Tag Archives: COVID-19

Microbiology

Novel subset of memory B cells predicts long-lived antibody responses to influenza vaccination

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Reviewed by Emily Henderson, B.Sc.Mar 22 2023

Memory B cells play a critical role to provide long-term immunity after a vaccination or infection. In a study published in the journal Immunity, researchers describe a distinct and novel subset of memory B cells that predict long-lived antibody responses to influenza vaccination in humans.

These effector memory B cells appear to be poised for a rapid serum antibody response upon secondary challenge one year later, Anoma Nellore, M.D., Fran Lund, Ph.D., and colleagues at the University of Alabama at Birmingham and Emory University report. Evidence from transcriptional and epigenetic profiling shows that the cells in this subset differ from all previously described memory B cell subsets.

The UAB researchers identified the novel subset by the presence of FcRL5 receptor protein on the cell surface. In immunology, a profusion of different cell-surface markers is used to identify and separate immune-cell types. In the novel memory B cell subset, FcRL5 acts as a surrogate marker for positive expression of the T-bet transcription factor inside the cells. Various transcription factors act as master regulators to orchestrate the expression of many different gene sets as various cell types grow and differentiate.

Nellore, Lund and colleagues found that the FcRL5+ T-bet+ memory B cells can be detected seven days after immunization, and the presence of these cells correlates with vaccine antibody responses months later. Thus, these cells may represent an early, easily monitored cellular compartment that can predict the development of a long-lived antibody response to vaccines.

This could be a boon to the development of a more effective yearly influenza vaccine. “New annual influenza vaccines must be tested, and then manufactured, months in advance of the winter flu season,” Lund said. “This means we must make an educated guess as to which flu strain will be circulating the next winter.”

Why are vaccine candidates made so far in advance? Pharmaceutical companies, Lund says, need to wait many weeks after vaccinating volunteers to learn whether the new vaccine elicits a durable immune response that will last for months. “One potential outcome of the current study is we may have identified a new way to predict influenza vaccine durability that would give us an answer in days, rather than weeks or months,” Lund said. “If so, this type of early ‘biomarker’ could be used to test flu vaccines closer to flu season -; and moving that timeline might give us a better shot at predicting the right flu strain for the new annual vaccine.”

Seasonal flu kills 290,000 to 650,000 people each year, according to World Health Organization estimates. The global flu vaccine market was more than $5 billion in 2020.

To understand the Immunity study, it is useful to remember what happens when a vaccinated person subsequently encounters a flu virus.

Following exposure to previously encountered antigens, such as the hemagglutinin on inactivated influenza in flu vaccines, the immune system launches a recall response dominated by pre-existing memory B cells that can either produce new daughter cells or cells that can rapidly proliferate and differentiate into short-lived plasmablasts that produce antibodies to decrease morbidity and mortality. These latter B cells are called “effector” memory B cells.

“The best vaccines induce the formation of long-lived plasma cells and memory B cells,” said Lund, the Charles H. McCauley Professor in the UAB Department of Microbiology and director of the Immunology Institute. “Plasma cells live in your bone marrow and make protective antibodies that can be found in your blood, while memory B cells live for many years in your lymph nodes and in tissues like your lungs.

“Although plasma cells can survive for decades after vaccines like the measles vaccine, other plasma cells wane much more quickly after vaccination, as is seen with COVID-19,” Lund said. “If that happens, memory B cells become very important because these long-lived cells can rapidly respond to infection and can quickly begin making antibody.”

In the study, the UAB researchers looked at B cells isolated from blood of human volunteers who received flu vaccines over a span of three years, as well as B cells from tonsil tissue obtained after tonsillectomies.

They compared naïve B cells, FcRL5+ T-bet+ hemagglutinin-specific memory B cells, FcRL5neg T-betneg hemagglutinin-specific memory B cells and antibody secreting B cells, using standard phenotype profiling and single-cell RNA sequencing. They found that the FcRL5+ T-bet+ hemagglutinin-specific memory B cells were transcriptionally similar to effector-like memory cells, while the FcRL5neg T-betneg hemagglutinin-specific memory B cells exhibited stem-like central memory properties.

