Lab study of South African SARS-CoV-2 variant and Moderna vaccine: reduced neutralization, but still protective

As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic rages on, several virus variants have been emerging with mutations in the structural and non-structural proteins. The SARS-CoV-2 spike protein binds to the host angiotensin-converting enzyme 2 (ACE2) receptor, facilitating viral entry into the host cell. Studies have shown many different mutations in the spike protein over the last twelve months.

The first significant spike protein variant emerged with a mutation from aspartic acid (D) to glycine (G) at position 614, leading to increased viral fitness, replication, and binding to ACE2 and conformational changes within the protein. Several other variants have emerged over the past few months, raising concerns about changes to transmission, nature of the disease, and viral fitness.

When SARS-CoV-2 infects humans, our immune system rapidly responds against the viral spike protein. The receptor-binding motif in the spike protein interacts with the ACE2 receptor and is a key target of neutralization for antibodies. Longitudinal studies have found that the antibodies to the spike protein can remain in the body for at least a year following infection.

The mRNA-1273 vaccine encodes the SARS-CoV-2 spike protein and triggers a potent neutralizing antibody response to the virus that lasts for several months. The B.1.351 variant originated in South Africa has three mutations in the receptor-binding domain and many other mutations in the spike protein, all of which may influence viral binding to the ACE2 receptor and viral resistance to neutralization by antibodies.

Comparing antibody binding and viral neutralization against two different SARS-CoV-2 variants

Researchers from the US recently compared antibody binding and viral neutralization against 2 SARS-CoV-2 variants that emerged in different parts of the world. The researchers used sera from spike mRNA vaccinated and naturally infected individuals against a circulating B.1 variant and the emerging B.1.351 variant. The study is published on the preprint server bioRxiv*.

Study: Reduced binding and neutralization of infection- and vaccine-induced antibodies to the B.1.351 (South African) SARS-CoV-2 variant. Image Credit: NIAID

EHC-083E (the B.1 variant) belongs to the B.1 PANGO lineage and was isolated in March 2020 from a nasopharyngeal swab of a patient in Atlanta, GA. This variant has the D614G mutation in the viral spike protein. The B.1.351 variant was isolated in November 2020 from an oropharyngeal swab of a patient in KwaZulu-Natal, South Africa. This variant of the virus contains amino acid mutations (L18F, D80A, D215G) within the viral spike protein and deletion at positions 242-244 (L242del, A243del, and L244del), K417N, E484K, N501Y, and D614G.

Neutralizing antibodies for B.1.351 variant are produced early in the infection phase

The researchers observed decreased antibody binding to the B.1.351-derived receptor binding domain of the SARS-CoV-2 spike protein and neutralization power against the B.1.351 variant in sera from both infected and vaccinated individuals. Their longitudinal convalescent COVID-19 cohort assessed the impact on antibody binding to the receptor-binding domain and neutralization across the SARS-CoV-2 variants. Interestingly, most convalescent COVID-19 individuals showed less impact on neutralization against the B.1.351 variant at longer durations post-infection. This showed that neutralizing antibodies for the B.1.351 variant is produced early during infection and last for several months.

Most SARS-CoV-2-infected individuals showed binding and neutralizing titers against the B.1.351 variant in both acute and convalescent sera

According to the observations, most sera samples from acute and convalescent COVID-19 individuals showed antibody binding to the B.1.351-dervied receptor binding domain.  Most samples also showed a neutralizing capacity for the B.1.351 variant, and the effector functions of these neutralizing antibodies might contribute to SARS-CoV-2 infection control.

To summarize, although decreased by a few folds, most SARS-CoV-2 infected individuals showed binding and neutralizing titers against the B.1.351 variant in acute as well as convalescent sera. Moreover, all mRNA-1273 vaccinated individuals still maintained viral neutralization. These findings agree with previous notions that natural infection- and vaccine-induced immunity can offer protection against COVID-19 in the context of the SARS-CoV-2 B.1.351 variant.

“Our results show that despite few fold decrease, most infected individuals showed binding and neutralizing titers against the B.1.351 variant in acute and convalescent sera, and further, all mRNA-1273 vaccinated individuals still maintained neutralization.”

