Rresearchers from Monash University have developed a novel technique that significantly enhances the effectiveness of both traditional and mRNA-based vaccines in animal models. The core of this technology involves adding a low dose of vaccine-specific antibodies to the vaccine, which acts like a “booster shot” for the immune system.

The research findings were published online in the journal Immunity on September 20, 2024, with the paper titled “Conversion of vaccines from low to high immunogenicity by antibodies with epitope complementarity.”

Dr. Isaak Quast, the corresponding author and a researcher from the Department of Immunology at Monash University, explained: “A key challenge in vaccine design is ensuring sufficient activation and duration of B cell responses to achieve the quantity and quality of antibodies needed for protection. Adding vaccine-specific antibodies is like planting a red flag on the battlefield, making B cells very aware that they need to start acting.” This technique not only stimulates B cells that would otherwise not actively participate in the immune response but also helps identify new parts of the virus, thereby enhancing protective immunity.

Dr. Alexandra Dvorscek, the first author of the paper, pointed out that while most vaccines provide specificity and strength, it’s often difficult to achieve broad recognition and response. She said, “When you encounter viruses like influenza or SARS-CoV-2, which can change significantly over different years or even shorter periods and potentially cause significant harm, we need broad recognition and response.”

The immune system typically struggles to recognize conserved parts of viral proteins, which remain stable during viral evolution to evade immune detection. Dr. Dvorscek said, “Like adjuvants that enhance the immune system’s response to vaccination, adding antibodies can prolong the immune response and release more antibodies. The beauty of this technology is that, in collaboration with Dr. Deborah Burnett from the Garvan Institute of Medical Research, we’ve shown it works for both traditional vaccines and mRNA-based vaccines, such as those for SARS-CoV-2. This clearly has implications for existing vaccines and those under development, allowing us to enhance immune responses in a safe, highly targeted manner.”

In addition to enhancing B cell responses, antibodies can influence which viral structures can be targeted, ensuring the immune system responds to multiple parts of the pathogen. Dr. Dvorscek said, “Our research provides new insights into how this happens and how we can use it to guide antibody production where it’s needed for broad protective immune responses. We’ve found a way to potentially use the immune system’s own tools – antibodies – to influence how the body responds to vaccines. This could be particularly significant for those who respond poorly to vaccines, such as the elderly or immunocompromised individuals.”

Although this technology has only been tested in animal models so far, Dr. Quast stated that this research could also promote the development of vaccines targeting pathogen structures that the human immune system cannot adequately recognize. He said, “In diverse populations, some people always respond better than others, and this approach helps ensure that a larger proportion of the population produces a ‘good, sufficient’ immune response for protection.”

Dr. Quast added, “The method in this paper has the potential to significantly improve this typically poor response, and it works for both mRNA-based and traditional vaccines. One example we used was enhancing the SARS-CoV-2 mRNA vaccine developed by Professor Colin Pouton at the Monash Institute of Pharmaceutical Sciences.”

The proposed “cap proximity-driven translation” model provides valuable insights into mRNA translation mechanisms. This model could open up new avenues for mRNA design and potentially explain some previously observed phenomena in natural mRNA regulation.

Despite these concerns, the potential applications in vaccines and protein replacement therapies are enormously promising. The reported improvements in SARS-CoV-2 vaccine efficacy and hEPO expression in mice are particularly encouraging.

As we move forward, it will be crucial to balance the excitement of these new possibilities with rigorous safety assessments and ethical considerations. The mRNA-LNP field is evolving rapidly, and this work by Wang’s team represents a significant milestone in our journey towards more effective and versatile mRNA therapeutics.

Reference:

Alexandra R. Dvorscek al. Conversion of vaccines from low to high immunogenicity by antibodies with epitope complementarity. Immunity, 2024, doi:10.1016/j.immuni.2024.08.017.