Antibody-secreting B cells need to produce a lot of energy to churn out antibody production, and they also must turn on processes that protect the cells from some of the detrimental side effects of that intense metabolism, including controlling the dangerous reactive oxygen species and boosting the unfolded protein response.

The FcRL5+ T-bet+ hemagglutinin-specific memory B cells did not express the plasma cell commitment factor, but did express transcriptional, epigenetic and metabolic functional programs that poised these cells for antibody production. These included upregulated genes for energy-intensive metabolic processes and cellular stress responses.

Accordingly, FcRL5+ T-bet+ hemagglutinin-specific memory B cells at Day 7 post-vaccination expressed intracellular immunoglobulin, a sign of early transition to antibody-secreting cells. Furthermore, human tonsil-derived FcRL5+ T-bet+ memory B differentiated more rapidly into antibody-secreting cells in vitro than did FcRL5neg T-betneg hemagglutinin-specific memory B cells.

Lund and Nellore, an associate professor in the UAB Department of Medicine Division of Infectious Diseases, are co-corresponding authors of the study, “A transcriptionally distinct subset of influenza-specific effector memory B cells predicts long-lived antibody responses to vaccination in humans.”

Co-authors with Lund and Nellore are Esther Zumaquero, R. Glenn King, Betty Mousseau, Fen Zhou and Alexander F. Rosenberg, UAB Department of Microbiology; Christopher D. Scharer, Tian Mi, Jeremy M. Boss, Christopher M. Tipton and Ignacio Sanz, Emory University School of Medicine, Atlanta, Georgia; Christopher F. Fucile, UAB Informatics Institute; John E. Bradley and Troy D. Randall, UAB Department of Medicine, Division of Clinical Immunology and Rheumatology; and Stuti Mutneja and Paul A. Goepfert, UAB Department of Medicine Division of Infectious Diseases.

Funding for the work came from National Institutes of Health grants AI125180, AI109962 and AI142737 and from the UAB Center for Clinical and Translational Science.

Source:

University of Alabama at Birmingham

Journal reference:

Nellore, A., et al. (2023). A transcriptionally distinct subset of influenza-specific effector memory B cells predicts long-lived antibody responses to vaccination in humans. Immunity. doi.org/10.1016/j.immuni.2023.03.001.

Microbiology

Nasal Vaccines: Stopping the COVID-19 Virus Before It Reaches the Lungs

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The Pfizer-BioNTech and Moderna mRNA vaccines have played a large role in preventing deaths and severe infections from COVID-19. But researchers are still in the process of developing alternative approaches to vaccines to improve their effectiveness, including how they’re administered. Immunologist and microbiologist Michael W. Russell of the University at Buffalo explains how nasal vaccines work, and where they are in the development pipeline.

The immune system has two distinct components: mucosal and circulatory.

The mucosal immune system provides protection at the mucosal surfaces of the body. These include the mouth, eyes, middle ear, the mammary and other glands, and the gastrointestinal, respiratory, and urogenital tracts. Antibodies and a variety of other anti-microbial proteins in the sticky secretions that cover these surfaces, as well as immune cells located in the lining of these surfaces, directly attack invading pathogens.

The circulatory part of the immune system generates antibodies and immune cells that are delivered through the bloodstream to the internal tissues and organs. These circulating antibodies do not usually reach the mucosal surfaces in large enough amounts to be effective. Thus mucosal and circulatory compartments of the immune system are largely separate and independent.

The immune components people may be most familiar with are proteins known as antibodies, or immunoglobulins. The immune system generates antibodies in response to invading agents that the body identifies as “non-self,” such as viruses and bacteria.

Antibodies bind to specific antigens: the part or product of a pathogen that induces an immune response. Binding to antigens allows antibodies to either inactivate them, as they do with toxins and viruses, or kill bacteria with the help of additional immune proteins or cells.

