New vaccine ingredient may create a stronger defense against many illnesses — including COVID-19

LA JOLLA, Calif. — A new vaccine ingredient may soon boost the effectiveness of the COVID-19 vaccine and even create a new defense against illnesses like HIV. Scientists from the La Jolla Institute for Immunology and MIT created a “combination” adjuvant called a saponin/TLR agonist which they believe will increase the power of all vaccines.

“This is super exciting,” says LJI Professor Shane Crotty, Ph.D., a member of the LJI Center for Infectious Disease and Vaccine Research, in a media release. “We’re really hoping this adjuvant can help out.”

Current vaccines only use a few adjuvants

Vaccines work by teaching a person’s immune system to recognize a virus and response to it by producing antibodies. To do this, the vaccine shows a patient’s immune system a small piece of the pathogen, an antigen, so it knows what to attack.

The antigens aren’t the only thing vaccines use however, as scientists often add adjuvants to the mix. These particles act like a red flag that the human immune system reacts to more aggressively than just an antigen by itself. The immune response develops well-trained T cells to fight infections and memory B cells which continue to remember the virus for years.

Despite their effectiveness, researchers explain that the U.S. Food and Drug Administration (FDA) have only approved five kinds of adjuvants for use in vaccines. Dr. Crotty says the world needs new adjuvants to create more effective and innovative vaccines to battle serious viruses like COVID and HIV.

“Licensed vaccines depend on adjuvants, and there are very few adjuvants available for use in humans,” Crotty reports.

“New adjuvants that help drive particular aspects of antibody or T cell-mediated immunity may be an important part of successfully developing vaccines against challenging pathogens such as HIV, TB, and malaria,” adds study co-leader and MIT professor Darrell Irvine, Ph.D.

How does the new adjuvant work?

The team wanted to test a combination of saponin and TLR agonist adjuvants after seeing how well both worked on their own. Study authors note saponin adjuvants are a safe and effective component of the Shingrix vaccine for shingles. Meanwhile, TLR agonists show the ability to stimulate the body’s innate immune response — which first recognizes antigens.

For this study, researchers chose a TLR4 agonist called MPLA out of the many TLR agonist options available. This one naturally joins together with saponin molecules, forming saponin/MPLA nanoparticles (SMNP).

Tests using mice revealed that saponin adjuvants alone trigger a strong reaction from a patient’s germinal centers. These are areas of the body’s lymph nodes which produce the memory B cells that protect patients from future infections.

Although saponin adjuvants on their own create a strong antibody response in mice, the study finds the TLR agonist are the “secret weapon” of this new vaccine candidate. The combination activates a wide range of areas within the immune system. Although saponins and TLR agonists have their own jobs, they team up to push the immune system into making more immune-strengthening T follicular helper cells and antiviral interleukin-21 molecules.

“It was more than just an additive effect,” says LJI Scientific Associate Yu Kato, Ph.D. “The combination led to more way more B cells too, and for B cells to produce antibodies, they need help from those T follicular helper cells.”

HIV vaccine on the way?

The study finds this new vaccine formula appears to be safe and effective, according to the mice experiments. Although the SMNP adjuvant still has a way to go before it becomes an option for future vaccines, the team believes it may be a good addition to the current COVID-19 shots which use a traditional protein adjuvant.

“This has, potentially, a big impact for human health,” Crotty says.

The new design may also provide a template for stopping the spread of HIV. Over the last 30 years, scientists have continued to struggle to create a serious immune response within patients.

“If we keep doing the same thing, these vaccines are not going to work,” Kato concludes. “We need to do things smarter. That’s why it is critical for us to understand how adjuvants really work.”

The study is published in the journal Science Immunology.