PMID- 26076321
OWN - NLM
STAT- MEDLINE
DCOM- 20160419
LR  - 20181113
IS  - 2164-554X (Electronic)
IS  - 2164-5515 (Print)
IS  - 2164-5515 (Linking)
VI  - 11
IP  - 7
DP  - 2015
TI  - Effects of the fusion design and immunization route on the immunogenicity of 
      Ag85A-Mtb32 in adenoviral vectored tuberculosis vaccine.
PG  - 1803-13
LID - 10.1080/21645515.2015.1042193 [doi]
AB  - Vaccines containing multiple antigens may induce broader immune responses and 
      provide better protection against Mycobacterium tuberculosis (Mtb) infection as 
      compared to a single antigen. However, strategies for incorporating multiple 
      antigens into a single vector and the immunization routes may affect their 
      immunogenicity. In this study, we utilized recombinant adenovirus type 5 (rAd5) 
      as a model vaccine vector, and Ag85A (Rv3804c) and Mtb32 (Rv0125) as model 
      antigens, to comparatively evaluate the influence of codon usage optimization, 
      signal sequence, fusion linkers, and immunization routes on the immunogenicity of 
      tuberculosis (TB) vaccine containing multiple antigens in C57BL/6 mice. We showed 
      that codon-optimized Ag85A and Mtb32 fused with a GSG linker induced the 
      strongest systemic and pulmonary cell-mediated immune (CMI) responses. Strong CMI 
      responses were characterized by the generation of a robust IFN-gamma ELISPOT response 
      as well as antigen-specific CD4(+) T and CD8(+) T cells, which secreted mono-, 
      dual-, or multiple cytokines. We also found that subcutaneous (SC) and intranasal 
      (IN)/oral immunization with this candidate vaccine exhibited the strongest 
      boosting effects for Mycobacterium bovis bacille Calmette-Guerin (BCG)-primed 
      systemic and pulmonary CMI responses, respectively. Our results supported that 
      codon optimized Ag85A and Mtb32 fused with a proper linker and immunized through 
      SC and IN/oral routes can generate the strongest systemic and pulmonary CMI 
      responses in BCG-primed mice, which may be particularly important for the design 
      of TB vaccines containing multiple antigens.
FAU - Zhang, Yiling
AU  - Zhang Y
AD  - a State Key Laboratory of Respiratory Diseases; The First Affiliated Hospital of 
      Guangzhou Medical University ; Guangzhou , China.
FAU - Feng, Liqiang
AU  - Feng L
FAU - Li, Liang
AU  - Li L
FAU - Wang, Dimin
AU  - Wang D
FAU - Li, Chufang
AU  - Li C
FAU - Sun, Caijun
AU  - Sun C
FAU - Li, Pingchao
AU  - Li P
FAU - Zheng, Xuehua
AU  - Zheng X
FAU - Liu, Yichu
AU  - Liu Y
FAU - Yang, Wei
AU  - Yang W
FAU - Niu, Xuefeng
AU  - Niu X
FAU - Zhong, Nanshan
AU  - Zhong N
FAU - Chen, Ling
AU  - Chen L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hum Vaccin Immunother
JT  - Human vaccines & immunotherapeutics
JID - 101572652
RN  - 0 (BCG Vaccine)
RN  - 0 (Cytokines)
RN  - 0 (Tuberculosis Vaccines)
RN  - 0 (Vaccines, Synthetic)
SB  - IM
MH  - Adenoviridae/*genetics
MH  - Administration, Oral
MH  - Animals
MH  - BCG Vaccine/immunology
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Cytokines/metabolism
MH  - Female
MH  - Genetic Vectors
MH  - Immunity, Cellular
MH  - Lung/immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Spleen/immunology
MH  - Tuberculosis Vaccines/administration & dosage/*genetics/*immunology
MH  - Vaccines, Synthetic/administration & dosage/*genetics/*immunology
PMC - PMC4514253
OTO - NOTNLM
OT  - APC, Allophycocyanin
OT  - BCG, Mycobacterium bovis bacille Calmette-Guerin
OT  - BSA, bovine serum album
OT  - CMI, cell-mediated immune responses
OT  - DAPI, 4',6-diamidino-2-phenylindole
OT  - DMSO, Dimethyl sulfoxide
OT  - ELISPOT, Enzyme-linked immune-sorbent spot
OT  - FACS, Fluorescence Activated Cell Sorter
OT  - FBS, fetal bovine serum
OT  - FITC, fluorescein isothiocyanate
OT  - HA tag, hemagglutinin tag
OT  - HEK, human embryo kidney
OT  - ICS, Intracellular cytokine staining
OT  - IFN-gamma, interferon gamma
OT  - IL-2, Interleukin 2
OT  - IM, intramuscular
OT  - IN, intranasal
OT  - Mtb, Mycobacterium tuberculosis
OT  - NBT/BCIP, Nitro blue tetrazolium/ 5-Bromo-4-chloro-3-indolyl phosphate
OT  - PBS, Phosphate Buffered Saline
OT  - PCR, polymerase chain reaction
OT  - PE, Phycoerythrin
OT  - PerCP, Peridinin-ChlorophylL-Protein Complex
OT  - RPMI, Roswell Park Memorial Institute
OT  - SC, subcutaneous
OT  - SDS-PAGE, sodium dodecyl sulfate polyacrylamide gel electrophoresis
OT  - SFC, spot-forming cells
OT  - TB, tuberculosis
OT  - TNF-alpha, tumor necrosis factor alpha
OT  - fusion strategies
OT  - immunization routes
OT  - immunogenicity
OT  - multiple antigens
OT  - mycobacterium tuberculosis
OT  - rAd5, recombinant adenovirus type 5
OT  - tPA, tissue plasminogen activator
OT  - vp, viral particles
EDAT- 2015/06/16 06:00
MHDA- 2016/04/20 06:00
PMCR- 2016/06/15
CRDT- 2015/06/16 06:00
PHST- 2015/06/16 06:00 [entrez]
PHST- 2015/06/16 06:00 [pubmed]
PHST- 2016/04/20 06:00 [medline]
PHST- 2016/06/15 00:00 [pmc-release]
AID - 1042193 [pii]
AID - 10.1080/21645515.2015.1042193 [doi]
PST - ppublish
SO  - Hum Vaccin Immunother. 2015;11(7):1803-13. doi: 10.1080/21645515.2015.1042193.