The mucosal immune system generates a specialized form of antibody called secretory IgA, or SIgA. Because SIgA is located in mucosal secretions, such as saliva, tears, nasal and intestinal secretions, and breast milk, it is resistant to digestive enzymes that readily destroy other forms of antibodies. It is also superior to most other immunoglobulins at neutralizing viruses and toxins, and at preventing bacteria from attaching to and invading the cells lining the surfaces of organs.

There are also many other key players in the mucosal immune system, including different types of anti-microbial proteins that kill pathogens, as well as immune cells that generate antibody responses.

Mucus is one of the central secretions of the mucosal immune system.

Almost all infectious diseases in people and other animals are acquired through mucosal surfaces, such as by eating or drinking, breathing or sexual contact. Major exceptions include infections from wounds, or pathogens delivered by insect or tick bites.

The virus that causes COVID-19, SARS-CoV-2, enters the body via droplets or aerosols that get into your nose, mouth, or eyes. It can cause severe disease if it descends deep into the lungs and causes an overactive, inflammatory immune response.

This means that the virus’s first contact with the immune system is probably through the surfaces of the nose, mouth, and throat. This is supported by the presence of SIgA antibodies against SARS-CoV-2 in the secretions of infected people, including their saliva, nasal fluid, and tears. These locations, especially the tonsils, have specialized areas that specifically trigger mucosal immune responses.

Some research suggests that if these SIgA antibody responses form as a result of vaccination or prior infection, or occur quickly enough in response to a new infection, they could prevent serious disease by confining the virus to the upper respiratory tract until it is eliminated.

Vaccines can be given through mucosal routes via the mouth or nose. This induces an immune response through areas that stimulate the mucosal immune system, leading mucosal secretions to produce SIgA antibodies.

There are several existing mucosal vaccines, most of them taken by mouth. Currently, only one, the flu vaccine, is delivered nasally.

In the case of nasal vaccines, the viral antigens intended to stimulate the immune system would be taken up by immune cells within the lining of the nose or tonsils. While the exact mechanisms by which nasal vaccines work in people have not been thoroughly studied, researchers believe they work analogously to oral mucosal vaccines. Antigens in the vaccine induce B cells in mucosal sites to mature into plasma cells that secrete a form of IgA. That IgA is then transported into mucosal secretions throughout the body, where it becomes SIgA.

If the SIgA antibodies in the nose, mouth or throat target SARS-CoV-2, they could neutralize the virus before it can drop down into the lungs and establish an infection.

Nasal vaccines could provide a more approachable alternative to injections for patients leery of needles.

I believe that arguably the best way to protect an individual against COVID-19 is to block the virus at its point of entry, or at least to confine it to the upper respiratory tract, where it might inflict relatively little damage.

Breaking chains of viral transmission is crucial to controlling epidemics. Researchers know that COVID-19 spreads during normal breathing and speech, and is exacerbated by sneezing, coughing, shouting, singing and other forms of exertion. Because these emissions mostly originate from saliva and nasal secretions, where the predominant form of antibody present is SIgA, it stands to reason that secretions with a sufficiently high level of SIgA antibodies against the virus could neutralize and thereby diminish its transmissibility.

Existing vaccines, however, do not induce SIgA antibody responses. Injected vaccines primarily induce circulating IgG antibodies, which are effective in preventing serious disease in the lungs. Nasal vaccines specifically induce SIgA antibodies in nasal and salivary secretions, where the virus is initially acquired, and can more effectively prevent transmission.

Nasal vaccines may be a useful supplement to injected vaccines in hot spots of infection. Since they don’t require needles, they might also help overcome vaccine hesitancy due to fear of injections.

There have been over 100 oral or nasal COVID-19 vaccines in development around the world.

Most of these have been or are currently being tested in animal models. Many have reported successfully inducing protective antibodies in the blood and secretions, and have prevented infection in these animals. However, few have been successfully tested in people. Many have been abandoned without fully reporting study details.

According to the World Health Organization, 14 nasal COVID-19 vaccines are in clinical trials as of late 2022. Reports from China and India indicate that nasal or inhaled vaccines have been approved in these countries. But little information is publicly available about the results of the studies supporting approval of these vaccines.

