A novel replication-competent modified vaccinia Tiantan (MVTT)-based HIV Vaccine
3
www.aids2014.org A novel replication-competent modified vaccinia Tiantan (MVTT)- based HIV Vaccine Haibo Wang 1, 2 , Linqi Zhang 3 and Zhiwei Chen 1 1 AIDS Institute, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, PR. China; 2 Zhuhai International Travel Healthcare Center, Zhuhai, 519020, PR China; 3 Comprehensive AIDS Research Center and Research Center for Public Health, School of Medicine, Tsinghua University, Beijing, 100084, PR China Advantages of MVTT: Patented live replicating viral vector (Virology 2005); Immunogenic than MVA (PLoS One 2009); Highly attenuated and safe in SCID mice (Vaccine 2010); Protective immunity ( JVI 2013). Problems: Instability of foreign genes; Screening process.
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A novel replication-competent modified vaccinia Tiantan (MVTT)-based HIV Vaccine Haibo Wang 1, 2 , Linqi Zhang 3 and Zhiwei Chen 1 1 AIDS Institute, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, PR. China; - PowerPoint PPT Presentation
Transcript of A novel replication-competent modified vaccinia Tiantan (MVTT)-based HIV Vaccine
www.aids2014.org
A novel replication-competent modified vaccinia Tiantan (MVTT)-based HIV Vaccine
Haibo Wang1, 2, Linqi Zhang3 and Zhiwei Chen1
1 AIDS Institute, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, PR. China;2 Zhuhai International Travel Healthcare Center, Zhuhai, 519020, PR China; 3 Comprehensive AIDS Research Center and Research Center for Public Health, School of Medicine, Tsinghua University, Beijing, 100084, PR China
Advantages of MVTT:
Patented live replicating viral vector (Virology 2005);Immunogenic than MVA (PLoS One 2009);Highly attenuated and safe in SCID mice (Vaccine 2010);Protective immunity (JVI 2013).
Problems:
Instability of foreign genes;Screening process.
www.aids2014.org
env gag-pol
p1F
p1R
p2F
p2R
p3F
p3R
p4F
p4R
1 2 3 4 5 6 7 8 9 10 11 12 13 14
Template: 1,4,8,12 MVTTHKU-gpe/AE13; 2,5,9,13 MVTT; 3,6,10,14 Blank.Lane 1-3: primer set 1, indicating the large deletion site on the genome.Lane 4-6: primer set 2, indicating the insertion of env.Lane 8-10: primer set 3, indicating the insertion of gag.Lane 12-14: primer set 4, indicating the insertion of pol.
A
In vitro characterization
MVTT MVTTHKU-gpe/AE13
CB
MVTT M MVTTHKU-gpe/AE13
Gag-polEnv
Pol
Gag
100
101
102
103
104
105
106
107
108
0 24 48 72
Vir
us
Tite
r (P
FU
/ml)
Time post infection (hrs)
D
E
P1 P6
www.aids2014.org
In vivo characterization
Conclusion
0 3 6 9 12 15 18 21-70-60-50-40-30-20-10
0102030
Wei
ght c
hang
e, %
Days after inoculation
PBS MVTT
HKU-gpe/AE13 I.M.
MVTTHKU
-gpe/AE13 I.L.
A
I.M. I.L.100
101
102
103
104
105
106
anti-
env
antib
ody
titer
IgG1 IgG2a
B
We have constructed a novel MVTT-based HIV vaccine to express env and gag-pol genes of HIVCRF01_AE. This vaccine remains replication-competent with excellent transgene stability. The vaccine displays satisfactory safety and immunogenicity profiles in small animals. Non-human primates studies and human trials have been planned to further characterize its immunogenicity. Given the success (although modest) of RV144 trial, we believe this novel replication-competent modified vaccinia
Tiantan-based vaccine will play a key role during the combating of HIV/AIDS pandemic.
We thank HK-RGC762811, HKU-UDF and China’s Mega Project 2012ZX10001-009 for support.
