Although the association between poor nutrition and illness has long been recognized, there is a lack of reliable, objective, short-term screening methods to evaluate nutritional risk. Determination of the prealbumin level is a cost-effective and objective method of assessing severity of illness in patients who are critically ill or have a chronic disease.

A prealbumin test may be used to:

* Find out if you are getting enough nutrients, especially protein, in your diet

* Help diagnose certain infections and chronic diseases

Low prealbumin scores mean that you are likely to need a nutritional assessment. Low prealbumin scores may also be a sign of liver disease, inflammation, or tissue death (tissue necrosis). High prealbumin scores may be a sign of long-term (chronic) kidney disease, steroid use, or alcoholism.

TABLE 1 Prealbumin Risk Stratification

Source:  Prealbumin in Nutritional Care Consensus Group. Nutrition 1995;11:170.

Test results may vary depending on your age, gender, health history, the method used for the test, and other things. Your test results may not mean you have a problem. Ask your healthcare provider what your test results mean for you.

Creative Diagnostics can support your testing by providing native prealbumin antigens and several monoclonal antibodies. Our new high-affinity mouse monoclonal antibodies have been validated both in ELISA and Immunoturbidimetric. Clones can be paired with each other and are suitable for the development of diagnostics assays.

Featured Prealbumin/TTR Antigens and Antibodies

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But is Vallance right? Once we have antibodies, are we protected?

Strictly speaking, not everyone who has not been infected with COVID-19 is immune to this disease. Our body does have the ability to protect itself. In addition, our immune system can learn and remove viruses during infection. This is basically the main method of treatment at present. The hospital supports COVID-19 patients while their own bodies are fighting the virus. Unfortunately, for too many people, the virus won this battle, and they left.

The immune system has several layers. The first and top layers consist of mechanical barriers, such as hair in the nose and mucus on the airways, which prevent pathogens (such as SARS-CoV-2) from entering the lung cells. Further down, these lung cells are filled with intrinsic defenses to prevent infection. But most viruses have evolved to bypass these defense systems and quickly defeat these defenses. This attack triggered the next wave of “innate” immunity. This includes a fast, broad-spectrum defense system, including direct antiviral killing mechanisms or promoting inflammation, thereby kicking the virus out of the body.

For most people, this natural response slows and controls the infection, making the last immune layer, adaptive immune system, work. Adaptive immunity consists of antibodies produced by B cells and antiviral killer cells, T cells. Both B and T cells can learn how to respond to specific threats during infection. This reaction usually takes a while to work, but it can remain for many years, forming a memory of past infections, such as MMR injections to prevent measles, mumps and rubella.

It is clear from the research conducted on SARS-CoV-2 that those infected with the SARS-CoV-2 virus will develop the above-mentioned multilayer immune response. In most cases, in the laboratory, antibodies produced during SARS-CoV-2 infection will bind, recognize, and prevent infection. However, there is not much information about the activity of T cells.

As more and more people infected this virus and survived by producing antibodies and T cells to fight against SARS-CoV-2, we may eventually reach a threshold of “herd immunity”. This does not mean that everyone has immunity, but because most people have immunity, those susceptible people who do not have immunity are less likely to contract the disease.

The problem of achieving herd immunity through natural infection is that a large number of vulnerable people, such as those with weakened immune systems, pregnant women or the elderly, are likely to get sick and die. This is why obtaining high levels of vaccine-mediated immunity is essential to protect them. Ideally, we need a safe and effective vaccine to help us get immunized.

That is to say, as the pandemic develops, herd immunity may start to play a role later and help control infection in the short term. But this should not be the only target controlled by SARS-CoV-2. On the contrary, as outlined by the World Health Organization, active detection and isolation measures are the best way to slow the spread of this pandemic.

Since some detection methods have been developed so far, identifying people with SARS-CoV-2 antibodies (infected and recovered) will undoubtedly help determine the spread of a pandemic. But there are still many problems unsolved, for example, we don’t know how long the immunity will last, and we don’t even know how many antibodies are needed to be classified as protected. A safe and effective vaccine will greatly eliminate this doubt, and should continue to maintain the key goal of combating COVID-19.

