Vector delivery-dependant effect of human tissue plasminogen activator signal peptide on vaccine induction of T cells

Attachment of the human tissue plasminogen activator signal peptide (tPA-SP) to a variety of proteins has enhanced the induction of both antibody and cellular immune responses in animal models. Here, as part of a continuing effort to improve HIV-1 vaccine immunogenicity, we sought to determine wheth...

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Main Authors: Hanke, T, Ondondo, B, Abdul-Jawad, S, Roshorm, Y, Bridgeman, A
Format: Journal article
Published: Sci Forschen 2016
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author Hanke, T
Ondondo, B
Abdul-Jawad, S
Roshorm, Y
Bridgeman, A
author_facet Hanke, T
Ondondo, B
Abdul-Jawad, S
Roshorm, Y
Bridgeman, A
author_sort Hanke, T
collection OXFORD
description Attachment of the human tissue plasminogen activator signal peptide (tPA-SP) to a variety of proteins has enhanced the induction of both antibody and cellular immune responses in animal models. Here, as part of a continuing effort to improve HIV-1 vaccine immunogenicity, we sought to determine whether or not addition of optimized tPA-SP improves the magnitude and functionality of T cells elicited by vaccines expressing protein HIVconsv derived from highly conserved regions of the HIV-1 proteome. The HIVconsv vaccines were vectored by plasmid DNA, non-replicating simian (chimpanzee) adenovirus ChAdV63 and non-replicating poxvirus MVA. We found that addition of the tPA-SP increased levels of intracellular HIVconsv protein for all the tested vaccines. When administered intramuscularly to the BALB/c mice, a 2- to 3.5-fold increase in frequencies of vaccine-elicited T-cells were observed for the DNA modality, however, there was no consistent significant improvement when using a much more potent heterologous regimen of ChAdV63 prime-MVA boost. Our results concur with previous DNA studies and emphasize that immunopotentiation by the tPA-SP is likely immunogen, vaccine modality, type of immune responses and species specific. Thus, the tPA-SP effect on induction of desired immune responses should be assessed for each vaccine strategy separately.
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spelling oxford-uuid:86b3a2ab-2c7d-403e-98ce-5717d5c979262022-03-26T22:05:45ZVector delivery-dependant effect of human tissue plasminogen activator signal peptide on vaccine induction of T cellsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:86b3a2ab-2c7d-403e-98ce-5717d5c97926Symplectic Elements at OxfordSci Forschen2016Hanke, TOndondo, BAbdul-Jawad, SRoshorm, YBridgeman, AAttachment of the human tissue plasminogen activator signal peptide (tPA-SP) to a variety of proteins has enhanced the induction of both antibody and cellular immune responses in animal models. Here, as part of a continuing effort to improve HIV-1 vaccine immunogenicity, we sought to determine whether or not addition of optimized tPA-SP improves the magnitude and functionality of T cells elicited by vaccines expressing protein HIVconsv derived from highly conserved regions of the HIV-1 proteome. The HIVconsv vaccines were vectored by plasmid DNA, non-replicating simian (chimpanzee) adenovirus ChAdV63 and non-replicating poxvirus MVA. We found that addition of the tPA-SP increased levels of intracellular HIVconsv protein for all the tested vaccines. When administered intramuscularly to the BALB/c mice, a 2- to 3.5-fold increase in frequencies of vaccine-elicited T-cells were observed for the DNA modality, however, there was no consistent significant improvement when using a much more potent heterologous regimen of ChAdV63 prime-MVA boost. Our results concur with previous DNA studies and emphasize that immunopotentiation by the tPA-SP is likely immunogen, vaccine modality, type of immune responses and species specific. Thus, the tPA-SP effect on induction of desired immune responses should be assessed for each vaccine strategy separately.
spellingShingle Hanke, T
Ondondo, B
Abdul-Jawad, S
Roshorm, Y
Bridgeman, A
Vector delivery-dependant effect of human tissue plasminogen activator signal peptide on vaccine induction of T cells
title Vector delivery-dependant effect of human tissue plasminogen activator signal peptide on vaccine induction of T cells
title_full Vector delivery-dependant effect of human tissue plasminogen activator signal peptide on vaccine induction of T cells
title_fullStr Vector delivery-dependant effect of human tissue plasminogen activator signal peptide on vaccine induction of T cells
title_full_unstemmed Vector delivery-dependant effect of human tissue plasminogen activator signal peptide on vaccine induction of T cells
title_short Vector delivery-dependant effect of human tissue plasminogen activator signal peptide on vaccine induction of T cells
title_sort vector delivery dependant effect of human tissue plasminogen activator signal peptide on vaccine induction of t cells
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