East meets West for vaccine design

Today was the last day of the first conference on vaccine design organized by Cold Spring Harbor (CSH) Asia, the Asian branch of the renowned Cold Spring Harbor conference in the state of New York. The gathering took place from June 3 to 7 at a brand new conference center and hotel built in 2010 in Suzhou, just one hour by car (half an hour by the recently constructed high speed train) from Shanghai. The center was built for CSH Asia to hold such meetings, said Maoyen Chi, who directs the CSH Asia program. So far, CSH Asia has held almost 40 meetings here, covering many areas of biology.

Given China’s rapid economic development, many Chinese scientists trained in the West are now coming back, Chi said, and the CSH Asia conference center was established to meet the resulting demand for high level academic conferences in the area. “We try to create a common platform for all the scientists [in] the entire Asia-Pacific region,” he said, adding that the local Suzhou government invested in the project to increase the international visibility of Suzhou Industrial Park, an economic and technological cooperation between the governments of China and Singapore. “There is hope that somebody develops biotech companies,” Chi said. “This is a high tech hub.” 

And the area is still growing: From my hotel window, I can see several high rise buildings going up, swarmed by about a dozen cranes. Research funding by the Chinese government has been rising as well, said Lubin Jiang, a malaria researcher who returned to China last year after an eight-year postdoctoral stint at the NIAID, to start his own lab at the Institute Pasteur of Shanghai. Jiang said he decided to come back because he received a more attractive offer from China than from the US. 

Still, not everything is better in China: For example, some attendees told me that many internet sites are regularly blocked or slowed down by the government. In addition to popular sites like Facebook, the affected sites also include ones that are important for researchers such as Pubmed, a major scientific publication search engine. 

The conference attracted about 60 attendees, about half of whom are based in Asia. The talks spanned a range of vaccine approaches, mostly to HIV, but also to other pathogens such as the malaria parasite, Dengue virus, salmonella, influenza, herpes, and hepatitis C virus. 

As for HCV, David Klatzmann of the Université Pierre et Marie Curie in Paris described a virus like particle (VLP) based approach to vaccine design. It is the first, he said, to induce broadly neutralizing HCV-specific antibodies in macaques. Next, Klatzmann plans to do clinical safety trials in China, where up to 100 million people might be infected with HCV. Klatzmann said he also observed good immune responses in animals vaccinated with HIV antigens carried by his VLPs. 

The use of adenoviruses as vaccine vectors was also discussed. Given the failures of two major clinical AIDS vaccine trials that involve adenovirus serotype 5 (Ad5) as vectors—Merck’s Step trial as well as HVTN 505—there is currently not much enthusiasm for the use of such vectors. One concern is that many people have preexisting immune responses to some adenoviruses auch as Ad5, which could reduce vaccine responses and/or help induce additional HIV target cells as a result of vaccination.

But Ling Chen, who was involved in the development of the Step trial vaccine while at Merck and is now at the Guangzhou Institute of Biomedicine and Health in Guangzhou, China, presented an approach that circumvents the issue of preexisting immunity. The trick is to take white blood cells from a vaccine recipient, infect them with the adenovirus-based vaccine, wash off any free adenovirus particles, and then reinfuse the infected cells back into the individual. This way, the reinfused cells express the antigens carried by the adenovirus without directly exposing the vaccinee to the adenovirus particles. 

Already, Chen said, he has promising results that suggest that vaccinating macaques this way can induce similar SIV-specific immune responses in animals with preexisting immune responses as in animals without such responses. Compared with animals vaccinated with Ad5 particles directly, the reinfused animals had similar SIV-specific, but lower Ad5-specific responses. 

Linqi Zhang from Tsinghua University in Beijing, one of the organizers of the meeting, presented an approach to measure the targets of the antibody responses in HIV-infected people. He expressed a library of HIV-1 target proteins on the surface of yeast cells. Using a number of experimental tricks, he said he was even able to express antibody targets that consist of parts of a protein that are normally far apart in the actual protein sequence and are only brought together because of the way the protein folds (so-called conformational epitopes). 

When Zhang used this approach to analyze sera of HIV-infected individuals, he found that the initial antibody responses mostly target gp41, while the later emergence of gp120-specific responses correlated with the appearance of antibodies that could neutralize the virus that initially infected the individual. To Zhang, this suggests that gp41 is a decoy that distracts the immune system and should not be included in vaccine candidates. 

With just 60 participants, the meeting was quite small. That was good thing because it left more time for questions and discussion after the talks, said co-organizer Michael Good from Griffith University in Southport, Australia. But others wished there had been more. “I hope they can recruit more people” next time, said Jiang. 

Since everything else in China seems to be growing, the next meeting may well have many more attendees.