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Glycosylation is a widespread protein post-translational modification that is complex and variable in structure and plays an important role in cells and organisms. More than 50% of the proteins in the organism are glycosylated, including nucleoporin, chromatin protein, RNA polymerase II, protein translation regulators, transcription factors, etc. Their changes are involved in various life activities, such as cell recognition, cell differentiation, cell development, signal transduction and immune response. They are also related to occurrence and development of various diseases, such as tumors, neurodegenerative diseases, cardiovascular diseases, metabolic diseases, immune diseases and infectious diseases. Similarly, virus replication and invasion of the host are closely related to the glycosylation modification of its own structural proteins.

Comparing with the glycosylation of the envelopes of several common viruses, there are 8 to 15 glycosylation sites for Ebola virus, 5 to 11 for IAV (influenza virus), and 4 to 11 for HCV (hepatitis C virus), and 20 to 30 for HIV (AIDS virus). It has been found that the glycosylation site of SARS-CoV-2 is at least twice that of HIV.

The figure below shows the predicted glycosylation sites on the viral protein shell with green the SARS-CoV-2 glycosylation site, and blue the SARS-CoV glycosylation site. Highly glycosylated sites phenomenon can be observed.

Fig 1. Predicted Glycan shield (spheres) of SARS-CoV-2 and SARS-CoV Spike Glycoproteins.

Source: DOI: 10.1080 / 22221751.2020.1739565

Professor Raymond Dwek, the founding director of the Oxford Glycobiology Institute at Oxford University, joined the online international discussion at the invitation of the World Association of Scientists (WLA). He said that this highly glycosylated sites phenomenon is bringing great difficulty to vaccine research and development. Scientists represented by Professor Dwek first discovered the glycosylation phenomenon in the virus protein shell. The new study found that SARS-CoV-2, as a highly glycosylated spherical particle, has at least 66 glycosylation sites and is more prone to mutation. This virus has many similarities with SARS-CoV in 2003. Studies have shown that of the 69 glycosylation sites of SARS-CoV, 54 are similar or identical to SARS-CoV-2.

“In a simple analogy, glycosylation sites are like camouflage props.” The vaccine is actually a “hollowed out” harmless virus so that the body’s immune system can recognize it and form antibodies endogenously. Professor Dwek said that the vaccine should evoke an immune response to attack the virus, but when the virus really invades the body, these highly camouflaged external sites can deceive the immune system’s detection and help the virus survive.

For such a global public health issue, researchers have been searching for solutions with great effort. Recently, many articles about S protein glycosylation sites and sugar chain types of the novel coronavirus have been published in various platforms and journals such as bioRxiv, Science, Cell, etc. These research papers have aroused widespread concern in the field of basic scientific research and the pharmaceutical industry.

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The first stage: virus invasion

The first stage of coronavirus infection is Spike(S) protein-mediated attachment to the cell surface via S protein to the ceramide acid portion (acidic carbohydrate with 9 carbon atoms) or heparan sulfate. This infection strategy is very effective because there are many types of receptor molecules on the surface of all mammalian cells, thus creating abundant conditions for plasma membrane attachment. After binding, the virus particles actively rearrange the cytoskeleton by regulating the FAK/Cofilin/Rac/Cdc42 pathway.

The second stage: transport

In the second phase, some studies revealed that actin and tubulin are complementary cytoskeletal components of intracellular transport. Researchers explored the function of F-Actin in intracellular localization. Jasplakinolide (a cell-permeable F-actin stabilizing compound) inhibits the plasma membrane binding of virus particles during virus invasion, while cytochalsin D (a F-actin depolymerization compound) does not inhibit the invasion of the virus, but disrupts the normal positioning of the virion from the surrounding nucleus to the cytoplasmic region. The C-terminal peptide (S protein) of the coronavirus spike protein binds to several β-tubulin subtypes in a coronavirus-specific manner, and the chaotic peptides show that the binding is not due to random ionic charge interactions. Therefore, the transport of virions within cells utilizes a variety of cytoskeletal structural proteins to navigate and locate specific areas within the cell.

