Researchers from Boston Children’s Hospital said today that they achieved strong vaccine responses in preclinical models by adding adjuvants to boost the immune response. The team’s work was published the Journal of Clinical Investigation-Insight and the Journal of Allergy and Clinical Immunology.
Vaccines have the potential to drastically reduce infant mortality, the researchers said, but newborns often don’t respond optimally because their immune systems produce weak antibody responses. The team wrote that their work could potentially help amplify newborns’ immune response to vaccinations.
“Our efforts to understand the biology of the newborn immune system has now led to adjuvant approaches that may enable earlier protection of newborns and young infants from life-threatening infectious diseases, such as pneumococcus, pertussis or even respiratory syncytial virus (RSV),” senior investigator Ofer Levy said in prepared remarks.
In the 1st study, researchers gave newborn Rhesus monkeys 3 shots with the existing pneomococcal vaccine, which is already made with an adjuvant. Half of the monkeys were randomized to receive an additional adjuvant, known as 3M-052, which has been shown to activate newborn immune response.
After 28 days, the animals that were dosed with 3M-052 were much quicker to mount a strong antibody response compared to their counterparts.
“The protective antibody response we saw was so strong that it’s conceivable that you could get protection with 1 shot,” Levy explained. “This is critical because in many parts of the world, birth is the most reliable point of healthcare contact. After birth, it becomes challenging to bring children in for repeated clinic visits.”
The 3M-052 compound stimulates a set of receptors found on white blood cells called Toll-like receptors. Levy’s lab has shown that stimulating 2 of these receptors triggers a strong antibody response.
The 3M0052 adjuvant was manufactured by 3M Drug Delivery Systems, which helped to fund the study, and was designed with a lipid “tail” that does not mix well with water. This feature keeps it from infiltrating the bloodstream, according to the team.
“Rather than floating all over the place causing fever and chills, when you inject this 3M-052 adjuvant, it stays put in the muscle and enhances the immune response to the vaccine,” Levy said.
In the 2nd study, researchers encapsulated the vaccine antigen and an adjuvant called CL075 in nanoparticles that were engineered to be taken up by antigen-presenting cells.
The nanoparticles triggered immune responses when added to human cells and injected into mice, the team reported, and the response was better than those induced by the vaccine alone.
The researchers hope to develop a stable formulation and obtain more safety data, as well as compare newborns’ responses to older infants.
“There’s not a long list of vaccines that can be given at birth and we need better vaccine formulations against a range of early life infectious pathogens,” Levy said. “We hope to meet these challenges.”