Written by Michael W. Russell, Professor Emeritus of Microbiology and Immunology, University at Buffalo.

This article was first published in The Conversation.The Conversation

Michael W. Russell, University at Buffalo

Microbiology

Low-cost, universal oral COVID-19 vaccine prevents severe respiratory illness in hamsters

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Reviewed by Emily Henderson, B.Sc.Mar 22 2023

A UCLA-led team has developed an inexpensive, universal oral COVID-19 vaccine that prevented severe respiratory illness and weight loss when tested in hamsters, which are naturally susceptible to SARS-CoV-2. It proved as effective as vaccines administered by injection or intranasally in the research.

If ultimately approved for human use, it could be a weapon against all COVID-19 variants and boost uptake, particularly in low- and middle-income countries, and among those with an aversion to needles.

The study is published in the peer-reviewed journal Microbiology Spectrum.

The oral vaccine is based primarily on the nucleocapsid protein, which is the most abundantly expressed of the virus’s four major structural proteins and evolves at a much slower rate than the frequently mutating spike protein. The vaccine utilizes a highly weakened bacterium to produce the nucleocapsid protein in infected cells as well as the membrane protein, which is another highly abundant viral structural protein.

Being a universal vaccine based primarily upon the nucleocapsid protein, the vaccine is resistant to the incessant mutations of the SARS-CoV-2 spike protein upon which virtually all current vaccines are based. As a result, current vaccines rapidly become obsolete, requiring that they repeatedly be re-engineered. Hence, our vaccine should protect against new and emerging variants of SARS-CoV-2.”

Dr. Marcus Horwitz, senior author, distinguished professor of medicine in the Division of Infectious Diseases and of microbiology, immunology and molecular genetics at the David Geffen School of Medicine at UCLA

Oral delivery also makes it easier to distribute the vaccine in resource poor areas of the world by eliminating the need for needles, syringes, and trained personnel to deliver injectable vaccines, he added. “An oral vaccine may also be attractive to many people with vaccine hesitancy on account of fear of needles.”

The researchers noted that while it worked exceptionally well in preventing severe respiratory illness, it did not provide full protection against high viral loads in the hamsters. Also, they did not test it against the Omicron strain, which contains a nearly identical nucleocapsid protein, because of this strain’s low virulence in the golden Syrian hamsters they used.

But the vaccine, they write, “is efficacious when administered via the oral route against COVID-19-like disease in a highly demanding animal model. This conveniently administered, easily manufactured, inexpensive, and readily stored and transported vaccine could play a major role in ending the COVID-19 pandemic by protecting immunized individuals from serious disease from current and future strains of SARS-CoV-2.”

The next step in the process will be to manufacture the vaccine for oral administration via an acid-resistant enteric capsule that will allow the vaccine to be safely released in the small intestine, Horwitz said. It will then be tested for safety, immunogenicity, and efficacy in humans.

“We also plan to expand the vaccine to protect against infections caused by other types of potentially pandemic coronaviruses such as the virus that causes Middle Eastern Respiratory Syndrome (MERS),” he added.

Additional authors are Qingmei Jia and Saša Masleša-Galić of UCLA; Helle Bielefeldt-Ohmann of the University of Queensland, Australia; and Rachel Maison, Airn Hartwig, and Richard Bowen of Colorado State University.

This study was supported by a Corona Virus Seed grant from the UCLA AIDS Institute and Charity Treks and by the National Institutes of Health (AI141390).

Source:

UCLA Health

Journal reference:

Jia, Q., et al. (2023). Oral Administration of Universal Bacterium-Vectored Nucleocapsid-Expressing COVID-19 Vaccine is Efficacious in Hamsters. Microbiology Spectrum. doi.org/10.1128/spectrum.05035-22.

