Science and Technology Daily 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 in human history for 37 years 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 III 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 repeated failures shows that HIV vaccine design 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 from vaccine-focused drugs.
"The replicating vector is a live virus, which will reproduce in the body for a period of time after vaccination. This will not only continuously stimulate the immune system, but also the natural virus attack familiar to the immune system, thereby inducing a stronger and longer-lasting immune response." Shao Yiming said, This new immunization strategy is conducive to a long-term battle against chronic viral infections such as HIV, which has a long incubation period (8-10 years). Traditional and conventional vaccine technologies are only effective against acute viral infections such as the new coronavirus (the incubation period is 1-2 weeks). effective.
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 replication 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 type of vaccine or are in the process of a phase.
China's HIV 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 been fighting HIV for decades, understands that "nuclear" must be "highly imitated" HIV and reformed to stimulate effective immune protection.
The biggest challenge is "high imitation."
Shao Yiming decided to jump out of HIV and look for clues in lentiviruses of the same family and genus.
In 2001, Shao Yiming was lucky enough 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 Transfection (EIAV), and obtained the Equine Transfection (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 modification of HIV immunogens, including determining which glycosylation sites to delete, and which protein conformational structure to modify... "refine".
"The antibodies produced by immunized animals can not only effectively neutralize HIV strains of the same type as the vaccine immunogen, but also neutralize different HIV strains to produce 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 HIV vaccine jointly developed by China CDC and Sinopharm Zhongsheng Group will be very low, less than one yuan per dose." Shao Yiming said that the current high-risk areas for AIDS are developing countries, and vaccine research is necessary at the beginning For application considerations, 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 phases of clinical trials. Volunteers in the high-dose group all had antibody responses against HIV. Two-thirds of the volunteers also had cellular immune responses. No serious adverse events were found. The vaccine is safe. .
"We started the research sample testing and preliminary data analysis ahead of time. Next year, we only need to add the final follow-up data results as planned to unblind and complete the final data analysis. While submitting the research report, we also submitted the Phase III clinical application. Shao Yiming said that the third phase of the clinical trial will answer the question of the vaccine protection rate. After approval, a large-scale clinical trial 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, due to the technical complementarity between the CDC replicating poxvirus vector vaccine and the replicating poxvirus vector vaccine of the National Institutes of Health, China and the United States signed an agreement to carry out joint clinical trials of HIV 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.
Extension link
"Twists and turns" in AIDS vaccine development
The new crown vaccine has three phases of good data in less than a year. Why does the AIDS vaccine always "break down" halfway?
"The evolution of the human immune system has outperformed some viruses, and has lost to others, mainly those newly emerged viruses, such as HIV." Shao Yiming prefers to describe these two camps as "a twin city of viruses." "The former vaccine only needs to follow the traditional vaccine development route and use natural antigens to remind the immune system (vaccination) in advance, and the human body can effectively resist, while HIV belongs to the latter, and cannot use the "short, flat and fast" method to obtain effective resistance. .
Internationally, over the past 30 years, every 10 years has been a generation, carrying out "one twists and turns" of HIV vaccine research.
"This is a process of understanding from the shallower to the deeper. At the beginning, Vaxgen applied the technical route of hepatitis B vaccine to develop a vaccine against HIV outer membrane protein, mainly to stimulate antibody immunity, and it failed in the third phase of clinical trials." Shao Yiming said The second-generation vaccine attempts to target cellular immunity. Compared with the placebo group, the vaccine group also increases the risk of HIV infection; the third-generation vaccine "cocktail" immunity induces stronger antibodies and cellular immunity.
At present, the fastest progress is the combined immunization of poxvirus vector and protein vaccine. Its phase III clinical trial in Thailand showed a protection rate of 31%, but the second phase III clinical trial repeated in Africa was ineffective. It was declared a failure in February this year.
Is there no solution to AIDS vaccine development?
Shao Yiming said that only exploring new technologies and new methods that are different from traditional vaccines and conventional technologies can be the stone of the other mountain for conquering the city B virus vaccine such as HIV.
In fact, based on conservative ideas and commercial reasons, a very suitable HIV vaccine technology route—replicating live virus vector technology—was prematurely abandoned internationally.