Vaccine News - AAV vectors show promise in directly delivering antibodies that target SARS-CoV-2
Nikhil Prasad Fact checked by:Thailand Medical News Team Jul 17, 2024 4 months, 5 days, 14 hours, 18 minutes ago
Vaccine News: In a significant development for protecting vulnerable populations from COVID-19, German researchers from the University Hospital Erlangen, Leiden University Medical Center, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Fraunhofer Institute for Cell Therapy and Immunology (IZI), Sirion Biotech GmbH, and the University of Heidelberg have explored a novel approach to passive immunization using Adeno-associated virus (AAV) vectors. This
Vaccine News report delves into their findings and the potential implications for long-term protection against SARS-CoV-2.
Vaccine News - AAV vectors show promise in directly delivering antibodies that target SARS-CoV-2
A New Hope for Immunocompromised Individuals
Despite the availability of COVID-19 vaccines, individuals with weakened immune systems, such as organ transplant recipients and cancer patients undergoing chemotherapy, remain at high risk for severe COVID-19. Furthermore, there has been a lot of questions about the efficacy of these existing COVID-19 vaccines and also the adverse effects from the usage of the vaccines are now raising questions as to whether these vaccines should have been approved in the first place and even forced upon many by health authorities and governments.
For groups with a weakened immune system, traditional vaccines may not elicit a strong enough immune response. The study conducted by Dr Jannik T. Wagner and colleagues aims to address this challenge through passive immunization, where pre-made antibodies are delivered directly into the body.
The Role of AAV Vectors
AAV vectors are small, non-enveloped viruses that can deliver therapeutic genes to target cells. They are known for their low immunogenicity and long-lasting expression, making them ideal for gene therapy. In this study, the researchers constructed AAV vectors encoding the TRES6 antibody, a potent neutralizer of SARS-CoV-2, and packaged them into two types of capsids: hepatotropic (AAV8) and myotropic (AAVMYO).
Key Findings from the Study
Long-Lasting Antibody Expression: Mice injected with the myotropic AAVMYO vector exhibited the highest serum concentrations of the TRES6 antibody, with levels peaking at 511 µg/ml after 24 weeks. These levels remained above 100 µg/ml for at least one year, providing sustained protection against SARS-CoV-2.
Absence of Anti-Drug Antibodies: Importantly, no anti-drug antibodies or TRES6-specific T cells were detected in the mice, indicating that the AAV-delivered antibodies did not provoke an immune response against themselves.
Tissue Tropism and mRNA Expression: The study revealed that after injection of the AAV8 particles, vector mRNA was primarily detected in the liver, while AAVMYO particles led to high vector mRNA levels in the heart and skeletal muscle. This tissue-specific expression is crucial for understanding the distribution and efficacy of the
delivered antibodies.
Fc-Glycosylation Patterns and Fc-γ Receptor Binding: Analysis of the glycosylation patterns of the TRES6 antibodies showed significant differences between the capsids, affecting their binding activities to murine Fc-γ receptors. This could influence the antibodies' effectiveness and longevity.
Protecting Against COVID-19
The AAV vector-based immune prophylaxis demonstrated full protection against lethal SARS-CoV-2 infection in K18-hACE2 mice, a model that allows for viral replication and disease development. Mice that received AAV vector-delivered TRES6 antibodies showed no weight loss and only mild clinical symptoms after being challenged with the virus.
Implications for Human Health
The findings from this study are promising for the development of long-acting passive immunization strategies to protect immunosuppressed individuals from COVID-19 and other infectious diseases. The high and sustained expression levels of the TRES6 antibody, combined with the absence of adverse immune responses, warrant further exploration of AAV vector-based delivery systems.
Future Directions
The researchers suggest that further studies are needed to optimize the delivery system and explore the potential of AAV vectors for other biologicals. They highlight the importance of understanding the glycosylation patterns and their impact on the antibodies' function. Additionally, the use of different AAV capsids and promoter systems could enhance tissue-specific expression and reduce potential side effects.
Conclusion
This groundbreaking research opens new avenues for protecting vulnerable populations from COVID-19. By leveraging the unique properties of AAV vectors, the study provides a foundation for developing long-term immunization strategies that could offer robust and sustained protection.
The study findings were published in the peer-reviewed journal: Communications Biology.
https://www.nature.com/articles/s42003-024-06529-3
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