Adenovirus vector and mRNA vaccines: Mechanisms regulating their immunogenicity

Abstract

Replication‐incompetent adenovirus (Ad) vector and mRNA‐lipid nanoparticle (LNP) constructs represent two modular vaccine platforms that have attracted substantial interest over the past two decades. Due to the COVID‐19 pandemic and the rapid development of multiple successful vaccines based on these technologies, there is now clear real‐world evidence of the utility and efficacy of these platforms. Considerable optimization and refinement efforts underpin the successful application of these technologies. Despite this, our understanding of the specific pathways and processes engaged by these vaccines to stimulate the immune response remains incomplete. This review will synthesize our current knowledge of the specific mechanisms by which CD8 + T cell and antibody responses are induced by each of these vaccine platforms, and how this can be impacted by specific vaccine construction techniques. Key gaps in our knowledge are also highlighted, which can hopefully focus future studies.

Immune responses and clinical outcomes after COVID-19 vaccination in patients with liver disease and liver transplant recipients

“…mRNA and adenoviral vector platforms are thought to induce antibody production through varying biological pathways which may be differentially impacted by cirrhosis-associated immune dysfunction. 28 , 29 Further work is required to decipher the complex interplay between cirrhosis-associated immune dysfunction and immune responses to COVID-19 vaccination. Nonetheless, it is important to note that mRNA vaccines still induce higher antibody titres than ChAdOx1 at the post-V2 timepoint.…”

Subsequent COVID-19 Prophylaxis in COVID-19 Associated Glomerulopathies

“…Conversely, the immune response to vaccination is targeted to an attenuated virus or antigen, which for most COVID-19 vaccines is the viral spike (S) protein [ 54 ]. Further intricacies of the specific immune response varies according to the type of infection and/or vaccine [ 55 ]. In both instances the elimination of pathological microbes and proteins must be controlled so to avoid responses that produce excessive damage of self-tissues.…”

“…Autoantibodies to endogenous antigens via either molecular mimicry or antigenic injury, the release of proinflammatory mediators including cytokines, adjuvants in vaccines to augment the inflammatory response, and direct viral cytopathy with SARS-CoV-2 infection may all play a role in this process [ 57 , 58 , 59 ]. Whilst it is unclear, the mechanism of the vaccine type may have a role in such autoimmune disease pathogenesis, for instance stronger priming of CD8+ T cell responses by self-amplifying lipid encapsulated mRNA vaccination compared to adenoviral vector vaccines [ 55 ].…”

Lipid Nanoparticle (LNP) Delivery Carrier-Assisted Targeted Controlled Release mRNA Vaccines in Tumor Immunity

“…This would include further improving the design of LNPs and optimizing their distribution and stability in vivo in order to improve the delivery efficiency and antitumor effect of mRNA vaccines [ 211 ]. At the same time, according to different tumor types and individual patient differences, the development of personalized and customized LNP carriers and mRNA vaccine programs is also an important direction for future development [ 212 , 213 , 214 , 215 , 216 , 217 , 218 ]. LNP research in tumor immunotherapy will also focus more on safety and on the management of side effects.…”