Microbiology

Co-infection with MRSA ‘superbug’ could make COVID-19 outcomes even more deadly

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Reviewed by Emily Henderson, B.Sc.Mar 21 2023

Global data shows nearly 10 per cent of severe COVID-19 cases involve a secondary bacterial co-infection – with Staphylococcus aureus, also known as Staph A., being the most common organism responsible for co-existing infections with SARS-CoV-2. Researchers at Western have found if you add a ‘superbug’ – methicillin-resistant Staphylococcus aureus (MRSA) – into the mix, the COVID-19 outcome could be even more deadly.

The mystery of how and why these two pathogens, when combined, contribute to the severity of the disease remains unsolved. However, a team of Western researchers has made significant progress toward solving this “whodunit”.

New research by Mariya Goncheva, Richard M. Gibson, Ainslie C. Shouldice, Jimmy D. Dikeakos and David E. Heinrichs, has revealed that IsdA, a protein found in all strains of Staph A., enhanced SARS-CoV-2 replication by 10- to 15-fold. The findings of this study are significant and could help inform the development of new therapeutic approaches for COVID-19 patients with bacterial co-infections.

Interestingly, the study, which was recently published in iScience, also showed that SARS-CoV-2 did not affect the bacteria’s growth. This was contrary to what the researchers had initially expected.

We started with an assumption that SARS-CoV-2 and hospitalization due to COVID-19 possibly caused patients to be more susceptible to bacterial infections which eventually resulted in worse outcomes.”

Mariya Goncheva

Goncheva is a former postdoctoral associate, previously with the department of microbiology and immunology at Schulich School of Medicine & Dentistry.

Goncheva said bacterial infections are most commonly acquired in hospital settings and hospitalization increases the risk of co-infection. “Bacterial infections are one of the most significant complications of respiratory viral infections such as COVID-19 and Influenza A. Despite the use of antibiotics, 25 per cent of patients co-infected with SARS-CoV-2 and bacteria, die as a result. This is especially true for patients who are hospitalized, and even more so for those in intensive care units. We were interested in finding why this happens,” said Goncheva, lead investigator of the study.

Goncheva, currently Canada Research Chair in virology and professor of biochemistry and microbiology at the University of Victoria, studied the pathogenesis of multi-drug resistant bacteria (such as MRSA) supervised by Heinrichs, professor of microbiology and immunology at Schulich Medicine & Dentistry.

When the COVID-19 pandemic hit, she pivoted to study interactions between MRSA and SARS-CoV-2.

For this study, conducted at Western’s level 3 biocontainment lab, Imaging Pathogens for Knowledge Translation (ImPaKT), Goncheva’s work created an out-of-organism laboratory model to study the interactions between SARS-CoV-2 and MRSA, a difficult-to-treat multi-drug resistant bacteria.

“At the beginning of the pandemic, the then newly opened ImPaKT facility made it possible for us to study the interactions between live SARS-CoV-2 virus and MRSA. We were able to get these insights into molecular-level interactions due to the technology at ImPaKT,” said Heinrichs, whose lab focuses on MRSA and finding drugs to treat MRSA infections. “The next step would be to replicate this study in relevant animal models.”

Source:

University of Western Ontario

Journal reference:

Goncheva, M. I., et al. (2023). The Staphylococcus aureus protein IsdA increases SARS CoV-2 replication by modulating JAK-STAT signaling. IScience. doi.org/10.1016/j.isci.2023.105975.

Microbiology

“Glow-in-the-Dark” Proteins: The Future of Viral Disease Detection?

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Although there have been significant advancements in diagnostic tests for viral diseases, many highly sensitive tests still rely on complex sample preparation and result interpretation methods, rendering them unsuitable for point-of-care settings or resource-limited areas. However, researchers have now revealed in ACS Central Science a novel, sensitive technique that can analyze viral nucleic acids in just 20 minutes using a one-step process with “glow-in-the-dark” proteins.

Bioluminescence, the scientific phenomenon behind the firefly’s glow, the anglerfish’s radiant lure, and the ghostly blue of phytoplankton-laden shores, is powered by a chemical reaction involving the luciferase protein. This luminescent protein has been integrated into sensors that emit visible light when detecting their target, making them ideal for straightforward point-of-care testing. However, until now, these sensors have not achieved the exceptional sensitivity necessary for clinical diagnostic tests.

