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Codon optimization ...
Codon optimization and improved delivery/immunization regimen enhance the immune response against wild-type and drug-resistant HIV-1 reverse transcriptase, preserving its Th2-polarity
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- Latanova, A. A. (author)
- Russian Acad Sci, Russia; Karolinska Inst, Sweden; Gamaleja Res Ctr Epidemiol and Microbiol, Russia
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- Petkov, S. (author)
- Karolinska Institutet,Karolinska Inst, Sweden
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- Kilpelainen, A. (author)
- Karolinska Inst, Sweden
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- Jansons, J. (author)
- Riga Stradins Univ, Latvia
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- Latyshev, O. E. (author)
- Gamaleja Res Ctr Epidemiol and Microbiol, Russia; Russian Acad Sci, Russia
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- Kuzmenko, Y. V. (author)
- Russian Acad Sci, Russia
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- Hinkula, Jorma (author)
- Linköpings universitet,Avdelningen för mikrobiologi och molekylär medicin,Medicinska fakulteten,Karolinska Inst, Sweden
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- Abakumov, M. A. (author)
- Pirogov Russian Natl Res Med Univ, Russia; Natl Univ Sci and Technol MISIS, Russia
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- Valuev-Elliston, V. T. (author)
- Russian Acad Sci, Russia
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- Gomelsky, M. (author)
- Karolinska Institutet,Univ Wyoming, WY 82071 USA,Gamaleja Res Ctr Epidemiol and Microbiol, Russia; Russian Acad Sci, Russia; Riga Stradins Univ, Latvia
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- Karpov, V. L. (author)
- Russian Acad Sci, Russia
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- Chiodi, F. (author)
- Karolinska Institutet,Karolinska Inst, Sweden
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- Wahren, B. (author)
- Karolinska Institutet,Karolinska Inst, Sweden
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- Logunov, D. Y. (author)
- Gamaleja Res Ctr Epidemiol and Microbiol, Russia; Russian Acad Sci, Russia
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- Starodubova, E. S. (author)
- Russian Acad Sci, Russia
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- Isaguliants, M. G. (author)
- Gamaleja Res Ctr Epidemiol and Microbiol, Russia; Russian Acad Sci, Russia; Riga Stradins Univ, Latvia
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(creator_code:org_t)
- 2018-05-24
- 2018
- English.
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In: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 8
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https://www.nature.c...
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Abstract
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- DNA vaccines require a considerable enhancement of immunogenicity. Here, we optimized a prototype DNA vaccine against drug-resistant HIV-1 based on a weak Th2-immunogen, HIV-1 reverse transcriptase (RT). We designed expression-optimized genes encoding inactivated wild-type and drug-resistant RTs (RT-DNAs) and introduced them into mice by intradermal injections followed by electroporation. RT-DNAs were administered as single or double primes with or without cyclic-di-GMP, or as a prime followed by boost with RT-DNA mixed with a luciferase-encoding plasmid ("surrogate challenge"). Repeated primes improved cellular responses and broadened epitope specificity. Addition of cyclic-di-GMP induced a transient increase in IFN-gamma production. The strongest anti-RT immune response was achieved in a prime-boost protocol with electroporation by short 100V pulses done using penetrating electrodes. The RT-specific response, dominated by CD4+T-cells, targeted epitopes at aa 199-220 and aa 528-543. Drug-resistance mutations disrupted the epitope at aa 205-220, while the CTL epitope at aa 202-210 was not affected. Overall, multiparametric optimization of RT strengthened its Th2- performance. A rapid loss of RT/luciferase-expressing cells in the surrogate challenge experiment revealed a lytic potential of anti-RT response. Such lytic CD4+ response would be beneficial for an HIV vaccine due to its comparative insensitivity to immune escape.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
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- ref (subject category)
- art (subject category)
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- By the author/editor
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Latanova, A. A.
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Petkov, S.
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Kilpelainen, A.
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Jansons, J.
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Latyshev, O. E.
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Kuzmenko, Y. V.
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show more...
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Hinkula, Jorma
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Abakumov, M. A.
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Valuev-Elliston, ...
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Gomelsky, M.
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Karpov, V. L.
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Chiodi, F.
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Wahren, B.
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Logunov, D. Y.
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Starodubova, E. ...
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Isaguliants, M. ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Microbiology in ...
- Articles in the publication
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Scientific Repor ...
- By the university
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Linköping University
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Karolinska Institutet