AIDS teams new crown research: a rare antibody appears repeatedly to prompt vaccine clues

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 AIDS teams new crown research: a rare antibody appears repeatedly to prompt vaccine clues


As a leading scholar in the field of AIDS, nussenzweigs research focuses on the molecular mechanism of innate and adaptive response of the immune system, combining biochemistry, molecular biology and genetics. He focuses on B-lymphocytes and HIV-1 antibodies. In response to the outbreak of covid-19, nussenzweig has extended its research to sars-cov-2, and has isolated and identified highly effective neutralizing antibodies from recovered patients.

Another corresponding author, Professor Paul bieniasz, is also a leading scholar in the field of AIDS. His research attempts to define how host genes affect viral replication, with a focus on human and primate immunodeficiency viruses. Its laboratory is dedicated to characterizing the host functions of virus imitation, manipulation and other ways of utilization, as well as the evolution characteristics of defense cells against virus infection.

On May 13 local time, Mike Ryan, whos head of health emergency program, said that the new coronavirus could become a long-term problem, its difficult to predict when it can be defeated, and it could become an epidemic virus that will never disappear. Ryan, taking AIDS as an example, pointed out that although HIV has not disappeared, human beings have found treatment and prevention methods, and people no longer fear AIDS as before.

Appendix: research methods

However, little is known about the human antibody response to sars-cov-2. In this study, the team reported 68 convalescent covid-19 patients, none of whom were hospitalized. The distribution of the semimaximum neutralization titer range of the plasma collected by these rehabilitation patients at 30 days after symptom onset was different, ranging from undetectable (18% of the samples) to less than 1:1000 (78% of the samples), and only 3% of the rehabilitation patients were more than 1:5000.

The antibody clone shows the amplification and cloning of RBD specific memory B cells (which express closely related antibodies) in different individuals. Although the plasma titer is low, the semi inhibitory concentration of antibodies against unique epitopes on RBD can be neutralized as low as ng / ml. As a result, most individuals recovering from covid-19 who were not hospitalized did not have a high level of neutralization activity in their restorative plasma. However, rare but recurrent RBD specific antibodies with effective antiviral activity have been found in all tested individuals, indicating that vaccines based on these antibodies may be generally effective.

At the time of collection, the 68 people had no symptoms for at least 14 days. Only one sars-cov-2 nucleic acid test positive asymptomatic, the other 67 participants average onset time is about 30 days (17-48 days) before sample collection. In this cohort, symptoms lasted an average of 10 days (0-28 days) and were not admitted. The most common symptoms were fever (82.4%), cough (64.7%), myalgia (55.9%) and fatigue (54.4%), and complications were rare (8.8%). There was no significant difference between genders, patients and contacts, duration or severity of symptoms, or time from symptom onset to sample collection.

88% and 66% of the plasma samples tested showed RBD specific IgG and IgM antibodies (at least 2 standard deviations higher than the control group). However, only 40% and 21% of the plasma samples showed IgG and IgM antibody responses to the anti trimer s protein (higher than at least two standard deviations in the control group). There was no significant difference between the IgG and IgM antibody levels and the sampling time, age, gender, case or contact person. On the contrary, the binding of IgG antibody to RBD and S protein is directly related to the duration of symptoms, but the binding of IgM antibody to RBD and S protein is not related to the duration of symptoms. Finally, there was no significant difference in antibody level to S protein between sexes, but the effect of IgG binding antibody to RBD in women was lower than that in men.

To measure the neutralization activity of recovered plasma, the researchers used a pseudovirus assay, which uses HIV-1-based virus particles carrying nano luciferase reporter gene and sars-cov-2s protein. The overall level of neutralization activity in the cohort measured by half maximum neutralization titer (NT50) was generally low, 18% of which could not be detected, and 78% of which were below 1000. The geometric mean of NT50 is 212 (arithmetic mean = 850), and only 2 people have NT50 of more than 5000. It was found that neutralization activity was related to the duration and severity of symptoms, but not to the time of sample collection related to symptoms, age, gender or the onset of case / contact status. It is worth noting that the level of IgG antibody binding RBD and S is closely related to NT50.