*Important Notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
  • Reduced binding and neutralization of infection- and vaccine-induced antibodies to the B.1.351 (South African) SARS-CoV-2 variant, Venkata Viswanadh Edara, Carson Norwood, Katharine Floyd, Lilin Lai, Meredith E. Davis-Gardner, William H. Hudson, Grace Mantus, Lindsay E. Nyhoff, Max W. Adelman, Rebecca Fineman, Shivan Patel, Rebecca Byram, Dumingu Nipuni Gomes, Garett Michael, Hayatu Abdullahi, Nour Beydoun, Bernadine Panganiban, Nina McNair, Kieffer Hellmeister, Jamila Pitts, Joy Winters, Jennifer Kleinhenz, Jacob Usher, James B. O’Keefe, Anne Piantadosi, Jesse J. Waggoner, Ahmed Babiker, David S. Stephens, Evan J. Anderson, Srilatha Edupuganti, Nadine Rouphael, Rafi Ahmed, Jens Wrammert, Mehul S. Suthar, bioRxiv, 2021.02.20.432046; doi: https://doi.org/10.1101/2021.02.20.432046, https://www.biorxiv.org/content/10.1101/2021.02.20.432046v1

Posted in: Medical Research News | Disease/Infection News

Tags: ACE2, Amino Acid, Angiotensin, Angiotensin-Converting Enzyme 2, Antibodies, Antibody, Aspartic Acid, Cell, Coronavirus, Coronavirus Disease COVID-19, Enzyme, Glycine, Immune System, Infection Control, Mutation, Pandemic, Protein, Receptor, Respiratory, SARS, SARS-CoV-2, Severe Acute Respiratory, Severe Acute Respiratory Syndrome, Spike Protein, Syndrome, Vaccine, Virus

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Susha Cheriyedath

Susha has a Bachelor of Science (B.Sc.) degree in Chemistry and Master of Science (M.Sc) degree in Biochemistry from the University of Calicut, India. She always had a keen interest in medical and health science. As part of her masters degree, she specialized in Biochemistry, with an emphasis on Microbiology, Physiology, Biotechnology, and Nutrition. In her spare time, she loves to cook up a storm in the kitchen with her super-messy baking experiments.

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COVID-19 vaccine candidate shows potential against SARS-CoV-2 and potential future zoonotic coronaviruses

Over the last two decades, three major outbreaks of highly pathogenic coronaviruses have occurred. The third is the ongoing coronavirus disease 2019 (COVID-19) pandemic that has claimed well over 2.46 million human lives so far, in a little over a year from its onset. Without any targeted, safe and effective antivirals to prevent or treat the infection by the causative pathogen, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), population immunity via mass vaccination seems to be the only way out – as complex and expensive as the process is likely to be.

Study: SARS-CoV-2 vaccination induces neutralizing antibodies against pandemic and pre-emergent SARS-related coronaviruses in monkeys. Image Credit: Numstocker / Shutterstock

Pan-group 2b CoV vaccine

A new study, released on the bioRxiv* preprint server, sheds light on the threat posed by future zoonotic coronaviruses to make similar leaps across species barriers to infect human beings and cause other pandemics. The goal would appear to be a vaccine capable of inducing not limited immunity against SARS-CoV-2 alone, but one that can elicit broadly neutralizing antibody and cellular immune responses against a range of other betaCoVs.

This includes existing SARS-related coronaviruses (SARSr-CoVs) in humans, as well as those that are now circulating in animals.

The first evidence that this could be so came from the observation that SARS-CoV caused the production of cross-neutralizing antibodies against many betacoronaviruses (betaCoVs). This proof-of-concept drove the search for a vaccine that would induce neutralizing antibodies against multiple group 2b Sarbecoviruses.

Cross-neutralizing antibodies

Cross-neutralizing antibodies always target the viral receptor-binding domain (RBD) via a specific epitope. The RBD can be rendered more immunogenic by using a multimeric form. One way to achieve this is by using nanoparticles to mount arrays of RBD proteins, creating a virus-like particle (VLP).

