The effectiveness of vaccines can be significantly increased, by more than 25%, if chiral gold nanoparticles, oriented to the left, are added as adjuvants. The discovery was made through international collaboration with the participation of Brazilian researchers. Article about it has just been published in the magazine Nature.
The study brought together research groups from the universities of Michigan, in the United States, and Jiangnan, in China. The Brazilian participation was led by André Farias de Moura, professor at the Department of Chemistry at the Federal University of São Carlos (UFSCar) and researcher at the Center for the Development of Functional Materials (CDMF), one of the Research, Innovation and Dissemination Centers (Cepids) from Fapesp.
The investigation also received funding from Fapesp through research grants granted to Moura.
response enhancer
The work was not carried out with vaccines against covid-19, because it began to be done well before the current pandemic. The researchers used vaccines developed for a strain of influenza virus, which is also not the one currently circulating in Brazil. But the results can, in principle, be generalized to any type of vaccine – with complementary studies on a case-by-case basis, of course. This is because the left-oriented chiral gold nanoparticle is not the active ingredient of the vaccine, but an adjuvant that enhances the immune system’s response to the immunizer.
“The key to understanding the contribution of these nanoparticles is the concept of chirality, which applies to an object or system that cannot be superimposed on its mirror image,” Moura tells Agência Fapesp.
The term derives from the Greek word kheir, which means hand. And the quintessential example of chirality is exactly given by our right and left hands. When we look in the mirror with both hands flat in front of us, the hand we see on the right of the image is our left hand. And vice versa.
“Everything that is alive on planet Earth is chiral. Chiral molecules can have completely different properties, whether they are oriented to the left or to the right. The two chiral forms of the same molecule are called enantiômeros. A tragic example was thalidomide, a drug produced to treat nausea during pregnancy that, in the 1960s, caused a worldwide outbreak of fetal malformations. Because, while one of the enantiomers of the substance had the expected therapeutic effect, the other caused atrophy in the limbs of the baby that was being gestated”, says Moura.
how it was done
The researcher reports that, at the current stage of the study of nanomaterials, it is possible to completely separate one enantiomer from the other. And the study in question was based precisely on this possibility. “We started with gold nanoparticles, which, because they are symmetrical, do not present chirality. They are achiral. And we induced chirality in them, making them interact first with the amino acid cysteine ??and, in the next step, further intensifying the chirality induced by exposing the nanoparticles to polarized light, using the amino acid phenylalanine as an antenna to tune the light”, he reports.
Chirality is measured by the so-called “g factor”, on a scale that goes from negative two (-2) to plus two (+2). The procedure allowed to reach a value of g greater than 0.4. This resulted in three types of nanoparticles: the original, achiral gold; the right enantiomer; and the left enantiomer.
“Initially, we tested the nanoparticles in cultures in vitro of cells of the human immune system. And we found that chiral nanoparticles induced the production of substances associated with the immune response even in the absence of antigens, that is, of something capable of producing antibodies. This type of reaction is exactly what the adjuvant does in a vaccine”, says Moura.
available knowledge
Then the team tested the nanoparticles on a strain of influenza. “We found that the enantiomers caused the applied vaccine to have a very large increase in effectiveness. Specifically, the left enantiomer caused an increase in efficiency of 25.8%, compared to the right enantiomer, and even greater in relation to the achiral nanoparticle”, adds Moura.
The researcher emphasizes that the knowledge is published and available to anyone who wants to use it. “Any manufacturer of any type of vaccine, including for new variants of the coronavirus or influenza, will be able to make use of it. We are not vaccine developers, but we are offering basic knowledge, a new technological platform, for those who develop”, he concludes.
The article Enantiomer-dependent immunological response to chiral nanoparticles can be read at: www.nature.com/articles/s41586-021-04243-2.