For a vaccine to be most effective, sometimes nature needs a little 'extra' something. That something is often an adjuvant -- small molecules added to a vaccine that boost the body's immune response. For years, the Precision Vaccine Program (PVP) at Boston Children's Hospital has been a leader in adjuvant discovery and developing new ways to study how human cells respond to vaccination outside of the body, known as in vitro testing.
In order to advance this work, the PVP was awarded with a $1 million, two-year grant from the Bill & Melinda Gates Foundation, to extend its research into adjuvant-based vaccines. The grant provides funds for PVP to assess between six to eight adjuvants currently managed by the Vaccine Formulation Institute (VFI).
Establishing the activity of several adjuvant formulations from VFI in human in vitro platforms in the PVP will be a major step towards global access of important adjuvant formulations."
Simon van Haren, Ph.D., Project Leader, PVP
Provides access to privately owned adjuvants and vaccine formulations
Many current vaccine adjuvants and vaccine formulations are protected by patents and other intellectual property. VFI was created by the World Health Organization as a way to increase access to important adjuvants and vaccine formulations that are not available to vaccine research groups. With the grant, PVP will be able to test several adjuvants in a set of formulations that are available only through VFI.
In many vaccines, the adjuvant that activates the human immune system is packed inside of a unique delivery molecule. "It is called a formulation meaning it contains a mixture of different molecules designed to enhance the immune system's response and minimize side effects," says van Haren. The PVP will study the extent to which these formulations switch on the immune system, regardless of any specific pathogen.
Studying vulnerable patient groups
VFI will create several vaccine formulations that PVP will test in its research platform designed to mimic the actions of human cells. They will test the various formulations in cells from different patient populations, including newborns, children, adults, and the elderly. This precision vaccines approach to vaccine development is a key strength of PVP's research -- to design vaccines optimized for vulnerable populations.
"Because the immune system responds to different molecules according to age, one of our goals is to compare adjuvants in cells from different age groups," says van Haren. Their goal is to see if they can determine which molecules or formulations work best in the different age groups.
Unique vaccine formulations
PVP will gain access to several types of unique adjuvant delivery vehicles. The adjuvant under study will be loaded into the carrier molecules, either a liposome or an oil and water emulsion. Liposomes are small lipid compounds and are the most common type of adjuvant carrier.
These delivery vehicles are packed with an adjuvant. Some of the key adjuvants PVP will study are molecules that stimulate toll-like receptors, including toll-like receptor 4, 7, or 8. Toll-like receptors are well known to trigger the innate immune responses and enhance a potential protective immune response induced by vaccines. Responses to toll-like receptor stimulants also vary by age.
"Depending on the delivery vehicle, that can also influence how effective the vaccine formulations are or how well they work in children or in adults," says van Haren.