COVID-19: Antibody and vaccine development after strain mutation
COVID-19: Antibody and vaccine development after strain mutation. How to deal with antibody and vaccine development after strain mutation?
The COVID-19 epidemic is raging around the world. More than 60 million people have been infected, and more than one million people have lost their lives because of the COVID-19 virus. Our response to the new coronavirus is mostly to wear masks and physical isolation to reduce the chance of infection; most patients receive symptomatic adjuvant treatment, and no other more effective treatment options are available.
The development history of human civilization is also a history of mutual compromise and peaceful coexistence with bacteria and viruses. In the process of getting along with viruses and bacteria, human beings have encountered the danger of almost extinction several times. However, relying on their own wisdom, humans finally learned to compromise with viruses and bacteria, and humans have reproduced today.
Back then, the smallpox virus ravaged the world, and an accidental discovery changed the fate of Europeans. Scientists from various countries have developed a series of vaccines to control variola virus based on the vaccinia virus. The smallpox virus has since disappeared. People are looking forward to a miracle once again, to develop new vaccines or antibodies to control the spread of the new coronavirus or treat it .
So far, scientists from various countries to develop a vaccine or antibody is still in clinical trials, and there have been a secondary infection and the emergence of new variants, new prevention and treatment of diseases of the crown, there are still a lot of uncertainty!
Summary of recent new coronavirus information
01 More and more people are infected with the new coronavirus again
The top international scientific journal Science Magazine published a report titled: More people are getting COVID-19 twice, suggesting immunity wanes quickly in some. The report stated: More and more people are getting COVID-19 twice, suggesting immunity wanes quickly in some. The immunity of some people is rapidly declining.
On April 17 this year, 22-year-old Sanne de Jong tested positive for the COVID-19 and developed mild symptoms for 2 weeks. On May 2, the COVID-19 test turned negative. However, in late June this year, Sanne de Jong again showed symptoms of new coronavirus infection and was diagnosed.
The emergence of secondary infections indicates that the immune system is weak against the COVID-19. This not only affects the risks faced by patients who have recovered, but also raises questions about whether vaccines can provide enough protection for the human body.
02 People who are not infected with COVID-19s can detect COVID-19 antibodies
Researchers from the Francis Crick Institute and University College London published a research paper on Science titled: Preexisting and de novo humoral immunity to SARS-CoV-2 in humans.
This study found that some people who are not infected with COVID-19 also have antibodies that can target and target the new coronavirus (SARS-CoV-2). Further research has shown that these antibodies are the immune system in the infection of the coronavirus that causes the common cold. It is produced when the virus is a virus and can provide a certain degree of protection against SARS-CoV-2.
In fact, these seasonal coronavirus infections occur frequently and often cause a mild, common cold-like illness. These four coronaviruses that infect humans and cause mild symptoms are: 229E (α-CoV), NL63 (α-CoV), OC43 (β-CoV) and HKU1 (β-CoV). In addition, three other coronaviruses that are known to infect humans and cause more serious infections are: MERS-CoV, SARS-CoV and SARS-CoV-2.
Human coronavirus 229E, NL63, OC43 and HKU1 are commonly infected all over the world. Considering that they are closely related to the new coronavirus, there may be an immune cross-reaction between the two, thus providing some protection against SARS-CoV-2.
03 Variant strains of new coronavirus appear in mink
“Science” Working Paper reports (working paper), the researchers of the viral genome mink farms suffered COVID-19 viral infection into the sequence analysis, found COVID-19 virus mutated in mink, resulting S protein in a few amino acids Change, and is likely to be insensitive to the current COVID-19 vaccine .
There are mainly four mutations: Y435F, 69-70deltaHV, I692V and S1147L . Wherein the most common mutations Y435F, mutation of tyrosine 453 to phenylalanine, an S protein with the host receptor ACE2 binding region conservative amino acid substitutions, researchers believe is an adaptive mutation Y435F mink against ACE2, which The increased affinity for human ACE2 may explain why the mutant strain re-entered the human world.
04 N439K mutant weakens neutralizing antibody activity
The new coronavirus D614G mutant strain can promote the virus to have higher infectivity, but the previous neutralizing antibodies are still effective.
However, the study “The circulating SARS-CoV-2 spike variant N439K maintains fitness while evading antibody-mediated immunity” published on bioRxiv on November 5 showed that the N439K mutant strain affected the receptor binding domain (RBD) of the S protein. , Has developed a certain tolerance to neutralizing antibodies, which poses a challenge for the subsequent comprehensive use of antibodies and vaccines.
Phenomenon problem expansion
People who are not infected with SARS-COV-2 also have antibodies that can target and target the new coronavirus. Problems such as the easy mutation of the new coronavirus and the “resistance” of the mutant strain to the neutralizing antibody have brought our clinical diagnosis and treatment. new challenge. Is rapid serological diagnosis feasible? How is the differential diagnosis of nucleic acid diagnosis? How should vaccine and antibody research and development institutions respond?
a. Nucleic acid testing is still the gold standard
There are many false positive problems in serological testing, and nucleic acid testing is still the gold standard for the diagnosis of new coronavirus. In order to prevent the false negative problem of nucleic acid diagnosis, according to the requirements of ” Technical Review Points for Registration of New Coronavirus Nucleic Acid Detection Reagents ” issued by the Medical Device Technical Evaluation Center of the State Drug Administration on February 12, 2020 , nucleic acid diagnosis requires positive control materials and negative control materials .
Positive quality control products can be represented by 1 to 2 virus strains, and should contain natural or artificially synthesized target sequences (such as pseudoviruses) that can be detected by the kit.
Negative control products mainly involve the verification of cross-reaction. Suggestions include coronavirus (HKU1, OC43, NL63, 229E), SARS coronavirus (pseudovirus can be used), MERS coronavirus (pseudovirus can be used), influenza Virus, parainfluenza virus, respiratory syncytial virus, adenovirus, etc.
b. Antibody development needs to consider variation
Earlier, when the State Council’s Joint Prevention and Control Mechanism held a press conference to introduce the COVID-19 vaccine, Tian Baoguo, deputy director of the Department of Social Development and Technology of the Ministry of Science and Technology, said that “the COVID-19 virus has mutations, but the mutations are not large. Even if individual sites of the S protein are mutated, The structure of the protein itself has little impact, and therefore has little impact on its immunogenicity, and does not affect the development of anti-and vaccines. For some “extraordinary” mutations, we must timely study and judge to provide timely warning and science for the vaccine development team Reference .
So, how do we respond to some of the mutant strains that have emerged or will appear in the future that may be “resistant” to our antibodies or vaccines? How do antibody companies timely evaluate the effectiveness of their antibodies or vaccines? It can be seen from the existing research reports that the use of fake viruses for evaluation is an effective method.
The existing pseudovirus construction vectors include the lentivirus system and the VSV virus system, which use the Spike protein of the new coronavirus to replace the coat spike protein of the original virus. The construction of mutant strains can realize mutations at the amino acid level by mutation of Spike’s nucleotide sequence, and quickly obtain SARS-COV-2 mutant pseudoviruses for evaluation of antibody neutralization effects.