Dr. Pablo Penaloza McMaster, associate professor of microbiology and immunology, was senior author of the study published in the Journal of Clinical Investigation.
In a recent study published in the Journal of Clinical Investigation, researchers led by Dr. Pablo Penaloza-McMaster, associate professor of microbiology and immunology, found that administering antibody treatment four days after mRNA vaccination. They found that the immune response in mice and the effectiveness of the vaccine were increased. .
The findings suggest potential strategies to advance the development of mRNA vaccines to treat infectious diseases such as HIV, coronaviruses and cancer.
During the COVID-19 pandemic, mRNA vaccines are highly effective in preventing severe infection and death from SARS-CoV-2, the virus that causes COVID-19. It was proven that. These vaccines utilize lab-engineered mRNA to produce viral proteins that activate the body’s adaptive immune response.
Current mRNA vaccines are effective in reducing severe SARS-CoV-2 infection, but have limited immunity durability and often require multiple booster doses to increase efficacy . Penaloza-McMaster said it was also not possible to completely prevent breakthrough infections, underscoring the need for improved vaccine strategies.
In this study, Dr. Penaloza-McMaster and his team investigated whether they could increase the effectiveness of mRNA vaccines by using costimulatory antibodies to enhance the costimulatory response known as 4-1BB. I investigated.
“Activation of T cells requires at least two important signals known as antigen and co-stimulation,” Penaloza-McMaster said. “It’s like starting a car. The antigen is the key, and it perfectly matches the T cells and turns on the car. But you also have to press the gas pedal, and that’s the co-stimulus. .”
However, previous attempts to boost T-cell responses by providing costimulatory antibodies during vaccination have failed, so administering both signals at the same time may have the opposite effect, Penaloza-McMaster says. he said.
This led the researchers to consider whether delaying costimulatory treatment until several days after the first mRNA vaccination could better support T cell activation and improve vaccine efficacy. .
“It looks like you have to turn on the key and let the car warm up before you hit the gas pedal,” Penaloza-McMaster said.
First, the researchers immunized mice with various mRNA vaccines and administered low doses of 4-1BB costimulatory antibodies at the time of vaccination or four days later. These antibodies, which promote T cell activation, have been previously tested in the treatment of autoimmune diseases and cancer immunotherapy and have been shown to be safe at low doses.
The researchers found that administering low doses of 4-1BB costimulatory antibodies at the time of vaccination did not significantly enhance the mice’s immune response. However, delaying this treatment by 4 days significantly improved CD8 T cell responses and increased the durability of immune responses across multiple mRNA vaccines, including SARS-CoV-2, HIV-1, and cancer.
“We have observed improved efficacy of mRNA vaccines,” Penaloza-McMaster said. “We exposed mice to a variety of pathogens several weeks after vaccination, and those treated with delayed co-stimulation therapy on day four cleared the infection more effectively than mice that received no treatment. This fourth day of treatment also improved the effectiveness of the cancer vaccine.”
According to Penaloza-MacMaster, these findings highlight the importance of the timing of co-stimulation to improve the efficacy of mRNA vaccines and reduce the likelihood of breakthrough infections.
“These data also justify a reappraisal of the classic textbook model in immunology, in which T cells must simultaneously receive antigen and co-stimulation, although these two signals are essential for T cell activation. , our data suggest that the time interval between these signals may enhance T-cell responses following vaccination,” Penaloza-McMaster said.
Sara Sanchez, a student in the Driskill Graduate Program (DGP) in Life Sciences, is the study’s lead author.
Co-authors include Dr. Tanushree Dangi, a research associate at Northwestern University. Dr. Min Han Lew, Postdoctoral Researcher in the Penaloza-McMaster Lab. Bakare Awakoaiye, Medical Scientist Training Program (MSTP) student; Nahid Irani, Science Immersion Program (SIP) student. Dr. Slim Forlaty is an assistant professor of medicine in the Department of Allergy and Immunology.
Penaloza-MacMaster is also a member of the Robert H. Lurie Comprehensive Cancer Center at Northwestern University.
This research was supported by the National Institute on Drug Abuse (grant DP2DA051912), the Third Coast Center for AIDS Research (CFAR), and the National Institute of Allergy and Infectious Diseases (grant 1R56AI187084).
