Immunization with HIV-1 envelope T20-encoding DNA vaccines elicits cross-clade neutralizing antibody responses

<p><b>Background:</b> Genetic immunization is expected to induce the expression of antigens in a native form. The encoded peptide epitopes are presented on endogenous MHC molecules, mimicking antigen presentation during a viral infection. We have explored the potential of enfuvirt...

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Main Authors: Stenler, S, Lundin, K, Hansen, L, Petkov, S, Mozafari, N, Isaguliants, M, Blomberg, P, Smith, C, Goldenberg, D, Chang, C, Ljungberg, K, Hinkula, J, Wahren, B
Format: Journal article
Published: Taylor and Francis 2017
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author Stenler, S
Lundin, K
Hansen, L
Petkov, S
Mozafari, N
Isaguliants, M
Blomberg, P
Smith, C
Goldenberg, D
Chang, C
Ljungberg, K
Hinkula, J
Wahren, B
author_facet Stenler, S
Lundin, K
Hansen, L
Petkov, S
Mozafari, N
Isaguliants, M
Blomberg, P
Smith, C
Goldenberg, D
Chang, C
Ljungberg, K
Hinkula, J
Wahren, B
author_sort Stenler, S
collection OXFORD
description <p><b>Background:</b> Genetic immunization is expected to induce the expression of antigens in a native form. The encoded peptide epitopes are presented on endogenous MHC molecules, mimicking antigen presentation during a viral infection. We have explored the potential of enfuvirtide (T20), a short HIV peptide with antiviral properties, to enhance immune response to HIV antigens. To generate an expression vector, the T20 sequence was cloned into a conventional plasmid, the novel minicircle construct, and a replicon plasmid. In addition, three conventional plasmids that express the envelope of HIV-1 subtypes A, B and C and contain T20 in their gp41 sequences were also tested. </p> <p><b>Results:</b> All combinations induced HIV-specific antibodies and cellular responses. The addition of T20 as a peptide and as an expression cassette in the three DNA vectors enhanced antibody responses. The highest anti-HIV-1 Env titers were obtained by the replicon T20 construct. This demonstrates that besides its known antiviral activity, T20 promotes immune responses. We also confirm that the combination of slightly divergent antigens improves immune responses. </p> <p><b>Conclusions:</b> The antiretroviral T20 HIV-1 sequence can be used as an immunogen to elicit binding and neutralizing antibodies against HIV-1. These, or similarly modified gp41 genes/peptides, can be used as priming or boosting components for induction of broadly neutralizing anti-HIV antibodies. Future comparative studies will reveal the optimal mode of T20 administration.</p>
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spelling oxford-uuid:4a0870ea-d366-4b6f-9c2d-e680f2aeb5332022-03-26T15:35:22ZImmunization with HIV-1 envelope T20-encoding DNA vaccines elicits cross-clade neutralizing antibody responsesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4a0870ea-d366-4b6f-9c2d-e680f2aeb533Symplectic Elements at OxfordTaylor and Francis2017Stenler, SLundin, KHansen, LPetkov, SMozafari, NIsaguliants, MBlomberg, PSmith, CGoldenberg, DChang, CLjungberg, KHinkula, JWahren, B <p><b>Background:</b> Genetic immunization is expected to induce the expression of antigens in a native form. The encoded peptide epitopes are presented on endogenous MHC molecules, mimicking antigen presentation during a viral infection. We have explored the potential of enfuvirtide (T20), a short HIV peptide with antiviral properties, to enhance immune response to HIV antigens. To generate an expression vector, the T20 sequence was cloned into a conventional plasmid, the novel minicircle construct, and a replicon plasmid. In addition, three conventional plasmids that express the envelope of HIV-1 subtypes A, B and C and contain T20 in their gp41 sequences were also tested. </p> <p><b>Results:</b> All combinations induced HIV-specific antibodies and cellular responses. The addition of T20 as a peptide and as an expression cassette in the three DNA vectors enhanced antibody responses. The highest anti-HIV-1 Env titers were obtained by the replicon T20 construct. This demonstrates that besides its known antiviral activity, T20 promotes immune responses. We also confirm that the combination of slightly divergent antigens improves immune responses. </p> <p><b>Conclusions:</b> The antiretroviral T20 HIV-1 sequence can be used as an immunogen to elicit binding and neutralizing antibodies against HIV-1. These, or similarly modified gp41 genes/peptides, can be used as priming or boosting components for induction of broadly neutralizing anti-HIV antibodies. Future comparative studies will reveal the optimal mode of T20 administration.</p>
spellingShingle Stenler, S
Lundin, K
Hansen, L
Petkov, S
Mozafari, N
Isaguliants, M
Blomberg, P
Smith, C
Goldenberg, D
Chang, C
Ljungberg, K
Hinkula, J
Wahren, B
Immunization with HIV-1 envelope T20-encoding DNA vaccines elicits cross-clade neutralizing antibody responses
title Immunization with HIV-1 envelope T20-encoding DNA vaccines elicits cross-clade neutralizing antibody responses
title_full Immunization with HIV-1 envelope T20-encoding DNA vaccines elicits cross-clade neutralizing antibody responses
title_fullStr Immunization with HIV-1 envelope T20-encoding DNA vaccines elicits cross-clade neutralizing antibody responses
title_full_unstemmed Immunization with HIV-1 envelope T20-encoding DNA vaccines elicits cross-clade neutralizing antibody responses
title_short Immunization with HIV-1 envelope T20-encoding DNA vaccines elicits cross-clade neutralizing antibody responses
title_sort immunization with hiv 1 envelope t20 encoding dna vaccines elicits cross clade neutralizing antibody responses
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