“If the vaccine works on humans the implications are enormous,” says Dr Chen. “Not only a giant leap towards preventing and treating Human Immunodeficiency Virus (HIV) infection – but also for designing vaccines for other diseases such as cancer.”
So far the vaccine, which induces a high frequency of the CD8⁺ T cells – whose function is to eliminate HIV-infected cells – has proven highly effective on mice, and Dr Chen and his team are now seeking funding for testing in larger animals and then humans. “We worked to provide a proof of concept using mice, aiming to see whether we could use a specific antigen design for the vaccine, to elicit a strong host immunity,” he says. “That study has already obtained an international patent, signifying that HKU researchers have the capability to invent novel AIDS vaccines.”
The study is led by Dr Chen Zhiwei, Director of HKU’s AIDS Institute (centre), and other key researchers including Dr Allen Cheung Ka-loon, Post-doctoral Fellow (right) and Ms Zhou Jingying, a final-year PhD candidate (left).
Before coming to HKU Dr Chen worked at the Aaron Diamond AIDS Research Center (ADARC) [affiliated with Rockefeller University] with renowned scientist Dr David Ho, Scientific Director and Chief Executive Officer of ADARC, inventing two kinds of vaccine – vector-based and DNA-based – which then proceeded to human testing. “With the human data generated, we realised both vaccines were very safe and both were immunogenic, but they were not as strong as we initially expected.”
At that time a regulatory molecule – called the PD1 – was discovered to interact with dendritic cells, which is related to the function of CD8⁺ T cells. Dr Chen and his team in Hong Kong have been able to find a way to use PD1 as a tool to enhance the process of transferring antigen via dendritic cells which has resulted in far higher levels of qualitatively enhanced and long-lasting HIV specific CD8⁺ T cells for killing and removing virus-infected cells.
Using mice, Dr Chen did a viral challenge study to evaluate its efficacy as a preventive vaccine. At the same time he generated a cancer model, aiming to see whether this kind of T-cell could eliminate cancer cells. Significantly, the results showed if high levels of CD8⁺ T cells were present, they could eliminate most HIV-infected cells or a cancer cell carrying the HIV protein. Part of the research has been published in the Journal of Clinical Investigation.
The team has discovered that a specific molecule on dendritic cells can induce a high frequency of CD8⁺ T cells, and hence is a breakthrough in creating a novel AIDS vaccine for AIDS prevention and treatment.
My dream is that we can use this technology to make effective multivirulent vaccines for human use – against different types of Human Immunodeficiency Virus (HIV) in the same vaccine, perhaps HIV and tuberculosis in another.
Dr Chen Zhiwei
Potent and effective
“We are at a stage where we feel confident about the uniqueness of this vaccination. Not just the different types of immunity we elicited but the quality in terms of killing the virus of the cells and also the cancer cells – it is rather potent and very effective.”
The findings have implications not only for HIV, and cancer, but also pathogens like malaria and tuberculosis (TB). “For all these diseases you need to elicit a high level of CD8⁺ T cells,” says Dr Chen. “In the paper we discuss the potential for developing a way to specifically elicit a high level of CD8⁺ T cells, not just against HIV, but maybe different types of antigen that would make this technique very useful for future disease prevention and for immunotherapy.”
He is now seeking funding for and investment in the research. The regular Research Grants Council (RGC) funding is not enough: “The RGC General Research Fund HK$1 million is not even enough to produce this type of vaccine for human testing,” he says. “We calculate testing the vaccine on humans in China would cost close to HK$30 million.”
And there’s the rub. “Under Hong Kong’s current mechanism, there is no structure to support research institutions, nor to maintain a team of well-trained doctors for long-term research development.”
He feels this is leading to wasted opportunities – for Hong Kong and for HKU: “There are so many excellent discoveries made in the Faculty of Medicine each year, but what percentage actually make it into daily human use? The Hong Kong Government needs to address this.”
In the meantime, to help draw global attention to his discovery and to foster potential collaborations, the AIDS Institute recently co-directed an HIV course and a public lecture, attended by international experts, including Nobel Prize-winner Professor Françoise Barré-Sinoussi.
Nobel laureate Professor Françoise Barré-Sinoussi speaking at an AIDS Institute public lecture this summer
“My dream,” says Dr Chen, “is that we can use this technology to make effective multivirulent vaccines for human use – against different types of HIV in the same vaccine, perhaps HIV and TB in another. Then, I’ll call it a breakthrough.”■