Many vaccines are only partially effectivethey have an efficacy ebb either No They work well in very young or very old. For more than a decade, Dr. Offer Levy and Dr. David Dowling, of the Precision Vaccines Program of the Boston Children’s Hospital (USA), have tried to improve vaccines by adding compounds known as Adjuvantes to reinforce the immune responses of the vaccine receptors.
In depth
Now, within the framework of an important contract of the adjuvant discovery program of the National Institute of Allergies and Infectious Diseases (Niaid, by SIS acronym in English), have identified a new and promising own adjuvant, called PVP-037. The finding is published in ‘Science Advances‘.
“In principle, this compound can Add to any vaccine to enhance your action“says Levy, who directs the precision vaccine program.” Adjuvants are like rocket fuel for the immune system. PVP-037 is one of the adjuvants more active that we have discovered and we believe that induces a larger, more durable and broader immune response to vaccines“
The researchers began by analyzing More than 200,000 small molecules of a library of Harvard’s Faculty of Medicine in human immune cells, specifically, in mononuclear cells of primary peripheral blood, obtained from donors and cultivated in their own plasma using a method developed within the precision vaccine program. This threw around 25 confirmed results, being PVP-037 the most active.
More details
He PVP-037 It belongs to a family of molecules called imidazopyimidines, which according to the study are active immunomodulators. He PVP-037 and its analogues They act on the innate immune system, stimulating patterns recognition receptors TLR7 and TLR8 In antigens presenting cells, such as monocytes and dendritic cells.
“The analysis of small molecules in primary human cells is more complicated than the use of a homogeneous cell line, because each individual is different“, clarifies Levy.” But that’s the aim: Better reflect human biology. A good adjuvant should be able to function in diverse populations. The PVP-037 would not have been discovered through the analysis of cell culture lines. “
An optimized version of PVP-037 demonstrated broad innate immune activation in the donor’s immune cells, inducing NF-? B and the production of TNF and other cytokines, signaling molecules that GThey will be a broader immune response. It should be noted that PVP-037 did not cause this response in cultivated cell lines. In live mice, It improved the antibody responses against the proteins of the influenza and SARS-COV-2 vaccine.
To take into account
What most excites Levy and Dowling It is that, in addition to inducing a robust immune activity, the compound is stable, easy to work and lends itself to chemical optimization for medical use. It can be formulated in most Standard use drug administration systems, such as AGU oil emulsionsto.
“With the discovery of PVP-037 we did something special“, Corrobora Dowling.” Our work basically condensed the entire vaccine development process, including analogous optimization, the establishment of the mechanism of action and the creation of a Optimized Formula “.
Boston Children’s has multiple patents about these discoveries, with Levy and Dowling as named inventors. With the support of the Niaid, plan to evaluate PVP-037 in all age groups and prove their capacity To improve immune responses to influenza vaccines and whore cough, as well as an opioid vaccine aimed at preventing fentanyl overdose deaths. Patents also cover potential uses of imidazopyimidines such as immunomodulatory compounds for allergy and cancer, future additional research lines. “In general, we hope that our precision vaccine approach Inspire others to adopt a similar innovation strategy for the discovery and development of adjuvants and vaccines“Dowling ends.
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