Vaccines have been shown to successfully induce cross-neutralizing antibodies against pseudoviruses expressing CoV antigens in mouse studies. The current study describes a non-human primate (NHP) study that explores the cross-neutralizing ability of a SARS-CoV-2 vaccine based on multimeric SARS-CoV-2 RBD-bearing nanoparticles.

RBD-conjugated nanoparticle vaccine

The RBD-conjugated nanoparticle vaccine comprises 24 RBD protomers on a sortase-ferritin platform for the sake of versatility. This bound not only to the human host cell receptor, the angiotensin-converting enzyme 2 (ACE2), which is thought to be the SARS-CoV-2 entry receptor, but also to potent anti-RBD neutralizing antibodies. These include DH1041, DH1042, DH1043, DH1044, and DH1045.

All these antibodies bind to epitopes within the receptor-binding motif, within the RBD. However, antibodies that bound to epitopes outside the RBD were not able to bind the RBD-bearing nanoparticle. In contrast, it did show binding to the cross-neutralizing antibody DH1047.

This vaccine was assessed by a three-dose regimen, administered at four-week intervals, in a non-human primate (NHP) study. The vaccine was found to result in high plasma levels of antibodies to the SARS-CoV-2 RBD and to the stabilized spike protein.

The antibodies completely blocked the ACE2 binding site on the spike protein after two doses of vaccine and partially blocked the binding of the RBD antibody DH104.

SARS-CoV-2 receptor binding domain (RBD) sortase conjugated nanoparticles (scNPs) elicits extremely high titers of SARS-CoV-2 pseudovirus neutralizing antibodies. a. SARS-CoV-2 RBD nanoparticles were constructed by expressing RBD with a C-terminal sortase A donor sequence (blue and red) and a Helicobacter pylori ferritin nanoparticle with N737 terminal sortase A acceptor sequences (gray) on each subunit (top left). The RBD is shown in blue with the ACE2 binding site in red. The RBD was conjugated to nanoparticles by a sortase A (SrtA) enzyme conjugation reaction (top right). The resultant nanoparticle is modeled on the bottom left. Nine amino acid sortase linker is shown in orange. Two dimensional class averages of negative stain electron microscopy images of actual RBD nanoparticles are shown on the bottom right. b. Antigenicity of RBD nanoparticles determined by biolayer interferometry against a panel of SARS-CoV-2 antibodies and the ACE2 receptor. Antibodies are color-coded based on epitope and function. N-terminal domain (NTD), nonAbs IE, infection enhancing non-neutralizing antibody; nAb, neutralizing antibody; nonAb, non-neutralizing antibody. Mean and standard error from 3 independent experiments are shown. c. Cynomolgus macaque challenge study scheme. Blue arrows indicate 748 RBD-NP immunization timepoints. Intranasal/intratracheal SARS-CoV-2 challenge is indicated at week 10. d. Macaque serum IgG binding determined by ELISA to recombinant SARS-CoV-2 stabilized Spike ectodomain (S-2P), RBD, NTD, and Fusion peptide (FP). Binding titer is shown as area752under-the curve of the log10-transformed curve. Arrows indicate immunization timepoints. e. Plasma antibody blocking of SARS-CoV-2 S-2P binding to ACE2-Fc and RBD neutralizing antibody DH1041. Group mean and standard error are shown. f. Dose-dependent serum neutralization of SARS-COV-2 pseudotyped virus infection of ACE2- expressing 293T cells. Serum was collected after two immunizations. The SARS-CoV-2 pseudovirus spike has an aspartic acid to glycine change at position 614 (D614G). Each curve represents a single macaque. g. Heat map of serum neutralization ID50 and ID80 titers for SARS-COV-2 D614G pseudotyped virus after two immunizations. h. SARS-COV-2 D614G pseudotyped virus serum neutralization kinetics. Each curve represents a single macaque. i. Comparison of serum neutralization ID50 titers from cynomolgus macaques immunized with recombinant protein RBD nanoparticles (blue) or nucleoside-modified mRNA-LNP expressing S- 2P (burgundy) (**P<0.01, Two-tailed Exact Wilcoxon test n = 5). j. Comparison of serum neutralization titers obtained from RBD-scNP-vaccinated macaques (blue) and SARS-CoV-2 infected humans (shades of green). Human samples were stratified based on disease severity as asymptomatic (N=34), symptomatic (n=71), and hospitalized (N=60) (**P<0.01, Two-tailed Wilcoxon test n = 5).

