Question: What is the "winning chance" of China's AIDS vaccine?
Our reporter Zhang Jiaxing
Recently, some media reported that China’s AIDS vaccine will apply for Phase III clinical trials next year.
One stone stirred up a thousand waves.
The AIDS vaccine has been developed for 37 years in human history since its inception. Hundreds of clinical trials have ended in failure. What is the chance of success for China’s AIDS vaccine that may start a phase three clinical trial next year?
On December 17, a reporter from Science and Technology Daily went to the Chinese Center for Disease Control and Prevention of STDs and AIDS Prevention and Control Center to interview Professor Shao Yiming, the head of the R&D team and the chief expert on AIDS at the Chinese Center for Disease Control and Prevention.
You are brave! Chinese team uses replicating live virus vector
The experience of continuous failure shows that the design of an AIDS vaccine must be courageous and strategic.
At the end of the last century, Shao Yiming learned that only two phase I clinical trials of replicating poxvirus vector AIDS vaccines had been carried out internationally, and then they were discontinued.
At that time, the CDC AIDS vaccine team led by Shao Yiming had selected replicating viral vectors to carry out the Phase I clinical trial of AIDS vaccine research, and the results showed good safety.
Shao Yiming went to the United States to find scientists who were engaged in these two trials to ask about the reasons, and learned that the termination of the research was not due to technical reasons, but the commercial decision of pharmaceutical companies to withdraw vaccine drugs.
"The replicating vector is a live virus. After vaccination, it will reproduce in the body for a period of time. This will not only continue to stimulate the immune system, but also make the immune system familiar with the natural virus attack, thereby inducing a stronger and longer-lasting immune response." Shao Yiming said. This new immunization strategy is conducive to fighting the “protracted war” against chronic viral infections such as HIV, which has a long incubation period (8-10 years). Traditional and conventional vaccine technologies only fight against acute viral infections such as the new coronavirus (incubation period 1— 2 weeks) is valid.
It is generally believed that replicating live vectors are not as safe as non-replicating dead vectors, and safety incidents due to poor selection will cause other medical products of multinational pharmaceutical companies to be implicated and cause losses. This is the main reason why companies abandon this route.
"The reason why we selected the replicating vaccinia virus'Tiantan strain' with independent intellectual property rights as the AIDS vaccine carrier is because in the smallpox eradication campaign in the last century, it has a history of safe application with the largest number of vaccinated people and the longest time." Shao Yiming said.
In recent years, international research teams have gradually realized the advantages of the replicative vector route and have gradually carried out AIDS vaccine research on this route.
According to statistics from the International AIDS Vaccine Initiative (IAVI), up to now, the United States and other countries have completed a phase of this vaccine or are in the process of a phase.
China's AIDS vaccine has completed Phase I and Phase II clinical trials, ranking first in the process.
Intent! The Chinese team designed a "high imitation of Miao" based on the "genealogy"
If the carrier of the “Tiantan strain” solves the problem of “protracted war”, then the “nucleus” carried by the carrier will determine whether it can “precise strike”.
Shao Yiming, who has struggled with HIV for decades, understands that "nuclear" must be "highly imitated" and modified to stimulate effective immune protection.
The biggest challenge is "high imitation."
Shao Yiming decided to jump out of HIV and look for clues in the lentiviruses of the same family and genus.
In 2001, Shao Yiming was fortunate to find Academician Shen Rongxian of the Harbin Institute of Veterinary Medicine of the Chinese Academy of Agricultural Sciences, who developed the world's first lentiviral vaccine-Equine Transmission (EIAV), and obtained the Equine Transmission (EIAV) live attenuated vaccine.
The team of Shao Yiming and Academician Shen has worked together for more than ten years, and measured the EIAV attenuation process of hundreds of generations of cell culture, and identified the key gene mutations that convert highly pathogenic wild strains into safe and effective vaccine strains.
They then used the techniques of structural biology and bioinformatics to produce a “high-replica” map for the transformation of HIV immunogens, including determining which glycosylation sites to delete and which protein conformational structure to transform... The immunogen is "refined".
"The antibodies produced by stimulating immune animals can not only effectively neutralize HIV strains of the same type as the vaccine immunogen, but also neutralize different HIV strains, producing a broad-spectrum immune protection effect." Shao Yiming said.
It is expected to start Phase III clinical trial next year and obtain vaccine protection effect in 3 years
"The production cost of the replicating virus vector AIDS vaccine jointly developed by China CDC and Sinopharm Zhongsheng Group will be very low, less than 1 yuan per dose." Shao Yiming said that the current high-risk areas for AIDS are developing countries. Must be considered for the application, to avoid "aristocratic".
Up to now, the vaccine has completed the first phase clinical trial at Peking Union Medical College Hospital and the first phase 2 clinical trial at Beijing You'an Hospital.
Currently, the second phase II clinical trial is being carried out in Beijing You'an Hospital and the First Affiliated Hospital of Zhejiang University.
A total of 400 people participated in the above-mentioned phases of clinical trials. Volunteers in the high-dose group were able to develop antibody responses against HIV. 2/3 of the volunteers also had cellular immune responses. No serious adverse event was found. The safety of the vaccine good.
"We started the research sample testing and preliminary data analysis in advance. Next year, we only need to add the final follow-up data results as planned to complete the final data analysis. We submit the application for Phase III clinical trials while submitting the research report." Shao Yiming said, “Phase III clinical trials will answer the question of vaccine protection rate. After approval, large-scale clinical trials will be launched, which is expected to end within 3 years, so as to obtain my country’s self-developed AIDS vaccine immune protection data.”
At the same time, because the CDC replicating poxvirus vector vaccine and the National Institutes of Health's replicating poxvirus vector vaccine are technologically complementary, China and the United States signed an agreement to carry out joint clinical trials of AIDS vaccines between the two countries.
At present, the teams of the two countries are preparing to submit a clinical trial application to the State Food and Drug Administration.