The third stage: assembly and maturity

After the virions are transported to the perinuclear area, the coronavirus RNA leaks from the vesicles and virions, and enters the nucleus for reverse transcription and replication. The DNA replicon is then transcribed as RNA and enters the Golgi/ER/microtubule organization center from the nucleus. Initially, the nucleocapsid (N) protein binds to the RNA copy and to the vesicle membrane, and then the N and E proteins mature further, which is required for the assembly of basic virus-like particles (VLPs). If the S protein is co-expressed, it will be incorporated into the virus particles. Under the synergistic effect of a variety of cytoskeleton and membrane regulatory proteins (such as HDAC6, ubiquitin and Rab GTPases), the assembly is assisted by concentrating packaging components.

The fourth stage: release

The genetic fusion of the SARS nucleocapsid or SARS S protein with GFP makes it possible to track non-infectious virus particles by fluorescence microscopy. Scientists used this technique to monitor the release of SARS-CoV and found vesicles fused into a multi-particle mass. This transport is sensitive to Brefeldin A, indicating that the secretory pathway is being used. Other studies have found that nocodazole can effectively inhibit the transport of virions to the plasma membrane, indicating that microtubules are an important part of the virus’s export outlet. Rab11 involves KHC binding for microtubule transport and then binding to myosin to help traverse the periocular actin matrix and release from the cells.

In general, there are many ways for coronavirus to enter the cell through the attachment and invagination of the plasma membrane. Subsequently, actin, tubulin, dynein and myosin cytoskeletal components need to be transported to the correct location for replication. After reverse transcription and transcription, the positive-strand RNA is packaged on the scaffold of the Golgi/ER/microtubule complex. Virus particles wrapped in vesicles move along the microtubules, then fuse with the plasma membrane and escape from the cells.

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Clinical data indicate that after the initial stage of viral infection, approximately 30% of COVID-19 patients will develop severe disease with progressive lung injury. Further research found that part of the reason was caused by excessive inflammation. Through clinical studies, it was found that pulmonary complications are caused by the destruction of the vascular barrier. Damage to the vascular barrier can lead to tissue edema, endothelitis, activation of the coagulation pathway and the development of disseminated intravascular coagulation (DIC) and uncontrolled inflammatory cell infiltration.

Under normal physiological steady-state conditions, blood vessels are usually surrounded by vascular endothelial cells to maintain the integrity of blood vessels. Vascular endothelial cells control inflammation by restricting the interaction of EC immune cells and EC platelets, inhibit coagulation by expressing coagulation inhibitors and blood clot lytic enzymes, and can produce glycogenase with anticoagulant properties. In addition, recent studies have found that a subtype of pulmonary capillary ECs has a similar profile to gene expression related to antigen presentation mediated by MHC class II. Compared with ECs of other organs, the characteristics of immunomodulation of lung ECs are more obvious. These all imply that pulmonary ECs seem to be related to coagulation and excessive inflammation in ARDS.

A recent clinical study on SARS-CoV-2 found that vascular leakage and pulmonary edema in severe COVID-19 patients are caused by multiple mechanisms. First, SARS-CoV-2 can directly infect the EC of multiple organs of patients. These infected ECs exhibit extensive endothelitis characterized by EC dysfunction, dissolution and death. Second, it is well known that SARS-CoV-2 binds to the ACE2 receptor, which can impair the activity of ACE2. It is worth noting that decreased ACE2 activity will indirectly activate the kallikrein-bradykinin pathway, thereby increasing vascular permeability. Third, activated neutrophils recruited to the lung EC produce tissue toxic mediators such as reactive oxygen species (ROS). Fourth, stimulation of immune cells, inflammatory cytokines and vasoactive molecules will increase EC contractility, which in turn leads to loosening of the connections between endothelium. This will cause the EC to separate, resulting in an endothelial space. Finally, the cytokines IL-1β and TNF activate glucuronidase and degrade glycocalyx, but also upregulate the expression of hyaluronan synthase, resulting in increased deposition of hyaluronic acid in the extracellular matrix and promoting Liquid retention. These mechanisms together lead to increased vascular permeability and vascular leakage.