Competitive with the Moderna/Pfizer vaccine for neutralizing antibody titer

When tested against the currently dominant D614G strain of SARS-CoV-2, the RBD-conjugated nanoparticle vaccine induced higher neutralizing antibody titers than another vaccine similar to the Moderna and Pfizer lipid-encapsulated nucleoside-modified mRNA (mRNA-LNP) vaccines that are now being used in the vaccination campaigns against COVID-19.

The measure of antibody titer used here showed an eight-fold increase with the former compared to the latter. The antibody response was also higher with the RBD-nanoparticle vaccine than with natural infection of all grades of severity.

Unaffected by emerging variants

It also showed potent neutralizing activity against the new SARS-CoV-2 variant B.1.1.7, which is rapidly spreading worldwide. This is not only more infective but may be resistant to many RBD-targeting antibodies, as well as more virulent.

While changes in binding affinity of anti-RBD antibody DH1041 to the ACE2 receptor and to the spike protein were observed with different mutations, such as those acquired during mink infection, or those found in the South African or Brazil or UK strains, the cross-neutralizing antibody DH1047 showed unchanged binding to the SARS-CoV-2.

“RBD-scNP (RBD sortase A conjugated nanoparticle) and mRNA-LNP-induced RBD binding antibodies were not sensitive to spike mutations present in neutralization-resistant UK, South Africa or Brazil SARS-CoV-2 variants.”

SARS-CoV-2 spike induces cross-neutralizing antibodies to pre-emergent betaCoVs

SARSr-CoVs still pose a danger of future pandemics to human beings. The researchers, therefore, explored the ability of this vaccine to neutralize other viruses. Similar to the LNP-mRNA vaccines based on the prefusion stabilized spike or the RBD, the RBD-scNP also elicited potent cross-neutralizing antibodies against SARS-CoV and SARSr-bat CoVs (batCoV-WIV-1, and batCoV-SHC014).

The neutralization was most potent against SARS-CoV-2, however. The highest neutralizing antibody titers were observed with RBD-scNP and the least with the RBD-expressing LNP-mRNA vaccine. The high titers may indicate that durable immunity is achieved.  

The RBD-scNP vaccine showed cross-neutralizing activity against batCoV-RaTG13 and pangolin CoV GXP4L spike antigens, in addition to SARS-CoV and SARS-CoV-2. Notably, sera obtained following vaccination with this formulation failed to neutralize the seasonal human CoVs or MERS-CoV, probably because of the difference in RBD among these CoVs, which belong to different groups.

The similarity between the RBD-scNP and DH1047 in terms of cross-neutralizing profile shows that not only do antibodies induced by the former bind near the epitope bound by the latter, but they are not specific to SARS-CoV-2 RBD. In fact, they also block batCoV-SHC01.

Notably, only a third of COVID-19 patients produce antibodies that block DH1047, indicating it is a sub-immunodominant epitope. As such, the RBD-scNP vaccine targets this epitope rather than the immunodominant ACE2 blocking epitope.

Protection against productive infection

The RBD-scNP vaccine was also protective for vaccinated monkeys when challenged with the SARS-CoV-2 virus via the respiratory tract. In all but one of the vaccinated macaques, “RBD-scNP-induced immunity prevented virus replication, and likely provided sterilizing immunity, in the upper and lower respiratory tract.”

What are the implications?

The RBD-scNP platform induced the highest cross-neutralizing antibody titer for group 2b CoVs, and as such, may serve as the basis for a reasonably effective initial broadly neutralizing vaccine against this group – both now, and in the future, if the further zoonotic transmission should occur.

The study also showed that the use of both RBD-scNP and the LNP-spike mRNA vaccines, the latter resembling those which have been recently rolled out, is capable of inducing cross-neutralizing antibodies to the dominant D614G variant and the newer variants of SARS-CoV-2, but at lower titers.

