This article is from the WeChat public account: Nature Nature Research (ID: Nature-Research) , original author: Ewen Callaway, from FIG question: IC photo
The development of a new crown virus vaccine is progressing at a high speed. On March 16, local time, one of the first dozens of healthy volunteers underwent a clinical phase I vaccine safety trial in Seattle. The trial was funded by the US government. Similar safety trials for other coronavirus vaccines will begin soon.
Recently, a COVID-19 coronavirus vaccine candidate has begun clinical trials. Source: Ted S Warren / AP / Shutterstock
Although the first human trial has been started, there are still some questions about the vaccine, such as how the human immune system resists the new crown virus and how to use the vaccine to safely trigger a similar immune response. By studying infected populations and animal models, it may not take long to get answers. However, some researchers said that insufficient information should not be allowed to prevent experts from launching human safety tests. Others worry that if accelerated vaccine candidates prove to be ineffective, or worse, unsafe, researchers may fall shortDevelopment and widespread application of slow effective vaccines.
To develop a coronavirus vaccine, scientists hope that the following key questions can be answered.
01 Does the body develop immunity?
Vaccines can help individuals develop an immune response to an infection without being exposed to a pathogen. According to the research results of other coronaviruses (such as four coronaviruses that cause some common colds) , most researchers speculate that SARS-CoV-2 (New crown virus) Rehabilitated patients will not re-infection within a certain period of time. However, Michael Diamond, a viral immunologist at Washington University in St. Louis, said that this speculation needs to be supported by evidence, “We don’t know much about how immune the body is to this virus.”
On March 14, a research team in China published a preprinted paper 1 , showing that two rhesus monkeys infected with SARS-CoV-2 recovered, and the virus only Caused a mild illness. Four weeks after the initial exposure of the two rhesus monkeys, the researchers exposed them to the new crown virus for the second time and found that they did not appear to be reinfected. Diamond said researchers will try to find evidence that the body can respond the same way, such as studying people who may have had multiple exposures.
02 If the body does develop immunity, how long can it last?
This is another major unknown. Coronaviruses that cause the common cold have a shorter duration of immunity; even people with high levels of antibodies to these viruses can still re-infect, said Stanley Perlman, a coronavirologist at the University of Iowa.
For SARS (Severe Acute Respiratory Syndrome) and MERS ( Middle East Respiratory Syndrome) , the correlative evidence is even more ambiguous. Perlman says his team has found that MERSAfter the patient recovered, the viral antibodies in his body were greatly reduced. He also said that his team has collected data (not yet published) , suggesting that SARS antibodies are still present in patients after 15 years of infection. However, it is unclear whether this immune response is sufficient to prevent reinfection. “ We don’t have solid evidence that immunity is persistent, and we don’t get good data from SARS and MERS. ” Perlman added.
03 What kind of immune response should vaccine developers look for?
The Phase I trial, which began last week, will test the safety of a vaccine developed by Moderna, Massachusetts. However, researchers will also closely observe the nature of the immune response elicited by the vaccine.
Moderna’s vaccine includes an RNA molecule. Like many other SARS-CoV-2 vaccines being developed, this vaccine can train the immune system to make antibodies to recognize and block the spikes that the virus uses to enter human cells. protein.
“As the first batch of vaccines, I think it is reasonable, but we may find that the antibody response that specifically targets spike proteins may not be the whole story,” Diamond said. A successful SARS-CoV-2 vaccine may require the body to produce antibodies that block other viral proteins, or make T cells that recognize and kill infected cells.
04 How do we know if a vaccine will work?
Under normal circumstances, human trials will only be conducted after the safety and effectiveness of the vaccine has been proven through animal experiments. However, Moderna’s vaccine and another vaccine developed by Inovio Pharmaceuticals are undergoing both animal testing and clinical Phase I human trials. Inovio plans to begin its first human trial in April.
“In a non-emergency situation, you may go step by step, but in the current situation, many things are moving in parallel.” said Barney Graham, deputy director of the National Institutes of Health’s Vaccine Research Center. The center is funding a vaccine trial for Moderna.
A preprint paper 2 published on March 2In the study, researchers reported that mice and guinea pigs were injected with the Inovio vaccine, a DNA molecule that carries instructions for making spike proteins. They found that the test animals produced antibodies and T cells to the virus. Kate Broderick, head of research and senior vice president of preclinical research and development, said that her team has now injected the monkeys with vaccines and will soon begin to study whether the animals can fight infection. Graham said Moderna’s vaccine is also preparing for such “challenging” studies.
He added that without such data from animals, expensive large-scale trials would not be conducted to test whether the vaccine can prevent human infections. Diamond predicts that as researchers learn more about infections from human and animal studies, they will be able to better determine which vaccines are likely to be most effective. “This may not be the most efficient vaccine development method, but it is the most convenient emergency method,” Diamond said.
05 How safe is it?
Since the vaccine is given to a large number of healthy people, and the medicine is given to people who are already sick, the safety standard for vaccines is generally higher than that of medicines. For the safety of SARS-CoV-2 vaccine, researchers mainly hope to avoid disease enhancement (disease enhancement) After the actual infection, a more severe illness appears than the unvaccinated population. According to a 2004 study of experimental SARS vaccine 3 , vaccination of ferrets after the infection of SARS virus showed destructive inflammation in the liver.
Peter Hotez, a vaccine scientist at Baylor College of Medicine in the United States, believes that candidate vaccines should be tested in animals to eliminate the possibility of disease enhancement before human trials can be conducted. He said he understands the reason for the rapid advancement of human testing of the SARS-CoV-2 vaccine, but he also said that given the potential for disease enhancement, “I’m not sure this is the vaccine you want.”
Graham said that Moderna’s vaccine is being tested, and only if human and animal studies prove the vaccine is safe will the National Institutes of Health conduct larger human studies. He said that the risk of disease enhancement is not high, but “the risk of not speeding up the development of vaccines is quite high, and only by advancing rapidly, we will be able to catch up with the next winter and have something to test practically.”
References:
1.Bao, L. et al. Preprint at BioRxiv https://doi.org/10.1101/2020.03.13.990226 (2020).
2.Smith, TRF et al. Preprint at Research Square https://doi.org/10.21203/rs.3.rs-16261/v1 (2020).
3.Weingartl, H. et al. J. Virol. 78, 12672–12676 (2004).
The original article was published under the title of Coronavirus vaccines: five key questions as trials begin on March 18, 2020 in the “Natural” News Interpretation
This article is from the WeChat public account: Nature Nature Research (ID: Nature-Research) , original author: Ewen Callaway