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Utilizing the Antigen Capsid-Incorporation Strategy for the Development of Adenovirus Serotype 5-Vectored Vaccine Approaches
Published on: May 6, 2015
A modular mRNA vaccine platform encoding antigen-presenting capsid virus-like particles enhances the immunogenicity
Cyrielle Fougeroux1, Sven Hendrik Hagen1, Louise Goksøyr1
1AdaptVac Aps, Copenhagen, Denmark.
Abstract:
The COVID-19 pandemic has emphasized the potential of mRNA vaccines in fighting pandemics, owing to their rapid development, strong immunogenicity and adaptability. However, a drawback is their dose-limiting reactogenicity and inability to generate durable humoral immunity. Here we introduce a modular nucleotide vaccine platform combining the advantages of genetic and capsid virus-like-particle-based vaccines. This platform allows for the display of various antigens on different capsid virus-like particles, improving the magnitude, quality and longevity of the vaccine-induced immune responses. We applied this technology to enhance the immunogenicity of the Pfs25 antigen. Immunization with lipid-nanoparticle-formulated mRNA encoding Pfs25 capsid virus-like particles resulted in higher and potentially more durable anti-Pfs25 antibody responses, along with enhanced functional activity, compared with an mRNA vaccine encoding soluble Pfs25. By improving both humoral and cellular immune responses, this approach may reduce the dose and number of administrations required for effective protection. As a result, it can improve the feasibility of both DNA- and mRNA-based vaccines targeting pandemic and endemic infectious diseases.
Insights
This study introduces a novel vaccine platform combining mRNA and virus-like particles to improve immune responses against infectious diseases. This new approach enhances antibody durability and function, potentially reducing vaccine dosage and administration frequency.
Area of Science:
- Vaccinology
- Immunology
- Biotechnology
Background:
- Messenger RNA (mRNA) vaccines show promise for rapid development and adaptability during pandemics like COVID-19.
- However, current mRNA vaccines face challenges with dose-limiting reactogenicity and achieving long-lasting humoral immunity.
- Existing vaccine platforms have limitations in enhancing the magnitude, quality, and longevity of immune responses.
Purpose of the Study:
- To develop a modular nucleotide vaccine platform integrating genetic and capsid virus-like-particle (VLP) advantages.
- To enhance the immunogenicity of the Pfs25 antigen using this novel platform.
- To improve the durability and functionality of vaccine-induced immune responses.
Main Methods:
- Developed a modular vaccine platform enabling antigen display on different capsid VLPs.
- Formulated mRNA encoding Pfs25 VLPs using lipid nanoparticles.
- Administered the Pfs25 VLP mRNA vaccine to assess immune responses compared to soluble Pfs25 mRNA vaccine.
Main Results:
- The Pfs25 VLP mRNA vaccine induced higher and potentially more durable anti-Pfs25 antibody responses.
- Enhanced functional activity of antibodies was observed with the VLP-based approach.
- The platform demonstrated potential for improving both humoral and cellular immune responses.
Conclusions:
- The novel modular vaccine platform effectively enhances antigen immunogenicity and immune response longevity.
- This approach may reduce the required vaccine dose and number of administrations for effective protection.
- The technology holds promise for improving DNA and mRNA-based vaccines against pandemic and endemic infectious diseases.
