Is it Feasible to Test the Effect of the new corona Vaccine by "Testing the Virus"

According to a recent report by the Financial Times, in order to accelerate the development of the new crown vaccine, the British government will fund the world's first new crown vaccine "human challenge trial" in the country. Volunteers participating in the trial will be artificially infected after being vaccinated with the candidate new crown vaccine New coronavirus to test the effect of the vaccine. Although there have been many precedents, the "human challenge test" is still a controversial test method. Volunteers who "test drugs by themselves" need to be isolated and bear certain health risks. Under the dual pressure of the global public health and economic crisis caused by the new corona pandemic, is this unconventional test method feasible? How the experiment is carried out?

The person involved in the project told the Financial Times that the test is expected to be officially launched in January next year. Its academic leader is Imperial College, which is specifically operated by an institution called h vivo . The test site has not yet been finalized. It may be carried out in a quarantine clinic in east London, or another facility nearby. The subject will be vaccinated with the candidate new crown vaccine first, and will receive a "challenging" dose of the new crown virus under controlled conditions about one month later. The isolation period may be as long as one month. According to reports, about 2,000 people have passed the "Human Challenge Test" advocacy organization headquartered in the United States to sign up for the test to be carried out in the UK "One Day Early". In order to prevent subjects from developing serious illnesses after being infected with the virus, this trial will first use the antiviral drug Remdesivir, which has been approved in many countries for the treatment of new coronavirus infections.

The conduct of such trials in the UK must be approved by the UK Medicines and Healthcare Products Administration and an independent research ethics committee. The Financial Times quoted a statement from the UK Medicines and Healthcare Products Administration as saying, “The safety of subjects is our highest priority. Any proposal from (vaccine) developers regarding the challenge of human infection as part of clinical trials for vaccine development , Will be considered on a (weighing) benefit-risk basis, and will monitor and minimize risks in the proposed trial design.”

In vaccine development, the general plan is to evaluate the effectiveness of vaccines through phase 3 clinical trials. Why should the development of new crown vaccines consider the unconventional research method of "human challenge trials"? Some experts believe that the current increase in thousands of new crown deaths worldwide makes vaccine development an extremely urgent task, and "human challenge trials" can greatly speed up the vaccine development process. Claire Waddington, a clinical lecturer in the field of infectious diseases at the University of Cambridge in the United Kingdom, believes: "The advantage of the controlled human infection model is that it allows us to know exactly when people are exposed to relevant pathogens, so that we can directly and accurately study the models used in the model. The response and protection of any vaccine to infection."

In fact, American and British scientists have been discussing or appealing for the implementation of "human challenge tests" in the development of new crown vaccines for several months. Researchers from Rutgers University, Harvard University and other institutions in the United States published an article entitled "Human Challenge Research to Accelerate Coronavirus Vaccine Licensing" in the American Journal of Infectious Diseases in May, saying that the controlled new coronavirus vaccine "human challenge test" It may shorten the time spent on vaccine evaluation and enable the vaccine to be promoted earlier. The article suggests that most of the new crown vaccines can be subject to "human challenge tests" before they are ready to enter the effectiveness test. In addition to evaluating the effectiveness of vaccines, the "human challenge test" also helps to evaluate drugs used to prevent infection before exposure to high-risk individuals, stop infection or prevent the onset of disease after exposure, and enhance the understanding of the relevant mechanisms from infection to disease.

In mid-July, more than 170 American and British scientists, including 15 Nobel Prize winners in science, jointly issued an open letter to Francis Collins, President of the National Institutes of Health, urging the US government to prepare for the "human challenge test", including supporting safety Reliable new coronavirus cultivation and isolation facilities for subjects. Is it against ethics? The history of the "Human Challenge Test" can be traced back to 1796, when the pioneer of vaccine research Edward Jenner vaccinated 8-year-old James Phips with live vaccinia virus. This risky method made the little boy a miracle. Like immunity. Since then, this type of "testing the virus" research has played an active role in developing vaccines and treatments against infectious diseases such as typhoid fever, cholera, and malaria, and understanding how the human immune system responds to viruses such as influenza. Although there have been many precedents, the "human challenge test" is still a highly controversial research method, especially for the new coronavirus, a virus with a certain fatality rate and no specific drugs and treatments. Is it a violation of "testing the virus with the body" Medical ethics?

Researchers from Monash University in Australia published a review article in the British journal "The Lancet Infectious Diseases" in May, saying that when a specific pathogen poses a huge public health threat, especially in the absence of specific treatments and vaccines, this Such research is ethically acceptable. They can accelerate and improve vaccine development, and can limit and reduce the risk of subjects through trial design. The aforementioned article "Human Challenge Research Accelerates Coronavirus Vaccine Licensing" believes that "challenge trials" are based on volunteers' informed consent, minimization of research risks, and subjects with a high baseline risk of infection (risk of infection in normal life). As an emergency response requirement, it does not infringe on the personal rights and interests of subjects, but is a choice made after taking into account personal rights and global public health emergencies.

In response to discussions in the scientific community, the World Health Organization issued the "Key Guidelines for the Ethical Acceptability of New Coronavirus Human Challenge Research" in May, emphasizing that the "human challenge test" of the new coronavirus vaccine must be carried out in accordance with the "highest scientific and ethical" standards, and at least must be followed 8 ethical standards, including that the experiment must have a strong scientific basis, and the public, relevant experts, and decision-makers must participate in consultation to obtain information. Researchers, funders, decision-makers and regulatory agencies must coordinate closely to ensure that the test The screening criteria of the applicants can limit and minimize the risk of the test, and must be reviewed by an independent committee and perform strict informed consent procedures.