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.
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In vitro characterization
p3F
p2F
p1F
p4F
D
gag-pol
env
p1R
p2R
p3R
8
10
p4R
7
Virus Titer (PFU/ml)
A
10
6
10
5
10
4
10
3
10
2
10
1
10
0
10
1
2
3
4
5
6
7 8
9
10
24
48
Time post infection (hrs)
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.
B
0
E
C
MVTT M MVTTHKU-gpe/AE13
Gag-pol
Env
P1
Pol
Gag
MVTT
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MVTTHKU-gpe/AE13
P6
72
In vivo characterization
B
30
20
10
0
-10
-20
-30
-40
-50
-60
-70
6
PBS
MVTTHKU-gpe/AE13 I.M.
MVTTHKU-gpe/AE13 I.L.
IgG1
IgG2a
10
anti-env antibody titer
Weight change, %
A
5
10
4
10
3
10
2
10
1
10
0
0
3
6 9 12 15 18
Days after inoculation
21
10
I.M.
I.L.
Conclusion
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 Tiantanbased 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.
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