A potent novel vaccine adjuvant could help make vaccines against HIV and other infectious diseases.

An adjuvant — a substance that stimulates the immune system to produce a higher reaction — is a popular strategy for making vaccines more effective.

Researchers at MIT, the La Jolla Institute for Immunology, and other institutions have developed a novel nanoparticle adjuvant that may be more effective than those already in use. It greatly enhanced antibody production following vaccination against HIV, diphtheria, and influenza in mice studies.

“We started looking at this particular formulation and found that it was incredibly potent, better than almost anything else we had tried,” said Darrell Irvine, an associate director of MIT’s Koch Institute for Integrative Cancer Research; and a member of the Ragon Institute of MGH, MIT, and Harvard.

The researchers now intend to include the adjuvant into an HIV vaccine already being studied in clinical trials in order to improve its performance.

Despite the fact that the concept of employing adjuvants to increase vaccine effectiveness has been known for decades, there are just a few FDA-approved vaccine adjuvants. Aluminum hydroxide, an aluminum salt that causes inflammation, and an oil and water emulsion used in flu vaccines are two examples. The FDA approved an adjuvant based on saponin, a chemical obtained from the bark of the Chilean soapbark tree, a few years ago.

Saponin in liposomes is presently employed as an adjuvant in the shingles vaccine, and saponins are also used in a cage-like nanoparticle known as an immunostimulatory complex (ISCOM) in a Covid-19 vaccine that is currently in clinical development.

Saponins have been demonstrated to increase inflammatory immune responses and stimulate antibody formation, although how they do so is unknown. The MIT and La Jolla team wanted to figure out how the adjuvant works and see if they could make it more potent in the latest trial.

They created a novel type of adjuvant that is comparable to the ISCOM adjuvant but additionally contains a toll-like receptor agonist called MPLA. These chemicals cause inflammation when they attach to toll-like receptors on immune cells. The novel adjuvant is known as SMNP (saponin/MPLA nanoparticles) by the researchers.

“We expected that this could be interesting because saponin and toll-like receptor agonists are both adjuvants that have been studied separately and shown to be very effective,” said Irvine.

The researchers put the adjuvant to the test by injecting it into mice along with a variety of antigens, or viral protein fragments. Two HIV antigens, as well as diphtheria and influenza antigens, were among them. They tested the adjuvant against several other approved adjuvants and discovered that the new saponin-based nanoparticle generated a greater antibody response than any of the others.

They used an HIV envelope protein nanoparticle, which contains numerous copies of the gp120 antigen seen on the HIV viral surface, as one of the HIV antigens. This antigen recently finished preliminary testing in phase 1 clinical trials. Irvine and Crotty are members of the Scripps Research Institute’s Consortium for HIV/AIDS Vaccine Development, which oversaw the experiment. The researchers now seek to create a method to mass-produce the novel adjuvant so that it may be tested alongside an HIV envelope trimer in another clinical trial starting next year. Clinical experiments combining envelope trimers and the standard vaccination adjuvant aluminum hydroxide are also being conducted.

“Aluminum hydroxide is safe but not particularly potent, so we hope that (the new adjuvant) would be an interesting alternative to elicit neutralizing antibody responses in people,” added Irvine.

Vaccines are injected into the arm and pass through lymph veins to the lymph nodes, where they interact with and activate B cells. The researchers discovered that the novel adjuvant accelerates the flow of lymph to the nodes, allowing the antigen to reach the nodes before it begins to degrade. It accomplishes this in part by rousing immune cells known as mast cells, which were previously unknown to be involved in vaccine responses.

“Getting to the lymph nodes quickly is useful because once you inject the antigen, it starts slowly breaking down. The sooner a B cell can see that antigen, the more likely it’s fully intact, so that B cells are targeting the structure as it will be present on the native virus,” Irvine explained.

Furthermore, as the vaccine reaches the lymph nodes, the adjuvant induces a layer of cells called macrophages, which operate as a barrier, to die off quickly, allowing the antigen to enter the nodes more easily.

Another method the adjuvant aids in immune response enhancement is by stimulating inflammatory cytokines, which promote a greater response. The TLR agonist added in the adjuvant by the researchers is thought to boost that cytokine response, but the specific mechanism is unknown.

This type of adjuvant could also be effective for any other type of subunit vaccine that consists of viral protein fragments or other compounds. In addition to HIV vaccines, the researchers are collaborating with J. Christopher Love’s group at the Koch Institute on a potential Covid-19 vaccine. The novel adjuvant also appears to aid in the stimulation of T cell activity, which could make it beneficial as a component of cancer vaccines that try to encourage the body’s own T cells to attack tumors.

Source: MIT

Image Credit: Getty

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