A recent study published in The Journal of Clinical Investigation reveals that delaying antibody treatment following mRNA vaccination can significantly enhance immune responses and vaccine efficacy. The research, led by Pablo Penaloza-MacMaster, PhD, associate professor of Microbiology-Immunology at Northwestern University, suggests a novel approach to improve mRNA vaccine development for infectious diseases and cancer.
Enhancing Immune Response Through Delayed Costimulation
The study addresses limitations in current mRNA vaccines, such as waning immune durability and breakthrough infections. Penaloza-MacMaster and his team explored whether reinforcing a costimulatory response, specifically 4-1BB, with costimulatory antibodies could enhance vaccine effectiveness. According to Penaloza-MacMaster, T-cell activation requires both antigen and costimulation signals, but administering them simultaneously has proven counterproductive in previous studies.
Timing is Key
To investigate the impact of timing, the researchers immunized mice with mRNA vaccines and administered a low dose of 4-1BB costimulatory antibodies either at the time of vaccination or four days later. The 4-1BB antibodies, known to promote T-cell activation, have been tested in autoimmune disease and cancer immunotherapy treatments and have demonstrated safety at low doses.
The study found that administering the 4-1BB antibody at the time of vaccination did not significantly improve the immune response in mice. However, delaying the treatment by four days led to a significant enhancement in CD8 T-cell responses and increased the durability of immune responses across multiple mRNA vaccines, including those targeting SARS-CoV-2, HIV-1, and cancer.
Improved Vaccine Efficacy
"We observed an improvement in the efficacy of mRNA vaccines," said Penaloza-MacMaster. The study demonstrated that mice treated with the delayed costimulatory therapy cleared infections more effectively than those that did not receive the treatment. This improvement was also observed in cancer vaccines.
Implications for Future Vaccine Development
These findings highlight the importance of the timing of co-stimulation in improving mRNA vaccine efficacy and reducing the likelihood of breakthrough infections. The results challenge the traditional immunology model that T-cells must receive antigen and costimulation simultaneously for activation. The study suggests that a time interval between these signals can enhance T-cell responses after vaccination.
The research was supported by grants from the National Institute on Drug Abuse, the Third Coast Centers for AIDS Research, and the National Institute of Allergy and Infectious Diseases.
