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Active versus Passive Immunity

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Updated: May 12, 2026

Sublingual Immunotherapy as an Alternative to Induce Protection Against Acute Respiratory Infections

Sublingual Immunotherapy as an Alternative to Induce Protection Against Acute Respiratory Infections

Published on: August 30, 2014

Circular mRNA against CleanCap linear mRNA vectors: comprehensive comparison, expression, active and passive

Vladimir M Vakhtinskii¹, Irina L Tutykhina¹, Alina S Dzharullaeva¹

¹Federal State Budget Institution "National Research Center for Epidemiology and Microbiology Named after the Honorary Academician N.F. Gamaleya", The Ministry of Health of the Russian Federation, Moscow, Russia.

Frontiers in Immunology

|May 11, 2026

Summary

Linear and circular mRNA vectors were compared for vaccine development. Modified linear mRNA vectors showed higher expression but similar immunogenicity to circular vectors in active immunization, yet offered better protection in passive immunization models.

Keywords:

ARCA CVB3 IRES CleanCap HRVB6 IRES SARS-CoV2 vaccine circular mRNA circular mRNA-vaccine universal vector platform

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Simultaneous Quantification of Anti-vector and Anti-transgene-Specific CD8+ T Cells Via MHC I Tetramer Staining After Vaccination with a Viral Vector

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Published on: November 28, 2018

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Simultaneous Quantification of Anti-vector and Anti-transgene-Specific CD8+ T Cells Via MHC I Tetramer Staining After Vaccination with a Viral Vector

Simultaneous Quantification of Anti-vector and Anti-transgene-Specific CD8⁺ T Cells Via MHC I Tetramer Staining After Vaccination with a Viral Vector

Published on: November 28, 2018

Area of Science:

Molecular Biology
Vaccinology
Biotechnology

Background:

Messenger RNA (mRNA) technology has transformed vaccine development due to its universal, rapid, and scalable production.
Two primary mRNA vector types, linear (cap-dependent) and circular (cap-independent), offer distinct advantages.
A comprehensive comparative analysis of the most effective vectors of each type was lacking.

Purpose of the Study:

To compare the expression efficiency, protective activity, and therapeutic activity of circular and linear mRNA vectors.
To evaluate different configurations of linear and circular mRNA vectors for optimal performance.

Main Methods:

Compared linear and circular mRNA vectors using luciferase reporter assays and target protein expression.
Assessed protective activity via active immunization (immunogenicity and SARS-CoV-2 challenge) and passive immunization (antibody production and toxin challenge).
Tested linear vectors with N1-methylpseudouridine or uridine and ARCA or CleanCap, and circular vectors with different IRES elements.

Main Results:

Modified linear mRNA vectors demonstrated significantly higher expression levels both in vitro and in vivo compared to circular vectors.
Active immunization studies showed comparable immunogenicity and protective activity between linear and circular vectors.
Linear vectors provided significantly better protection in passive immunization models, correlating with higher in vivo protein expression.

Conclusions:

While modified linear mRNA vectors exhibit superior expression, they did not outperform circular vectors in active immunization immunogenicity or protection.
Linear mRNA vectors appear to be a better choice for passive immunization strategies that necessitate high target protein expression levels.