In addition to vascular leakage, activation of the coagulation pathway is also an established feature of patients with severe COVID-19, and may further develop into disseminated intravascular coagulation. The study found that this is also related to EC activation and dysfunction. Because of the destruction of vascular integrity and the death of EC, the basement membrane of thrombosis is exposed, which in turn leads to the activation of the coagulation cascade. In addition, ECs activated by IL-1β and TNF initiate coagulation by expressing P-selectin, von Willebrand factor and fibrinogen binding to platelets. In turn, ECs release trophic cytokines, further increasing platelet production. In addition, platelets also release VEGF, which triggers ECs to up-regulate the expression of tissue factor, which is the main activating factor in the coagulation cascade. In response, the body will take appropriate measures to dissolve fibrin-rich blood clots, which explains why high levels of fibrin breakdown products can indicate a poor prognosis. Due to disseminated intravascular coagulation and blockage/congestion caused by inflammatory cells to small capillaries, and possible thrombosis in large blood vessels, lung tissue ischemic, triggering angiogenin and potential EC hyperplasia. The latter can aggravate ischemia, and angiogenesis can be used as a rescue mechanism to minimize ischemia. However, the newly formed blood vessels can also serve as channels for inflammatory cells and are attracted by activated ECs, thereby promoting inflammation.

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1. Protease inhibitor

The anti-viral drug Lopinavir/Ritonavir developed for HIV can effectively inhibit the important role of proteases in the replication and function of the virus, thereby interfering with the assembly process of the virus to make it non-infectious and ultimately prevent virus infection. Low-dose ritonavir can inhibit the liver’s catabolism of lopinavir, and achieve the effect of improving the bioavailability of lopinavir. Therefore, the combined use of two protease inhibitors can effectively improve the antiviral treatment effect. The protease activity of HIV is similar to that of SARS-CoV-2, but the target structure is different. Therefore, whether this drug is really effective against the SARS-CoV-2 still needs to pass rigorous clinical verification and must be used with caution.

2. RNA-dependent RNA polymerase (RdRP) inhibitor

Remdesivir (GS-5734) is a nucleoside analog developed by Gilead, a broad-spectrum antiviral drug. The drug was used in clinical trials against Ebola virus infection, but the results were not satisfactory. Remdesivir acts on RdRP and achieves antiviral effects by inhibiting viral RNA replication. Previous studies have confirmed that Remdesivir has certain effectiveness against SARS and MERS. Based on the similarity of the catalytic site structure of the SARS-CoV-2 and that of the SARS and MERS, it can be speculated that the target of the drug against the SARS-CoV-2 may be also equally effective.

Another kind of RdRP inhibitor, Favipiravir, is a class of broad-spectrum antiviral drugs that has been marketed and has a good therapeutic effect on severe influenza and drug-resistant patients, and can also effectively prevent the replication of the virus in the host cell. It is currently under clinical research for the SARS-CoV-2.

3. Antiviral drugs targeting the host

In addition to the above two drugs, there is a class of small molecule drugs that can regulate the interaction between the SARS-CoV-2 and the host by targeting the host and effectively inhibit the virus from invading human cells, which may also have certain therapeutic potential. These include chloroquine, an antimalarial drug that has been used clinically for more than 70 years, hydroxychloroquine, used in the treatment of autoimmune diseases, and Abidor developed for influenza viruses. These drugs are aimed at the targets of viruses invading human cells and cell fusion.

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Chemical small-molecule drugs: Small-molecule drugs are currently one of the types of drugs that are expected to be used for the treatment of SARS-CoV-2. There are now multiple small-molecule drugs in clinical trials, and their effectiveness and safety against the coronavirus needs to be further verified.

Biomacromolecule drugs: These drugs have high specificity and strong continuity and compliance in the body, but their production cost is high, and because they only act on the cell membrane and outside the membrane and cannot enter the cell, so the target is limited. At present, no specific antibodies have been found to conduct clinical trials in the research of the coronavirus. At the same time, by extracting neutralizing antibodies from the plasma of some recovered covid-19 patients with sufficient concentration of effective antibodies, the potentially harmful components can be removed to treat critically ill patients, but it is unlikely to be promoted on a large scale.