The findings indicate the ability of the SARS-CoV-2 Spike to be included in an RBD-scNP or LNP-mRNA formulation to induce cross-neutralizing antibodies against several SARSr-CoVs. Thus, even the currently used vaccines are likely to prevent future pandemics if immunization is successfully achieved.

*Important Notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
  • Saunders, K. O. et al. (2021). SARS-CoV-2 vaccination induces neutralizing antibodies against pandemic and pre-emergent SARS-related coronaviruses in monkeys. bioRxiv preprint. doi: https://doi.org/10.1101/2021.02.17.431492. https://www.biorxiv.org/content/10.1101/2021.02.17.431492v1

Posted in: Medical Science News | Medical Research News | Disease/Infection News | Healthcare News

Tags: ACE2, Amino Acid, Angiotensin, Angiotensin-Converting Enzyme 2, Antibodies, Antibody, Aspartic Acid, binding affinity, Cell, Conjugation, Coronavirus, Coronavirus Disease COVID-19, Electron, Electron Microscopy, Enzyme, Glycine, heat, Helicobacter pylori, Immunization, MERS-CoV, Microscopy, Nanoparticle, Nanoparticles, Nucleoside, Pandemic, Pathogen, Protein, Pseudovirus, Receptor, Respiratory, SARS, SARS-CoV-2, Severe Acute Respiratory, Severe Acute Respiratory Syndrome, Spike Protein, Syndrome, Vaccine, Virus

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Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.

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Substrain of SARS-CoV-2 variant in UK may resist antibody neutralization

Researchers at the Polish Academy of Sciences in Warsaw have identified a substrain of the recently emerged B.1.1.7 variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that may confer resistance to antibody neutralization.

The SARS-CoV-2 virus is the agent responsible for the coronavirus disease 2019 (COVID-19) pandemic that has now claimed the lives of more than 2.35 million people.

The substrain of the B.1.1.7 variant of concern (VOC) contains mutations that have previously been shown to compromise the binding of neutralizing antibodies.

Tomasz Lipniacki and colleagues say mutations in the receptor-binding domain (RBD) of the viral spike protein are of particular concern, especially those identified in the receptor-binding motif (RBM).

The spike protein is the surface structure the virus uses to bind to and infect cells by attaching to the host cell receptor angiotensin-converting enzyme 2 (ACE2).

The researchers say the mutations could eventually lead to “immune escape” strains that can reinfect convalescent individuals and reduce the efficacy of the vaccines currently being used in mass immunization efforts.

“Such mutants may hinder the efficiency of existing vaccines and expand in response to the increasing after‐infection or vaccine‐induced seroprevalence,” writes the team.

A pre-print version of the research paper is available on the medRxiv* server, while the article undergoes peer review.

Study: L18F substrain of SARS-CoV-2 VOC-202012/01 is rapidly spreading in England. Image Credit: NIAID

The B.1.1.7 variant has spread rapidly since mid-October 2020

The B.1.1.7 variant has rapidly spread since mid-October 2020, and by January 2021, it constituted about 80% of all SARS-CoV-2 genomes sequenced in England.

The high transmissibility of this VOC may be expressed in terms of its replicative advantage – defined as the ratio of the VOC reproduction number to that of non-VOC strains.

To date, a number of studies have estimated the replicative advantage as lying somewhere between 1.47 and 2.24.

As is the case with all viral strains, the B.1.1.7 variant will continue to mutate, and given its significant replicative advantage, any mutations acquired are likely to spread globally.

“As this strain will likely spread globally towards fixation, it is important to monitor its molecular evolution,” say the researchers.

What did the current study involve?

Using the Global Initiative on Sharing Avian Influenza Data (GISAID) database, Lipniacki and colleagues estimated growth rates of the mutations that B.1.1.7 has acquired.

This revealed a substrain with an L18F substitution in the spike protein that is rapidly growing in the UK.

This leucine‐to‐phenylalanine substitution in residue 18 was first reported to have occurred in a VOC strain genome collected on December 4th, 2020.

As of February 5th, 2021, as many as 850 spikes L18F VOC genomes had been reported in England.

