Please use this identifier to cite or link to this item:
10.1016/j.heliyon.2017.e00339
Title: | HIVIS-DNA or HIVISopt-DNA priming followed by CMDR vaccinia-based boosts induce both humoral and cellular murine immune responses to HIV |
Authors: | Hinkula, J. Petkov, S. Ljungberg, K. Hallengärd, D. Bråve, A. Isaguliants, M. Falkeborn, T. Sharma, S. Liakina, V. Robb, M. Eller, M. Moss, B. Biberfeld, G. Sandström, E. Nilsson, C. Markland, K. Blomberg, P. Wahren, B. |
Keywords: | Immunology;Infectious disease;Vaccines;Virology;3.1 Basic medicine;3.2 Clinical medicine;1.1. Scientific article indexed in Web of Science and/or Scopus database;General;SDG 3 - Good Health and Well-being |
Issue Date: | 1-Jun-2017 |
Citation: | Hinkula , J , Petkov , S , Ljungberg , K , Hallengärd , D , Bråve , A , Isaguliants , M , Falkeborn , T , Sharma , S , Liakina , V , Robb , M , Eller , M , Moss , B , Biberfeld , G , Sandström , E , Nilsson , C , Markland , K , Blomberg , P & Wahren , B 2017 , ' HIVIS-DNA or HIVISopt-DNA priming followed by CMDR vaccinia-based boosts induce both humoral and cellular murine immune responses to HIV ' , Heliyon , vol. 3 , no. 6 , e00339 . https://doi.org/10.1016/j.heliyon.2017.e00339 |
Abstract: | 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. |
Description: | Funding Information: This work was supported by Doctors against AIDS association, Stockholm , and EU projects Vactrain , EAVI and Epiical . Publisher Copyright: © 2017 The Authors |
DOI: | 10.1016/j.heliyon.2017.e00339 |
ISSN: | 2405-8440 |
Appears in Collections: | Research outputs from Pure / Zinātniskās darbības rezultāti no ZDIS Pure |
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HIVIS_DNA_or_HIVISopt_DNA_priming_followed_by_CMDR.pdf | 1.09 MB | Adobe PDF | View/Open |
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