Using the HVTN model to conduct HIV vaccine clinical trials Xia Jin, MD, PhD Chief, Viral Disease and Vaccine Translational Research Unit Executive Director, Vaccine Center Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China. [email protected] 1 st APACC, Hong Kong, May 18, 2016
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Using the HVTN model to conduct HIV vaccine clinical trials
Xia Jin, MD, PhD
Chief, Viral Disease and Vaccine Translational Research Unit
Executive Director, Vaccine Center
Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China. [email protected]
1st APACC, Hong Kong, May 18, 2016
Outline
The structure and governance of HVTN
Recent studies completed through HVTN
• Meta analysis of HIV DNA vaccines
• The outcome of heterologous prime-and-boost immunization
The potential for forming an Asia Pacific Clinical Trials Network
HVTN: HIV Vaccine Trials Network
US sites International sites
Specific study sites Core labs
World’s largest organization to conduct HIV vaccine clinical trials
9 10
12 4
HVTN governance
Leadership
Science
Operations
HVTN accomplishment
Kublin et al., Clin Investig (Lond). 2012
• 1999 – 2012
• 57 trials, 13,000 participants
Recent publications, https://www.hvtn.org
• 2016: 15
• 2015: 29
The immunogenicity of DNA vaccine in humans
10 Trials, 1280 subjects
Gender affects HIV-specific CD4+ T-cell response rates
Jin X*, Morgan C*, Yu X*, et al. Vaccine. 2015 May 11;33(20):2347-53.
BMI affects HIV-specific CD4+ T cell responses
Jin X*, Morgan C*, Yu X*, et al. Vaccine. 2015 May 11;33(20):2347-53.
Multivariate logistic regression analysis confirms the Gender & BMI effects
Jin X*, Morgan C*, Yu X*, et al. Vaccine. 2015 May 11;33(20):2347-53.
DNA vaccines did not elicit strong humoral immune response
Binding antibody response Neutralizing antibody response
Jin X*, Morgan C*, Yu X*, et al. Vaccine. 2015 May 11;33(20):2347-53.
Conclusions
DNA vaccines activated more CD4+ T cells than CD8+ T cells (60-70% vs. 25-40% subjects)
DNA vaccines were inadequate at stimulating antibody responses
Female gender & lower BMI associated with statistically higher HIV-specific CD4+ T-cell response rates
Jin X*, Morgan C*, Yu X*, et al. Vaccine. 2015 May 11;33(20):2347-53.
How to improve the magnitude, breadth and depth of T cell response?
HVTN-083 study design
Primary objective:
– To evaluate heterologous-insert prime-boost
– Clade A env, clade B env
Secondary objective
– To evaluate heterologous vectors prime-boost
– Ad5 + Ad5 vs. Ad35 + Ad35 vs. Ad35 + Ad5
Heterologous insert groups had higher response rate to EnvB (ELISPOT)
Non-responders
Responders
ELISPOT: day 112(4 weeks after 2nd vaccination; n= 168 evaluable subjects
78 ELISPOT responders were assayed by ICS
Heterologous insert groups had higher response rate to EnvB (ICS)
Epitope mapping using overlapping EnvA and EnvB peptides
Heterologous vector groups have a broader T cell response
Mean number of epitopes recognized: 1.38
Heterologous vector groups have a higher magnitude of T cell response
Heterologous insert groups have more response to EnvB and shared epitopes
Heterologous insert groups have more depth in T cell response
Coverage of LANL database sequences is higher for heterologous insert groups
Antibody responses
Binding Abs are similar amonggroups
Neut. Abs are better with homologous insert
Conclusions
Heterologous vector groups had higher numbers of total epitopes
Heterologous insert groups had higher numbers of shared epitopes
These epitopes were highly conserved and led to better theoretical coverage of circulating strains
Opportunities for an APACC network: ACTH
Australia
– Advanced in science and technology
China
– Large
– Rapid growth
Thailand
– International clinical trial experience
Hong Kong
– Business and information center
A
C
T H
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