Prime-boost vaccination with a combination of proteosome-degradable and wild-type forms of two influenza proteins leads to augmented CTL response.

Vaccine
P O IlyinskiiA M Shneider

Abstract

Targeting viral antigens for proteosomal degradation has previously been proposed as a means for immunogenicity augmentation. However, utilization of modified unstable antigens may be insufficient for potent T-cell cross-presentation by APCs, a mechanism that requires high levels of the antigenic protein. Therefore, we hypothesized that a recombinant vaccine utilizing a combination of proteosome-sensitive and proteosome-resistant versions of an antigen in a prime-boost regimen may provide the most efficient CTL response. To address this hypothesis, we utilized conserved proteosome-resistant influenza A virus proteins M1 and NS1. Unstable versions of these polypeptides were constructed by destroying their 3D structure via truncations or short insertions into predicted alpha-helical structures. These modified polypeptides were stabilized in the presence of the proteosome inhibitor MG132, strongly suggesting that they are degraded via a ubiquitin-proteosome pathway. Importantly, with both M1 and NS1antigens, homologous DNA vaccination with a mixture of unstable and proteosome-resistant wt forms of these proteins resulted in significantly higher CTL activity than vaccination with either wt or degradable forms. The most dramatic eff...Continue Reading

References

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Citations

Jul 15, 2009·Omics : a Journal of Integrative Biology·Petr O IlyinskiiAlexander M Shneider
Dec 10, 2008·International Reviews of Immunology·Petr O IlyinskiiAlexander M Shneider
Apr 16, 2008·Protein Science : a Publication of the Protein Society·Petr O IlyinskiiAlexander M Shneider
Oct 4, 2014·International Reviews of Immunology·Vladimir L Gabai, Victor I Shifrin
Feb 26, 2010·FEMS Microbiology Reviews·Stuart D PerkinsHelen S Atkins
Oct 15, 2013·Oncotarget·Franco VenanziAlexander Shneider
Feb 22, 2017·The Journal of General Virology·Yulia V KuzmenkoVadim L Karpov
Jul 18, 2019·Frontiers in Immunology·Maria AuladellKatherine Kedzierska

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