Researchers have developed a new nanoparticle adjuvant. Experiments in mice have shown that it improves antibody production after vaccinations against HIV, diphtheria and influenza.

To improve the effectiveness of vaccines, adjuvants are often used – compounds that stimulate the immune system to a stronger response. Although the very idea of ​​using adjuvants has been around for a long time, the FDA has approved only a few options. One is aluminum hydroxide (an aluminum salt that causes inflammation) and the other is an oil-in-water emulsion used in influenza vaccines.

Several years ago, the FDA approved a saponin-based adjuvant, a compound derived from quillaya soap bark. Saponin is used as an adjuvant in the shingles vaccine. Saponins in the form of nanoparticles that resemble a cell (the so-called immunostimulating complex, ISCOM) have also found use in a vaccine against COVID-19, which is undergoing clinical trials.

Researchers have shown that saponins promote inflammatory immune responses and stimulate antibody production, but it is unclear how they do this. In a new study, the MIT team wanted to find out how an adjuvant works and if they could make it stronger.

They have developed a new type of adjuvant that is similar to ISCOM but also includes a molecule called MPLA, a toll-like receptor (TLR) agonist. When MPLA binds to toll-like receptors in immune cells, they induce inflammation. The researchers call their new adjuvant SMNP (saponin / MPLA nanoparticles).

The new adjuvant was injected into mice along with several antigens and fragments of viral proteins: two HIV antigens, diphtheria and influenza antigens. For comparison, FDA-approved adjuvants were included. It turned out that the new saponin-based nanoparticle elicits a stronger antibody response than other adjuvants.

When vaccines are injected into the arm, they travel through the lymphatic vessels to the lymph nodes, where they find and activate B cells. The research team found that the new adjuvant accelerates the flow of lymph to the nodes, helping the antigen get there before it breaks down. Stimulation of immune cells – mast cells – helps in part to this effect. Previously, scientists did not know that mast cells are involved in the body’s response to vaccines. In addition, once the vaccine reaches the lymph nodes, the adjuvant causes the macrophage cell layer to die off quickly (they act as a barrier), making it easier for the antigen to enter the nodes.

The earlier the B-lymphocyte sees the antigen, the higher the probability that it is not damaged, that is, the B-lymphocytes will attack a substance that is as similar to a virus as possible.

Darrell Irwin, Professor Underwood-Prescott
Another way that an adjuvant helps to boost the immune response is by activating inflammatory cytokines that trigger a stronger response. The TLR agonist that the researchers incorporated into the adjuvant is thought to enhance the cytokine response, but the exact mechanism is not yet known.

The new adjuvant may also be useful for other subunit vaccines composed of fragments of viral proteins or other molecules.

Researchers now want to include a new adjuvant in an HIV vaccine currently undergoing clinical trials to improve its effectiveness.