PMID- 25786238
OWN - NLM
STAT- MEDLINE
DCOM- 20160204
LR  - 20231111
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 3
DP  - 2015
TI  - Design and evaluation of optimized artificial HIV-1 poly-T cell-epitope 
      immunogens.
PG  - e0116412
LID - 10.1371/journal.pone.0116412 [doi]
LID - e0116412
AB  - A successful HIV vaccine in addition to induction of antibody responses should 
      elicit effective T cell responses. Here we described possible strategies for 
      rational design of T-cell vaccine capable to induce high levels of both CD4+ and 
      CD8+ T- cell responses. We developed artificial HIV-1 polyepitope T-cell 
      immunogens based on the conserved natural CD8+ and CD4+ T cell epitopes from 
      different HIV-1 strains and restricted by the most frequent major human leukocyte 
      antigen (HLA) alleles. Designed immunogens contain optimized core polyepitope 
      sequence and additional "signal" sequences which increase epitope processing and 
      presentation to CD8+ and CD4+ T-lymphocytes: N-terminal ubiquitin, N-terminal 
      signal peptide and C-terminal tyrosine motif of LAMP-1 protein. As a result we 
      engineered three T cell immunogens - TCI-N, TCI-N2, and TCI-N3, with different 
      combinations of signal sequences. All designed immunogens were able to elicit 
      HIV-specific CD4+ and CD8+ T cell responses following immunization. Attachment of 
      either ubiquitin or ER-signal/LAMP-1 sequences increased both CD4+ and CD8+ 
      mediated HIV-specific T cell responses in comparison with polyepitope immunogen 
      without any additional signal sequences. Moreover, TCI-N3 polyepitope immunogen 
      with ubiquitin generated highest magnitude of HIV-specific CD4+ and CD8+ T cell 
      responses in our study. Obtained data suggests that attachment of signal 
      sequences targeting polyepitope immunogens to either MHC class I or MHC class II 
      presentation pathways may improve immunogenicity of T-cell vaccines. These 
      results support the strategy of the rational T cell immunogen design and 
      contribute to the development of effective HIV-1 vaccine.
FAU - Reguzova, Alena
AU  - Reguzova A
AD  - State Research Center of Virology and Biotechnology "Vector", Koltsovo, 
      Novosibirsk region, 630559, Russia.
FAU - Antonets, Denis
AU  - Antonets D
AD  - State Research Center of Virology and Biotechnology "Vector", Koltsovo, 
      Novosibirsk region, 630559, Russia.
FAU - Karpenko, Larisa
AU  - Karpenko L
AD  - State Research Center of Virology and Biotechnology "Vector", Koltsovo, 
      Novosibirsk region, 630559, Russia.
FAU - Ilyichev, Alexander
AU  - Ilyichev A
AD  - State Research Center of Virology and Biotechnology "Vector", Koltsovo, 
      Novosibirsk region, 630559, Russia.
FAU - Maksyutov, Rinat
AU  - Maksyutov R
AD  - State Research Center of Virology and Biotechnology "Vector", Koltsovo, 
      Novosibirsk region, 630559, Russia.
FAU - Bazhan, Sergei
AU  - Bazhan S
AD  - State Research Center of Virology and Biotechnology "Vector", Koltsovo, 
      Novosibirsk region, 630559, Russia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150318
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (AIDS Vaccines)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Vaccines, Synthetic)
SB  - IM
MH  - AIDS Vaccines/genetics/*immunology
MH  - Animals
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Epitopes, T-Lymphocyte/genetics/*immunology
MH  - Female
MH  - HEK293 Cells
MH  - HIV-1/genetics/*immunology
MH  - Histocompatibility Antigens Class I/immunology
MH  - Histocompatibility Antigens Class II/immunology
MH  - Humans
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Vaccines, Synthetic/genetics/immunology
PMC - PMC4364888
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/03/19 06:00
MHDA- 2016/02/05 06:00
PMCR- 2015/03/18
CRDT- 2015/03/19 06:00
PHST- 2014/08/17 00:00 [received]
PHST- 2014/12/09 00:00 [accepted]
PHST- 2015/03/19 06:00 [entrez]
PHST- 2015/03/19 06:00 [pubmed]
PHST- 2016/02/05 06:00 [medline]
PHST- 2015/03/18 00:00 [pmc-release]
AID - PONE-D-14-37002 [pii]
AID - 10.1371/journal.pone.0116412 [doi]
PST - epublish
SO  - PLoS One. 2015 Mar 18;10(3):e0116412. doi: 10.1371/journal.pone.0116412. 
      eCollection 2015.