Based on data collected between December 7th, 2020 and January 17th, 2021, the researchers showed that the L18F substrain had spread exponentially in England. They estimated a replicative advantage of 1.70 relative to the remaining B.1.1.7 substrains.

RBM mutations are particularly concerning

Lipniacki and colleagues say that mutations in the RBD of the spike protein are particularly concerning, especially substitutions E484K and S494P found in the RBM.

Importantly, the LI8F mutation has expanded in the South African variant 501Y.V2 that contains the spike mutations E484K and N501Y. Studies have suggested that E484K may compromise the binding of class 2 neutralizing antibodies, while the A501V mutation compromises the binding of class 1 antibodies.

Furthermore, in a 2021 study published in Science, the S494P substitution was characterized as an escape mutation, along with six other escape residues in the RBM that included F490.

In the current study, Lipniacki and colleagues also identified F490S as a potential escape mutation.

What do the authors advise?

“These mutations may potentially lead to immune escape mutants, resulting in reinfection of convalescent individuals and lowering efficacy of current vaccines,” warn the researchers.

“Propagation of such mutations is facilitated by high replicative advantage of the VOC strain and potential selection due to the increasing number of convalescent or immunized individuals,” they add.

Correspondingly, a study published in 2021 showed that L18F substitution compromises the binding of neutralizing antibodies, suggesting that the replicative advantage of L18F mutants may be partly associated with the ability to infect seroprevalent individuals (who already have anti-SARS-CoV-2 antibodies).

“In turn, propagation of mutations in escape residues (L18, E484, F490S, or S494) on the VOC strain suggests an increasing selection pressure resulting from the growth of the seroprevalent fraction of the population of England,” says Lipniacki and colleagues.

“This trend can be enhanced by the ongoing English vaccination program, in which the relatively large time span between the first and second dose can be a contributing factor,” concludes the team.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
  • Lipniacki T, et al. L18F substrain of SARS-CoV-2 VOC-202012/01 is rapidly spreading in England. medRxiv, 2021. doi: https://doi.org/10.1101/2021.02.07.21251262, https://www.medrxiv.org/content/10.1101/2021.02.07.21251262v1

Posted in: Medical Research News | Disease/Infection News

Tags: ACE2, Angiotensin, Angiotensin-Converting Enzyme 2, Antibodies, Antibody, Avian Influenza, Cell, Coronavirus, Coronavirus Disease COVID-19, Efficacy, Enzyme, Evolution, Genome, Immunization, Influenza, Leucine, Mutation, Pandemic, Phenylalanine, Propagation, Protein, Receptor, Reproduction, Research, Respiratory, SARS, SARS-CoV-2, Severe Acute Respiratory, Severe Acute Respiratory Syndrome, Spike Protein, Syndrome, Vaccine, Virus

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Sally Robertson

Sally has a Bachelor's Degree in Biomedical Sciences (B.Sc.). She is a specialist in reviewing and summarising the latest findings across all areas of medicine covered in major, high-impact, world-leading international medical journals, international press conferences and bulletins from governmental agencies and regulatory bodies. At News-Medical, Sally generates daily news features, life science articles and interview coverage.

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NIH launches trial of antibody drugs against COVID-19

(HealthDay)—A study to assess whether certain approved or experimental drugs are effective against COVID-19 and warrant testing in large clinical trials has been launched by the U.S. National Institutes of Health (NIH).

The research will largely focus on monoclonal antibody medications. These types of drugs garnered headlines last week as President Donald Trump credited one such drug cocktail, made by Regeneron, with helping him recover from his coronavirus infection.

However, the therapy is not yet approved against COVID-19 and is still considered experimental.

“The goal here is to identify as quickly as possible the experimental therapeutics that demonstrate the most clinical promise as COVID-19 treatments and move them into larger-scale testing,” said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID).

According to the NIH, the new phase 2 study will enroll adults hospitalized with COVID-19 at as many as 40 U.S sites and is being conducted by NIAID.

The study will assess the approved monoclonal antibody risankizumab in conjunction with the antiviral drug remdesivir, compared to a placebo plus remdesivir. It will also test the experimental monoclonal antibody lenzilumab with remdesivir, compared to placebo and remdesivir.

