a long-acting antibody to infants before their first RSV season. However, none of the approaches in advanced clinical development provide direct vaccination of babies.

Researchers have been wary of vaccinating babies against RSV since a study in the 1960s, in which a Th2 white blood cell response in infants' airways caused respiratory distress and deaths. The discovery of the neonatal bias towards Th2-mediated immunity spurred interest in ways to induce Th1 immunity. In 2016, researchers found stimulating the TLR7/8 and Mincle receptors with adjuvants activated Th1 responses, leading to yesterday's publication.

In the new study, the researchers packaged the TLR7/8-Mincle adjuvants and the RSV pre-F antigen in a liposomal formulation, called CAF08. The formulation induced strongly neutralizing antibodies and Th1 and CD8-positive T cell responses and, in doing so, protected the baby mice against RSV.

Administered to cultured antigen-presenting cells from donated cord blood from human newborns, the formulation enhanced the production of cytokines by Th1 cells. Applied to blood cells from adult mice and humans, the vaccine formulation did not induce the same protective Th1 immune responses.

"The combination is most active in early life," Dr. Ofer Levy, PhD, the study's senior investigator and a professor of pediatrics at Harvard Medical School, said in a statement. "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 next step is to prepare the vaccine formulation for study in larger animals. If the candidate impresses in those tests, it could move into clinical trials and ultimately potentially provide a way to directly protect babies from RSV.

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