Gene therapy: A disease treatment method developed in recent years. It usually uses transgenic methods to make up for missing functional genes or strengthen gene functions. A variety of methods have been developed, such as precise gene editing. However, there is no gene therapy for the coronavirus. This method is generally for chronic, long-term viral infections, such as gene editing of human cells, so that the pathogens lose the ability to infect the cells, or suppress the virus gene expression through RNA interference.

Cell therapy: Also a disease treatment method developed in recent years. One of the cell treatment methods is to supplement and replace the missing cells, such as the use of stem cells; one is to regulate the body’s immunity by cytokines secreted by the transplanted cells, and this way is not to supplement or replace the cells, and then the transplanted cells will disappear; the other is that the transplanted cells can target and attack specific harmful cells, such as the specific recognition and removal of cancer cells by CAR-T cells. Cell therapy has been studied in the treatment of the SARS-CoV-2, such as the use of mesenchymal stem cells for immune regulation. In the future, we can also consider using specific stem cells for tissue repair and regeneration; organoids derived from stem cells can be used for disease modeling and drug screening.

Medical device treatment: In addition to drug treatment, respiratory support treatments that rely on medical devices, such as oxygen therapy, invasive mechanical  ventilation, extracorporeal membrane oxygenation (ECMO), and circulation support, also played an important role in the treatment of severe and critically ill patients with COVID-19.

Traditional Chinese medicine treatment: SARS-CoV-2 belongs to the category of “epidemic” diseases of traditional Chinese medicine. Its research idea is different from Western medicine. It does not aim at a specific target but cures the disease in a systematic way. Through in-depth observation and treatment of patients, on the basis of summarizing and analyzing the diagnosis and treatment schemes of traditional Chinese medicine across the country, combing and screening the treatment experience and effective prescriptions in various regions, it is necessary to judge its effectiveness and safety through rigorous clinical trials.

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Cell Survival

From the previous introduction, we can know that UPR can promote cell survival, thereby reducing ER stress and restoring homeostasis. However, long-term UPR activation induces apoptosis via the PERK–eIF2α–ATF4–CHOP pathway. Studies have shown that the CHOP encoded by the gene DDIT3 can induce the expression of pro-apoptotic genes (such as DR5, TRB3, BIM and PUMA), and inhibit the expression of BCL2, thereby triggering apoptosis when the ER stress is triggered. In addition, ATF4-CHOP heterodimer also initiates the restoration of mRNA translation, resulting in increased protein synthesis, ATP depletion, oxidative stress and cell death. If the Ddit3 gene is deleted from the cell, ER stress causes less protein aggregation in the endoplasmic reticulum and reduces oxidative stress and apoptosis. If any other UPR gene is deleted, this will not happen instead. In addition, CHOP also activates ER oxidase 1α (ERO1α), an oxidoreductase that mediates the transfer of electrons to molecular oxygen during the formation of disulfide bonds to produce hydrogen peroxide. This reaction increases the ability to generate reactive oxygen species (ROS) from the ER and inositol-1,4,5-triphosphate receptor (IP3R) -mediated Ca^{2 +} efflux. Ca^{2 +} released from ER is absorbed by mitochondria through the ER membrane associated with mitochondria, thereby promoting mitochondrial ROS production through different mechanisms. The flux of Ca^{2 +} between the endoplasmic reticulum and mitochondria may combine the protein folding ATP requirement with the mitochondrial production of ATP. Therefore, endoplasmic reticulum stress causes oxidative stress and impairs mitochondrial function, resulting in cell death in a CHOP-dependent manner.