Remdesivir has shown benefits for patients with severe COVID-19—so severe they needed supplemental oxygen—and is now considered standard of care for hospitalized COVID-19 patients, the NIH said.

Monoclonal antibodies are laboratory versions of proteins naturally produced by the immune system in response to invading viruses or other pathogens. Some are already approved for non-COVID uses: Risankizumab received U.S. Food and Drug Administration approval in 2019 for the treatment of severe plaque psoriasis.

Lenzilumab is currently being tested separately in a phase 3 COVID-19 study, and in a phase 1b/2 study as sequenced therapy along with CAR-T treatments.

About 100 volunteers will be assigned to each study arm, with each of the study sites testing no more than three treatments at once.

The new study “aims to streamline the pathway to finding urgently needed COVID-19 treatments,” NIH Director Dr. Francis Collins explained in an NIH news release. That might be accomplished “by repurposing either licensed or late-stage-development medicines and testing them in a way that identifies the most promising agents for larger clinical studies in the most expedient way possible,” he said.

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Could Regeneron’s antibody cocktail help President Trump?

‘If Trump recovers quickly, that will mitigate downside loss on Wall Street’: Stuart Varney

On Friday, the White House revealed that President Trump was given a dose of an antibody cocktail following his coronavirus diagnosis.

According to a statement from White House press secretary Kayleigh McEnany, Trump received an 8-gram dose of the polyclonal antibody cocktail, REGN-COV2, from pharmaceutical company Regeneron, as a “precautionary measure.”

Before the announcement, Dr. Matt McCarthy, an infectious disease doctor, told FOX Business’s Stuart Varney that the Regeneron antibody cocktail would be the first thing he would have recommended for the president.

“If I got brought in today to the Oval Office, first thing I’d say is, has anyone reached out to Regeneron?” McCarthy said. “Has anyone talked about an antibody cocktail for him? Three days ago, the company showed that they can reduce the amount of virus in the body and that they can decrease the duration of symptoms.”

TRUMP, FIRST LADY EXPERIENCING ‘MILD SYMPTOMS’ AS WH DOC RELEASES DETAILS ABOUT TREATMENT

Regeneron declined to comment on the specifics of giving a dose of its antibody cocktail to the president.

“As a general policy, Regeneron has a compassionate use program with certain established criteria and a review committee,” the company said in a statement. “Also as a matter of policy, we don’t identify individuals without their consent who have or have not submitted a request or who are participating in our clinical trials.”

LINCOLN PROJECT WISHES TRUMP WELL, HOPES CORONAVIRUS DIAGNOSIS ‘SENDS A SIGNAL’ TO HIS SUPPORTERS

“For REGN-COV2, our first priority is to maintain a sufficient supply in order to conduct rigorous clinical trials,” the company added. “In addition to the clinical trial supply, there is limited product available for compassionate use requests that are approved under certain exceptional circumstances on a case-by-case basis.”

AFTER TRUMP COVID DIAGNOSIS, PENTAGON SAYS ALERT LEVELS REMAIN UNCHANGED

McEnany’s statement also mentioned that the president has been taking “zinc, vitamin D, famotidine, melatonin and a daily aspirin.”

“As of this afternoon, the President remained fatigued but in good spirits,” the statement said. “He’s being evaluated by a team of experts, and together we’ll be making recommendations to the President and First Lady in regards to next best steps.”

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McCarthy told Stuart Varney that regardless of statistics, the coronavirus is “unpredictable.”

“Anyone who tells you they know what’s going to happen or anyone who tells you that, oh, he’ll probably be fine, I don’t want that person making decisions for the president of the United States,” McCarthy said. “The key here is to watch how things evolve over the next few days.”

“We see patients all the time in his demographic that feel relatively well for a week and then a week later, they’re in the hospital,” he added. “That’s not to say that’s what’s going to happen here. In fact, no one knows what’s going to happen here. But the key is to keep an eye on his vital signs and, in particular, the amount of oxygen that he has. So if his oxygen saturation starts dropping, that should raise alarm bells that he needs to be headed to a more intensive monitoring system.”

