Scientists from La Jolla Institute for Immunology (LJI) and Massachusetts Institute of Technology (MIT) have discovered a possible way to improve the effectiveness of COVID-19 vaccines – and any vaccine.
Their research, published in Science Immunology indicates that a “combination adjuvant” called a saponin/TLR antagonist may enhance the effectiveness of the vaccine.
This is very exciting. We are really excited about the potential of this adjuvant.”
Shane Crotty, Ph.D., LJI Professor, Member, LJI Center for Infectious Disease and Vaccine Research
Vaccines are effective because they show the human immune system just a small part of a pathogen. The immune system is able to recognize the “antigen” and begins to produce the immune cells and antibodies necessary to fight the actual virus.
Antigens seldom function on their own. Scientists utilize adjuvants in most vaccine designs. Adjuvants act as red flags that trigger the immune system to react more strongly to the antigen and create the well-honed T cells and B cells that protect the body for a long time.
Five adjuvants are the only ones approved by the FDA to be used in the United States. Crotty is a world-renowned expert in vaccine research, believes scientists need new adjuvant options as they design more innovative vaccines against viruses like SARS-CoV-2 and HIV.
Crotty states that licensed vaccines depend on adjuvants. There are very few adjuvants for human use.
“New adjuvants that help drive specific aspects of antibody or T cell-mediated immunity could be a key component in developing effective vaccines against difficult pathogens such as HIV, malaria, and TB,” adds study co-leader MIT Professor Darrell Irvine, Ph.D., who also serves as an investigator for the Howard Hughes Medical Institute.
Meet the SMNP adjuvant
The scientists were interested in testing a combination saponin/TLR agonist adjuvant because the two molecules have demonstrated promise when tested separately. The safety of the saponin adjuvants has been proven and they are approved to be used in the Shingrix vaccine against shingles. TLR agonists have been proven to stimulate the innate immune system, which is the system that detects antigens first.
Irvine’s lab was responsible for the design and synthesizing the adjuvant saponin/TLR antagonist adjuvant. There are a variety of TLR agonists, so the researchers decided to test a TLR4 agonist known as MPLA. The molecule creates nanoparticles of MPLA and saponin by naturally joining with saponin molecules.
At LJI, Scientific Associate Yu Kato, Ph.D., started by spearheading experiments to understand exactly what makes saponin adjuvants efficient.
Experiments in mice showed that an adjuvant containing saponin triggers a strong response from the body’s germinal centers, lymph nodes, which are structures that pump out B cells. A saponin adjuvant was also found to have better T cell and class-switched antibody response (which allows antibodies to switch targets as they grow) than a variety of other adjuvants.
Kato found that saponin makes an impact because it promotes a process called lymphatic drainage. This is where lymphatic fluid flows into lymph nodes and alerts immune cells throughout the body to the presence of an invading pathogen.
Although the saponin adjuvant by itself led to a good response in mice, the TLR agonist was the secret weapon. The scientists studied how the immune system responded when both adjuvants were combined with an HIV-related protein HIV (a vaccine candidate that was developed by the Center for HIV/AIDS Vaccine Immunology & Immunogen Discovery (CHAVI-ID) at Scripps Research).
What is unique about SMNP
Researchers discovered that the combination of SMNP and SMNP activates many parts of the immune system. While saponin and the TLR agonist perform their functions, combining them also prompts the immune system to make more kinds of T Follicular Helper Cells, which strengthen the immune system, and more interleukin-21, an antiviral molecule.
Kato says, “It was more that an additive effect.” “The combination of the two led to more B cells, and B cells need to produce antibodies to be able to utilize those T Follicular Support Cells.”
The researchers concluded that SMNP was safe and efficient. Although more clinical research is needed to be done, Crotty says several applications for SMNP are immediately in mind. Crotty believes that SMNP could be a valuable addition to Novavax COVID-19 vaccine. The vaccine currently employs a traditional protein adjuvant.
Crotty says, “This could have a significant impact on human health.”
Kato explains that it is essential to develop new adjuvants to stop the spread of HIV. Scientists have been trying to develop an efficient HIV vaccine for more than 30 years, but it has been tough to get the immune system to create an effective response to a vaccine.
“If we continue to do the same thing, the vaccines are not going to be effective,” Kato says. “We need to do things smarter. It is therefore crucial that we understand how adjuvants work.
Silva, M., and others. (2021). A particulate/TLR agonist vaccine adjuvant alters Lymph flow and regulates adaptive immune. Science Immunology. doi.org/10.1126/sciimmunol.abf1152.
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