Cell Growth And Differentiation
Cells need a large amount of protein in the process of proliferation and differentiation, which will cause an increase in protein synthesis, which is the main cause of endoplasmic reticulum stress and UPR activation. During ER stress, the monitoring mechanism delays the process of ER and cell division. It depends on the mitogen-activated protein kinase (MAPK) SLT2, but not on PERK, IRE1α and ATF6α (UPR sensors).
The discovery of the role of UPR in cell differentiation is demonstrated by the need for the IRE1α–XBP1 pathway in plasma cell differentiation. Since cell differentiation is related to the six-fold expansion of ER, the IRE1α–XBP1 pathway is required for the expansion of the secretory pathway in cells with large amounts of protein secretion. Interestingly,  the increase of immunoglobulins load is not reason of the activation of the IRE1α–XBP1 pathway . Instead, it is caused by a differentiation-dependent signal from the B cell receptor that upregulates genes encoding components such as secretory pathways and plasma cell transcription factors, such as Mist1. Surprisingly, deleting PERK, eIF2α-P or ATF6α did not cause defects in plasma cell differentiation. In addition, XBP1 can induce a wide range of secretory pathway genes, as well as increased endoplasmic reticulum and lysosomal protein content, mitochondrial quality and function, ribosome number, and protein synthesis levels. Therefore, the IRE1α–XBP1 pathway significantly promotes the characteristic phenotypes of specialized secretory cells, such as gastric zymogen cells, β cells, and intestinal Paneth cells.

Cellular Metabolism

When the researchers discovered that PERK deletion and the mutation of the PERK phosphorylation site of eIF2α could cause defects in glucose metabolism, the link between ER stress signals and metabolism was confirmed. ER homeostasis and UPR activation are key to glucose and lipid metabolism. The steady state of blood glucose is strictly controlled by the levels of insulin and glucagon in the blood. ER homeostasis and UPR activation in insulin-secreting beta cells and hepatocytes that respond to insulin and glucagon play an important role in maintaining glucose homeostasis. And related studies have found that each UPR sub-pathway seems to maintain a liposomal homeostasis through different mechanisms.

Protein Secretion
ER is responsible for post-translational modification, folding and transportation of secreted proteins (such as cytokines and hormones). Endoplasmic reticulum stress inhibits the synthesis and secretion of secreted proteins through various mechanisms. A well-studied example is insulin. In beta cells, proinsulin interacts with many ER proteins to promote their folding and transport. For example, embryo knockout of XBP1 significantly impaired proinsulin processing. Because increased ER pressure and excessive activation of IRE1α induced RIDD, which degrades mRNAs20 encoding proinsulin processing enzymes. Therefore, during the transcription, translation, and secretion stages, endoplasmic reticulum stress and UPR activation affect insulin levels. Similarly, endoplasmic reticulum stress and the UPR pathway also affect other secreted proteins at the level of transcription or translation. Because these secreted proteins affect the function of distant organs, endoplasmic reticulum stress not only damages the survival and function of secreted cells, but also affects the entire organism.

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Hybridoma technology

Hybridoma technology originated in the mid-1970s and is easy to understand. Choosing the right technique depends on the use of the antibody you need. If you need high-yield antibodies, hybridoma technology is the right choice. But its problems are long cycles and incomplete recognition of epitopes.

Phage display

Phage display technology is to insert the antibody genes isolated from innate and acquired individuals into phage DNA. An antibody molecule includes a variable region of an antibody that binds to an antigen, called scFv, and is linked to a phage capsid protein. After the phage infects E. coli, the single-stranded DNA replicates in the host, and the phage is reassembled and secreted into the culture medium without lysing the host E. coli. The phage is incubated with the target antigen, and the bound phage is separated, amplified, and purified. This method can easily screen a large number of clones.

Ribosome display

The technology is based on the conformation of a stable antibody-ribosomal-mRNA complex. Therefore, it is similar to phage display technology. An antibody protein is physically linked to its coding sequence. Antibody genes are transcribed, producing many mRNA molecules, each of which represents a different antibody gene. The mRNA molecule is incubated with the ribosomes of the bacteria, and then the mRNA is translated into protein, but the 3 ‘end of the mRNA molecule is still immature. Each complex displays a different antibody. After passing through an affinity column containing the target antigen, some complex that can be bound will not be washed away. This display technology is completely done in vitro and does not require cloning to complete the construction of large-scale antibody libraries.