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Study takes us a step closer to a universal antibody test for COVID-19

A new study released by Houston Methodist takes researchers a significant step closer to developing a uniform, universal COVID-19 antibody test. The multicenter collaboration tested alternative ways to measure COVID-19 antibody levels that is faster and easier and can inexpensively be used on a larger scale to accurately identify potential donors with the best chance of helping patients infected with the SARS-CoV-2 virus with convalescent plasma therapy.

The findings will also have applications beyond determining who the best plasma donors are. The consensus among the study authors is that, following donor identification, it will most likely next be used in practice to establish target levels of COVID-19 antibodies individuals will need to be considered candidates for vaccines and passive immune therapies.

Additional uses coming later that are likely to have the biggest societal impact, the researchers say, are to assess relative immunity in those previously infected by the SARS-CoV-2 virus and identifying asymptomatic individuals with high levels of neutralizing antibodies against SARS-CoV-2.

It was also found that donors who experienced shortness of breath (or dyspnea) while infected with COVID-19 and those who were hospitalized or had severe disease were more likely to have a robust immune response and, thus, had higher levels of neutralizing antibodies in all the tests. In the absence of available testing, identifying such donor characteristics may be used as a contingency plan to determine which patients have developed higher antibody levels and inform efforts to recruit plasma donors for therapeutic purposes.

In collaboration with Penn State, University of Texas at Austin and U.S. Army Medical Research Institute of Infectious Diseases, study authors James M. Musser, M.D., Ph.D., and Eric Salazar, M.D., Ph.D., physician scientists at Houston Methodist, sought to find alternatives to measuring virus neutralization (VN) titers, which is the gold standard of COVID-19 antibody testing, as VN antibodies in the blood correlate with immunity. This kind of antibody testing, however, is not widely available, because it’s technically complex, requires days to set up, run and interpret, and needs to be performed in a biosafety level 3 laboratory. This leads to most donor plasma virus antibody levels remaining unknown prior to transfusions, so an easier, more readily available method is needed to identify more suitable convalescent plasma donors.

The research team, therefore, looked to another type of test, called ELISA assays, which can be implemented and performed with relative ease in a high-throughput fashion and are widely available and extensively used in clinical labs across the world. The ELISA tests, or enzyme-linked immunosorbent assays, look at whether antibodies against the SARS-CoV-2 proteins are present and produce a quantitative measure of those antibodies. The UT Austin research team developed the ELISA antibody test for SARS-CoV-2 and provided the viral antigens for this study.

Specifically, scientists looked at the relationship of anti-spike ectodomain (ECD) and anti-receptor binding domain (RBD) IgG bloodstream antibody titers. The spike ECD and RBD proteins are physiological parts of the much-talked-about spike protein made by SARS-CoV-2 and critical to how the virus finds its way into the body, spreads and causes COVID-19 disease, so they are prime targets for antibody testing and vaccine development. The blood samples for the study were identified during an institutional surveillance program involving 2,814 Houston Methodist employees.

The goal of the study was to test the hypothesis that anti-ECD and anti-RBD IgG bloodstream antibody titers are correlated with VN titer, making these more accessible, easier-to-perform ELISA tests a surrogate marker to identify plasma donors with titers above the recommended U.S. Food and Drug Administration threshold for convalescent plasma donation.

In assessing the correlation between VN antibody levels and anti-RBD and anti-ECD ELISA protein titer data, the researchers found that the ELISA tests had an 80% probability or greater of comparable antibody level to VN titers at or above the FDA-recommended levels for COVID-19 convalescent plasma. These results affirm that all three types of tests could potentially serve as a quantitative target for therapeutic and prophylactic treatments.

They also found that convalescent donors maintain high levels of immunity over the course of many weeks and that frequent plasma donations did not cause a significant decrease in antibody or virus neutralization levels.

Perhaps most surprising is that they also identified 27 individuals from the surveillance cohort with high enough antibody titers across all three tests to indicate that some asymptomatic individuals may have plasma suitable for therapeutic use and may have a degree of relative immunity against SARS-CoV-2.

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