In order to determine the nature of antibodies induced by sars-cov-2 infection, B lymphocytes with RBD binding receptors were isolated from the blood of six participants, including two patients with the best antibody neutralization activity. The frequency of antigen-specific B cells was determined by their ability to bind phycoerythrin (PE) and bv711 labeled RBD. The range of circulating B cells in convalescent covid-19 was 0.07 to 0.005%, but it could not be detected in the control group. The researchers obtained 534 pairs of IgG heavy and light chain (IgH and IGL) sequences from single RBD binding B cells of six recovery individuals by reverse transcription and PCR. Compared with the human antibody library, there are several igh and IGL genes that exceed the standard. The average number of nucleotide mutations in the V gene of IgH and IGL was 4.2 and 2.8, respectively, which was lower than that of antibodies cloned from individuals with chronic infection, such as hepatitis B or HIV-1, and similar to those derived from circulating IgG memory cells with primary malaria infection or non antigen enrichment.

In order to examine the binding characteristics of anti sars-cov-2 antibodies, the researchers expressed 34 representative antibodies, 24 of which were from clones and 10 from monomers (found in the plasma of 3 participants). ELISA analysis showed that 94% (32 of 34 antibodies) combined with sars-cov-2rbd at a half maximum effective concentration (EC50) of 6.6ng/ml,. To determine whether these antibodies have neutralizing activity, the researchers tested the SARS cov2 strunc pseudovirus. Among the 32 RBD binding antibodies tested, 20 were found to have small neutralization in the range of 4.4 to 709 ng / ml at the semi maximum inhibitory concentration (IC50) of the order of nanogram / ml. An effective neutralizing antibody was found in individuals, independent of plasma NT50. For example, C002 and C121 were obtained from cov21 and cov107 individuals with plasma NT50 values of 5053 and 298, respectively, and IC50 was 8.9 and 6.7ng/ml, respectively. Finally, the cloning of antibodies sharing IGHV and iglv genes is one of the best neutralizers. For example, antibody C002 with ighv3-30 / igkv1-39 has the best plasma neutralization activity. The researchers concluded that even people with moderate plasma neutralization activity had rare IgG memory B cells that produced effective neutralizing antibodies to sars-cov-2.

In order to determine whether the human anti sars-cov-2 monoclonal antibody with neutralizing activity can bind to different domains of RBD, the researchers carried out double-layer interference measurement experiments, in which the pre formed antibody RBD immune complex was exposed to the second monoclonal antibody. The antibodies tested included two groups, while C002 and c105 combined with the pre formed c121-rbd complex, while C104, C110 and c119 did not. The conclusion is that, like SARS CoV, there are at least two different neutralization epitopes in RBD of SARS cov-2.

Through single cell antibody cloning, human monoclonal antibodies with neutralizing activity against pathogens such as viruses and parasites were obtained in natural infection. In model biology and early clinical research, several effective protection and treatment methods have been shown, but only one antiviral monoclonal drug is currently in clinical use. Compared with small molecule drugs, antibodies are relatively expensive and more difficult to produce. However, they are different from drugs in that they can participate in the host immune system through a constant domain of FC u03b3 receptor binding to the host immune cells. These interactions can enhance immunity and help clear pathogens or infected cells, but they can also lead to increased dengue and coronavirus infections. This problem hinders the development of dengue vaccine, but it will not interfere with the clinical application of effective neutralizing antibody. It can be modified to prevent FC u03b3 receptor interaction and maintain the protection of viral pathogens.

Antibody is an essential element of most vaccines, and may become a key component of an effective vaccine against sars-cov-2. The observation shows that the plasma neutralization activity of most patients in recovery period is low, but in patients with abnormal plasma neutralization activity, it can be found that anti sars-cov-2rbd recurrence antibody with effective neutralization activity, which shows that human beings have the inherent ability to produce anti RBD antibody which can effectively neutralize sars-cov-2. Therefore, the vaccine that can specifically and effectively induce antibodies targeting sars-cov-2rbd may be particularly effective.

Demographic and clinical characteristics of participants:

(function(){( window.slotbydup=window .slotbydup||[]).push({id:u5811557,container:ssp_ 5811557, async:true Zhang Wenhong, the latest novel coronavirus pneumonia vaccine is expected to be the fastest in 2021 3 to 6 months. The source of this article is: surging news editor: Zhang Tianqi NBJ10752