Yeast display

Yeast display uses a pairing factor protein Aga2p to display scFv in Saccharomyces cerevisiae, and uses biotin-labeled antigens to isolate desired cells. Furthermore, real-time binding can be tracked using a fluorescently labeled antigen and flow cytometry.

This technology can generate antibodies against a variety of antigenic epitopes, but needs to be familiar with the genetic background of yeast and flow cytometry. At the same time, compared with phage display technology, the transformation efficiency is lower, and a large amount of DNA is required to construct an antibody library. But for some experts, yeast display is becoming the main technology for antibody acquisition and design.

Baculovirus display

Baculovirus has become the most common insect cell expression system due to its ability to express a large number of active proteins, and has been reported to produce 1-500 mg per liter of cells. The antibody gene is inserted downstream of the polyhedron promoter, enabling high levels of secretion into the library and cell culture. The disadvantage of this technique is that it requires careful cultivation, and insect cells need a lot of oxygen. In addition, time is a key factor in the technology.

Mammalian cell display

The advantage of expressing proteins in mammalian cells is that mammalian systems can instantly recognize antibodies. The human 293 cell line and Chinese hamster cell line are commonly used in mammalian cell antibody expression systems. However, this technology requires the use of a large number of genetic engineering techniques, and the growth of mammalian cells takes a lot of time, and the yield is not satisfactory.

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However, when to give a single dose is the key. The study found that after 30 hours of exposure to SHIV (monkey HIV), newborn cynomolgus monkeys receiving the combination of two antibodies will be prevent from being infected with the virus; if treatment is postponed to 48 Hours, it will cause the other half of newborn cynomolgus monkeys to become infected with SHIV because they received the minimum dose of antibody combination therapy. By contrast, newborn macaques receiving standard HIV therapy (antiretroviral drugs) were protected from SHIV infection when a three-week treatment regimen began 48 hours after exposure. One of the study’s author Dr. Nancy Haigwood said that these promising findings may mean that babies born to HIV-positive mothers can effectively fight HIV infection even with fewer treatments.

In this study, researchers found for the first time in non-human primates that receiving a single dose of a broad-spectrum neutralizing antibody after viral exposure could effectively inhibit SHIV infection. Previous studies have shown that receiving four doses of antibody therapy after exposure can inhibit SHIV infection; in this study, all 10 primate pups were not infected with SHIV within 6 months. Both studies used a combination of two antibodies, PGT121 and VRC07-523. Researchers point out that short-term antiretroviral therapy after viral exposure may effectively inhibit HIV transmission to newborns. Babies born to HIV-positive humans will usually receive a combination of drugs for about 6 weeks, followed by HIV test. If the test result is positive, the babies are required taking HIV drugs for life, but the research in this article shows that starting 3 weeks of antiretroviral therapy 48 hours after exposure may make non-human primates not infected with SHIV.

HIV-positive women usually receive antiretroviral treatment during their pregnancy, which can inhibit the transmission of the virus to developing babies, but sometimes HIV transmission between mothers and babies occurs, and offspring from HIV-positive mothers is usually treated by antiretroviral therapy to suppress viral infections. However, these drug mixtures can also produce many side effects, including special drug formulations for newborns. Researchers also worry about the long-term effects of antiretroviral therapy on the development of children.

Antibodies are non-toxic, and they can be modified and exist in the body for a longer period of time, which can reduce the frequency of patient treatment, so researchers want to study to clarify whether alternative or complementary antiretroviral therapies could be found in the offspring of HIV-positive mothers and adult HIV patients. Next, researchers plan to conduct further research to clarify whether different antibodies or combinations of antibodies and antiretroviral therapy can be more effective. They want to determine whether the antibody therapy they are evaluating can eliminate HIV or inhibit HIV replication.

References:

1. Shapiro, M.B., Cheever, T., Malherbe, D.C. et al. Single-dose bNAb cocktail or abbreviated ART post-exposure regimens achieve tight SHIV control without adaptive immunity. Nat Commun 11, 70 (2020) doi:10.1038/s41467-019-13972-y

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