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HIVIS-DNA or HIVISopt-DNA priming followed by CMDR vaccinia-based boosts induce both humoral and cellular murine immune responses to HIV.
Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Department of Microbiology Tumor and Cell Biology, Karolinska Institutet, 17177 Stockholm, Sweden.
Department of Microbiology Tumor and Cell Biology, Karolinska Institutet, 17177 Stockholm, Sweden.
Department of Microbiology Tumor and Cell Biology, Karolinska Institutet, 17177 Stockholm, Sweden.
Department of Microbiology Tumor and Cell Biology, Karolinska Institutet, 17177 Stockholm, Sweden.
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2017 (English)In: Heliyon, ISSN 2405-8440, Vol. 3, no 6, article id e00339Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: In order to develop a more effective prophylactic HIV-1 vaccine it is important optimize the components, improve Envelope glycoprotein immunogenicity as well as to explore prime-boost immunization schedules. It is also valuable to include several HIV-1 subtype antigens representing the world-wide epidemic.

METHODS: HIVIS-DNA plasmids which include Env genes of subtypes A, B and C together with Gag subtypes A and B and RTmut/Rev of subtype B were modified as follows: the Envelope sequences were shortened, codon optimized, provided with an FT4 sequence and an immunodominant region mutated. The reverse transcriptase (RT) gene was shortened to contain the most immunogenic N-terminal fragment and fused with an inactivated viral protease vPR gene. HIVISopt-DNA thus contains fewer plasmids but additional PR epitopes compared to the native HIVIS-DNA. DNA components were delivered intradermally to young Balb/c mice once, using a needle-free Biojector® immediately followed by dermal electroporation. Vaccinia-based MVA-CMDR boosts including Env gene E and Gag-RT genes A were delivered intramuscularly by needle, once or twice.

RESULTS: Both HIVIS-DNA and HIVISopt-DNA primed humoral and cell mediated responses well. When boosted with heterologous MVA-CMDR (subtypes A and E) virus inhibitory neutralizing antibodies were obtained to HIV-1 subtypes A, B, C and AE. Both plasmid compositions boosted with MVA-CMDR generated HIV-1 specific cellular responses directed against HIV-1 Env, Gag and Pol, as measured by IFNγ ELISpot. It was shown that DNA priming augmented the vector MVA immunological boosting effects, the HIVISopt-DNA with a trend to improved (Env) neutralization, the HIVIS-DNA with a trend to better (Gag) cell mediated immune reponses.

CONCLUSIONS: HIVIS-DNA was modified to obtain HIVISopt-DNA that had fewer plasmids, and additional epitopes. Even with one DNA prime followed by two MVA-CMDR boosts, humoral and cell-mediated immune responses were readily induced by priming with either DNA construct composition. Priming by HIV-DNA augmented neutralizing antibody responses revealed by boosting with the vaccinia-based heterologous sequences. Cellular and antibody responses covered selected strains representing HIV-1 subtypes A, B, C and CRF01_AE. We assume this is related to the inclusion of heterologous full genes in the vaccine schedule.

Place, publisher, year, edition, pages
Elsevier, 2017. Vol. 3, no 6, article id e00339
Keywords [en]
Immunology, Infectious disease, Vaccines, Virology
National Category
Microbiology in the medical area
Identifiers
URN: urn:nbn:se:liu:diva-141182DOI: 10.1016/j.heliyon.2017.e00339PubMedID: 28721397Scopus ID: 2-s2.0-85021324793OAI: oai:DiVA.org:liu-141182DiVA, id: diva2:1144184
Available from: 2017-09-25 Created: 2017-09-25 Last updated: 2018-01-13Bibliographically approved

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