Editor in chief of the New England Journal of Medicine: there are many uncertainties about the new crown vaccine, but it's worth betting on
Last Update: 2020-06-19
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< br / > < br / > after < br / > two weeks, several academic institutions or companies published the results of phase 1 clinical trial of covid-19 vaccine< br / > among them, the paper of academician Chen Wei's team showed that the covid-19 vaccine developed by Chen Wei, which was based on adenovirus, produced neutralizing antibodies in human body, and no serious adverse events occurred within 28 days after vaccination< br / > in addition, an American company announced that its monoclonal antibody had achieved "exciting" results in vitro< br / > < br / > in the latest interview with the editor in chief of the New England Journal of Medicine (NEJM), Steve Morrissey, executive editor, interviewed Eric Rubin, editor in chief, and Lindsey Baden, editor in chief, about the potential problems and application prospects of convalescent plasma, monoclonal antibodies and vaccines in the treatment and prevention of covid-19< br / > < br / > they stressed that the vast majority of vaccinated people are healthy people, so "large sample study must be carried out to confirm that there is no safety problem, and then confirm the effectiveness"Moreover, the immune persistence of covid-19 vaccine is unknown and still needs to be evaluated, but "considering the seriousness of the problem and the need to shorten the schedule", it is necessary to "make a small bet" and prepare for large-scale production before determining the effectiveness of the vaccine< br / > < br / > please listen to the English interview or read the Chinese translation< br / >One company, in a news release this week, said it had developed antibodies that neutralized the virus in an infected tissue culture modelThere must be a lot of work to be done, but how should we use these antibodies? < br / > Rubin: < br / >Prevention is similar to induction of endogenous immune response to prevent infectionAlthough monoclonal antibodies are not commonly used in the treatment of infectious diseases, they have been widely used in many other diseasesThe concept of using monoclonal antibody is very similar to the concept of treatment of convalescent plasma that many people currently advocate< br / > < br / > Baden: < br / >Especially in the past 5-8 years, anti HIV mAb has been an encouraging and attractive anti-virus strategyWe can develop B cells or antibodies that can neutralize specific viruses through various molecular biotechnologyIt's like developing a drug that can attack pathogens Unlike drugs, it mimics the immune system But there is a huge gap between the effect observed in cell culture and the effect in human body We must cross this gap to know the real potential of these therapies < br / > < br / > Morrissey: < br / >? < br / > < br / > Rubin: < br / > This therapy has a long history It was born in the 19th century In 1901, the convalescent plasma therapy won the Nobel Prize < br / > < br / > however, we do not know the efficacy of convalescent plasma in covid-19 At present, there is a lack of good control trials, only a small sample of case studies Although this therapy is very attractive, and it may be useful for antibodies to block virus invasion or interfere with the important functions of the virus, the recovery phase plasma is somewhat complex < br / > although many people have recovered from the disease, it is easy to collect and use the recovered plasma, but each plasma sample is different, which means that the plasma is a non-standard product, making the interpretation of the test results more difficult The advantages of < br / > < br / > convalescent plasma are: since more than a century, plasma therapy has been used in many diseases, and people have known that it is a safe therapy, which can more easily enter the experimental stage The development of monoclonal antibody involves more safety tests We'll discuss that later < br / > The difference between Covid-19 and convalescent plasma is that we try to use it to enhance the humoral immune response to SARS-CoV-2 How is < br / > < br / > different from FFP, tetanus immunoglobulin, measles immunoglobulin, rabies immunoglobulin, VZV immunoglobulin and various immunotherapies studied in different ways for decades? Although the immunoglobulins of these pathogens are not exactly the same, they are immunoglobulins obtained in the immune response to different pathogens; however, their development philosophy is the same, that is, by collecting plasma, or trying to enhance the immune characteristics of pathogens, to obtain the immune response of rehabilitation individuals Both of these are ongoing The principle is to use one person's protective immune response, or an important factor of protective immune response, to help another person who has no time to form a protective immune response < br / > < br / > therefore, the recovery plasma is actually a mixture of different humoral immune responses, rather than a specific immune response product This complicates our interpretation of any particular study, because it is impossible to standardize the protective response of a given unit, which is the problem we want to solve in the development of monoclonal antibodies