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In a new study, researchers from Boston Children’s Hospital study responses to pneumococcal vaccine in infant monkeys.
Researchers at Boston Children’s Hospital report achieving strong vaccine responses in newborn animals, including monkeys-the final preclinical model before human trials- by adding compounds known as adjuvants that boost the immune response. The new studies, announced on April 5, 2017 and led by David Dowling, PhD, are aimed at tailoring vaccines to newborns’ unique immune systems. Results from the studies were recently published in the Journal of Clinical Investigation-Insight (JCI-Insight) and the Journal of Allergy and Clinical Immunology (JACI).
According to a statement from 3M, the pneumococcal vaccine was used as a test case because it can cause potentially fatal pneumonia, meningitis, and sepsis in infants. In the first study (JCI-Insight), newborn Rhesus monkeys were given a series of three shots with the existing Prevnar 13 (Pneumococcal 13-valent conjugate vaccine [Diphtheria CRM197 protein]) pneumococcal vaccine. This vaccine is already packaged with an adjuvant (Alum), and half the monkeys were randomized to also receive a toll-like receptor (TLR)-7 and TLR-8 agonist adjuvant called 3M-052. Blood was drawn at different time points to see how well the immune system was activated.
When compared with treatment with Prevnar 13 alone, monkeys treated with 3M-052 produced a more robust antibody response (antibody levels were 10 to 100 times greater) at a faster rate-high enough to ensure protection against infection. The 3M-052 treatment group also showed enhanced CD4+ T cells and B cells specific to Streptococcus pneumoniae.
The adjuvant works by stimulating a set of receptors on white blood cells known as Toll-like receptors. Research has found that stimulating two of these receptors, TLR-7 and TLR-8, induces the strongest antibody response. Studying white blood cells derived from newborn animals’ umbilical cords, the researchers also saw robust T helper 1-cytokine production when given 3M-052 alone. When the adjuvant from 3M was added to Prevnar 13, the immune response was synergistic.
“This study shows that the Toll-like receptor 7/8 agonist 3M-052 enhance neonatal primate immune responses to pneumococcal conjugate vaccine more effectively than Alum,” said Dr. Mark Tomai, head of 3M TLR and microstructured transdermal systems (MTS) business development. “Many adjuvants are not very effective in newborns. The fact that 3M-052 was very effective in newborn monkeys shows the potential for using this adjuvant in immunizing the very young.”
The 3M-052 adjuvant used for this monkey study is designed to minimize side effects; it is configured chemically with a lipid tail that mixes poorly with water, making it insoluble in aqueous formulations. This configuration keeps it from getting into the bloodstream, where it could cause inflammation and flu-like symptoms. The research team’s next steps are to develop a highly stable formulation, obtain more safety data and further characterize age-specific responses, comparing newborns versus older infants in animal studies.