March 2, 2024

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COVID Vaccines: Contrasting mRNA and Protein for Germinal Center Responses

COVID Vaccines: Contrasting mRNA and Protein for Germinal Center Responses



COVID Vaccines: Contrasting mRNA and Protein for Germinal Center Responses.

Comparison of mRNA Vaccine and Recombinant Protein Vaccine in Inducing Antigen-Specific Germinal Center Responses.

The deployment of effective vaccines against SARS-CoV-2 is crucial for eradicating the COVID-19 pandemic. Many authorized vaccines provide protection by inducing long-lived plasma cells (LLPCs) and memory B cells (MBCs), typically generated in germinal center (GC) reactions.

Professor Michela Locci’s team at the University of Pennsylvania compared two vaccine platforms – mRNA vaccines and recombinant protein vaccines formulated with MF59-like adjuvants – to assess their quantitative and qualitative abilities in eliciting SARS-CoV-2-specific primary GC responses over time. In December 2020, their study titled “SARS-CoV-2 mRNA Vaccines Foster Potent Antigen-Specific Germinal Center Responses Associated with Neutralizing Antibody Generation” was published in Immunity.

COVID Vaccines: Contrasting mRNA and Protein for Germinal Center Responses

Using experimental techniques such as flow cytometry, immunofluorescence, qPCR, the researchers demonstrated that a single immunization with the SARS-CoV-2 mRNA vaccine could trigger effective SARS-CoV-2-specific GC B cell and GC Tfh cell responses within 7 days. LLPCs and MBCs were detected 60 days later, showing a significant advantage over the recombinant protein vaccine (including MF59-like adjuvant). Importantly, the GC response was closely correlated with the production of neutralizing antibodies, as evidenced in the article. mRNA vaccines more effectively induced key regulatory factors for Tfh cell development and influenced the functional characteristics of Tfh cells. Overall, the study identified the SARS-CoV-2 mRNA vaccine as a robust candidate for promoting GC-derived immune responses.

Seven days after a single immunization, the recombinant protein vaccine (rRBD-AddaVax) failed to induce detectable GC B cells (Fas+ GL7+ B cells) compared to non-immunized mice. In contrast, both SARS-CoV-2 mRNA vaccines (encoding S protein or RBD) induced robust groups of GC B cells. At this early time point, SARS-CoV-2 mRNA vaccines, especially the full-length S protein mRNA vaccine, also had an advantage in inducing short-lived plasma cells (PCs).

In summary, their research provided a detailed quantitative and qualitative overview of the GC responses induced by two types of SARS-CoV-2 vaccines and revealed the close connection between the generation of neutralizing antibodies and SARS-CoV-2-specific GC responses. With several candidate vaccines considered for combating the COVID-19 pandemic, this study establishes a baseline for evaluating the immune responses induced by SARS-CoV-2 candidate vaccines in future preclinical and clinical research.

COVID Vaccines: Contrasting mRNA and Protein for Germinal Center Responses

References:

Lederer K, Castaño D, Gómez Atria D, et al. SARS-CoV-2 mRNA Vaccines Foster Potent Antigen-Specific Germinal Center Responses Associated with Neutralizing Antibody Generation. Immunity. 2020 Dec 15;53(6):1281-1295.e5. doi: 10.1016/j.immuni.2020.11.009.

(source:internet, reference only)


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