Vaccination to reduce infant mortality

Published: 6-Apr-2017

New study shows 3M adjuvant boosts immune response and potentially reduces side effects

Protecting newborns and young infants from life-threatening infectious diseases, such as pneumococcus or pertussis, is a complex challenge.

Their unique immune systems typically mount weak antibody responses to most vaccines, leaving them highly vulnerable to potentially fatal illnesses.

Now, researchers at Boston Children’s Hospital report achieving strong vaccine responses in newborn animals by adding adjuvants – compounds that boost the immune response.

The new studies, led by David Dowling, cap a decade of research in the laboratory of Ofer Levy, aimed at tailoring vaccines to newborns’ unique immune systems.

Pneumococcal vaccine was used because it can cause potentially fatal pneumonia, meningitis, and sepsis in infants.

It’s conceivable that you could get protection with one shot.

In the first study, Newborn Rhesus monkeys were given a series of three shots with the existing Prevnar 13 pneumococcal vaccine.

This vaccine is already packaged with an adjuvant (Alum) but half the monkeys were randomised to also receive a toll-like receptor agonist adjuvant called 3M-052.

At day 28, the animals were much quicker to develop an antibody response.

Moreover, their antibody levels were 10–100 times greater than that with Prevnar 13 alone — high enough to ensure protection against infection.

“The protective antibody response we saw was so strong that it’s conceivable that you could get protection with one shot,” said Levy.

“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 adjuvant works by stimulating a set of receptors on white blood cells, known as Toll-like receptors, to induce a strong 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 it was added to Prevnar 13, the response was synergistic.

We need better vaccine formulations against a range of early life infectious pathogens.

Mark Tomai, head of 3M TLR and Microstructured Transdermal Systems (MTS) Business Development, said:

“Many adjuvants are not very effective in newborns. The fact that 3M-052 was effective in newborn monkeys shows the potential for using this adjuvant in immunising the young.”

The 3M-052 adjuvant is designed to minimise side effects; it is configured chemically with a lipid “tail” that mixes poorly with water which makes it insoluble in aqueous formulations.

This configuration keeps it from getting into the bloodstream, where it could cause inflammation and flu-like symptoms.

“Rather than distributing throughout the body, when you inject the 3M-052 adjuvant, it is retained at the injection site in the muscle and enhances the immune response to the vaccine,” said Levy.

He plans to work with collaborators to work towards eventual human trials.

“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.

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