We can use drug grade compounds instead of polyclonal reactions produced by an individual < br / > < br / > Rubin: < br / > 77 < br / > we are not critical of convalescent plasma therapy Convalescent plasma is a valuable and meaningful therapy < br / > as we said, this ready-made therapy (without synthesis) can quickly enter the research stage Monoclonal antibody is a more uniform preparation, so it has its charm < br / > < br / > Baden: < br / > If it is effective, the convalescent plasma can also help us to understand the key protective factors and develop monoclonal antibodies and vaccines from a biological perspective, because it contains important elements of immune response, which can help us to find protective factors After that, on the basis of correct definition, we can model it < br / > < br / > Morrissey: < br / > < br / > how is the development of effective monoclonal antibody? < br / > < br / > Rubin: < br / > < br / > is in the development stage < br / > there are many companies interested in developing monoclonal antibodies As far as I know, there are several companies whose monoclonal antibodies are in the early stage of development < br / > which monoclonal antibodies are the best? < br / > the question remains to be answered < br / > as Lindsey said just now, although neutralizing antibodies can be tested in vitro, that is, to evaluate their effect on preventing virus infection in tissue cell culture, we still don't know what is the most critical factor to bring about the protective effect, so I think this aspect needs to be further explored < br / > in addition, the field of McAb is also full of changes Researchers can modify antibodies to have different properties, such as prolonging their half-life or changing their interactions with different immune cells It is not known how much these changes will affect the final outcome But I want to emphasize once again what Lindsey just mentioned The advantage of monoclonal antibody is that it can be mass produced Therefore, once we find one or a group of effective antibodies, it will be able to be widely used, although its price may be very expensive < br / > < br / > Baden: < br / > < br / > how to find a suitable target to neutralize or weaken the pathogenicity of the virus? < br / > if you can understand from a biological point of view which factors promote the pathogenicity or disease performance of the virus, such as virus spike protein or other important components, you can use it as a target < br / > < br / > Eric just talked about antibodies The antibody has a front end and a back end The front end is the Y part that binds to the associated antigen, which may be the spike protein The back end is the part that connects with cells and affects the half-life If we design the antibodies precisely and carry out the research systematically, these antibodies will produce the therapeutic benefits What attracts us to the McAb platform is that it can easily target different pathogens by changing the front end That is, antigen-specific antibodies can be designed for specific pathogens < br / > The McAb platform is very attractive and can be switched (by design) to target yellow fever, Ebola, Zika or other viruses If you think it makes sense, then we can transform the McAb platform < br / > < br / > Morrissey: < br / >? < br / > < br / > Rubin: < br / > In my opinion, some in vitro findings with high probability indicate the direction for future research We don't know nothing about monoclonal antibodies As Lindsey said, there are some monoclonal antibodies that have been developed to fight infection, especially HIV Therefore, we know the mechanism of action and how to maximize the ability of these antibodies to bind and clear viruses in vivo < br / > < br / > it should be pointed out that HIV antibodies are effective, but their effects are not long-term, because HIV virus will rapidly develop resistance to any antibody, including the antibody that has been studied by human body, so we have some knowledge of the characteristics of monoclonal antibodies The most important thing is that these drugs have to go through the clinical effectiveness test to confirm the efficacy, and at present, there is no known index of early mAb test to guide the mAb to pass the clinical test < br / > < br / > Baden: < br / > For example, if I am not infected, I may face virus exposure Can I prevent virus invasion through antibody? This is a bit like vaccine induced antibody, but on the contrary, we are passively receiving antibody at this time Another scenario is whether we can use antibodies to treat the disease, eliminate the virus, and prevent the disease when the virus replicates in the patient's body, whether in the early or late stage of the disease The beauty of this strategy, I think, is that it can be used for different purposes, depending on the medical needs, in which study population it has a meaningful effect, and its side effects < br / > < br / > Rubin: < br / > < br / > Please note that we do routinely use antibodies as protective measures against other infectious diseases For example, an individual who has been exposed to rabies or a susceptible population of varicella zoster virus may receive immunoglobulin injection But these drugs are not monoclonal antibodies, they are
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