The gene-editing technique known as CRISPR could provide this ability, but it requires many steps and additional specialized equipment to detect what can be a low signal in a complex, noisy sample. So, Maarten Merkx and colleagues wanted to use CRISPR-related proteins, but combine them with a bioluminescence technique whose signal could be detected with just a digital camera.

To make sure there was enough sample RNA or DNA to analyze, the researchers performed recombinase polymerase amplification (RPA), a simple method that works at a constant temperature of about 100 F. With the new technique, called LUNAS (luminescent nucleic acid sensor), two CRISPR/Cas9 proteins specific for different neighboring parts of a viral genome each have a distinct fragment of luciferase attached to them.

If a specific viral genome that the researchers were testing for was present, the two CRISPR/Cas9 proteins would bind to the targeted nucleic acid sequences and come close to each other, allowing the complete luciferase protein to form and shine blue light in the presence of a chemical substrate. To account for this substrate being used up, the researchers used a control reaction that shined green. A tube that changed from green to blue indicated a positive result.

When tested on clinical samples collected from nasal swabs, RPA-LUNAS successfully detected SARS-CoV-2 RNA within 20 minutes, even at concentrations as low as 200 copies per microliter. The researchers say that the LUNAS assay has great potential for detecting many other viruses effectively and easily.

Reference: “Glow-in-the-Dark Infectious Disease Diagnostics Using CRISPR-Cas9-Based Split Luciferase Complementation” by Harmen J. van der Veer, Eva A. van Aalen, Claire M. S. Michielsen, Eva T. L. Hanckmann, Jeroen Deckers, Marcel M. G. J. van Borren, Jacky Flipse, Anne J. M. Loonen, Joost P. H. Schoeber and Maarten Merkx, 15 March 2023, ACS Central Science.
DOI: 10.1021/acscentsci.2c01467

The study was funded by the Dutch Research Council | Nationaal Regieorgaan Praktijkgericht Onderzoek SIA (NRPO-SIA) and the Eindhoven University Fund.

American Chemical Society

Microbiology

New, Better Models Show How Infectious Diseases Like COVID-19 Spread

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The COVID-19 pandemic has emphasized the significance of modeling in comprehending the spread of diseases and in providing crucial insights into disease prevention and control. A new model has utilized COVID-19 data and combined two classic methodologies to enhance predictions about disease spread.

A widely used modeling technique involves dividing the population into compartments, such as susceptible (S), infected (I), and recovered (R), in what is known as the SIR model. This approach models the rates of change that describe the movement of individuals from one compartment to another.

KAUST researchers, led by Paula Moraga, integrated SIR compartment modeling in time and a point process modeling approach in space–time, while also taking into account age-specific contact patterns. To do this, they used a two-step framework that allowed them to model data on infectious locations over time for different age groups.

“The model gives more accurate predictions than previous approaches when making short/mid-range predictions in space and time,” says lead researcher André Amaral.

“It also accounts for different age classes so we can treat these groups separately, resulting in finer control over the number of infectious cases.”

Their approach paid off. In a simulation study to assess the model’s performance, and in a case study of COVID-19 cases in Cali, Colombia, the model performed better when making predictions and provided similar results for past time points, compared with models commonly used in predictive modeling.

“The model’s features can help decision-makers to identify high-risk locations and vulnerable populations to develop better strategies for disease control,” says Amaral.

It also can be used with any infectious disease that fits the compartment model assumptions, such as influenza. Furthermore, the model can account for different age groups and their associated contact patterns, meaning it allows more detailed conclusions about where, when, and to which population group decision-makers should focus their resources if they want to control disease spread.

“In future work, we might extend such an approach and use different temporal models to replace the SIR model. This would allow us to account for different epidemic dynamics and expand the number of scenarios that the model can be used for,” says Amaral.

“Finally, to improve the model’s predictive capabilities, we might work on developing ensemble approaches that combine a number of predictions from a number of different models and also account for potential time delays in collecting data,” he adds.

Moraga says the model’s performance demonstrates the importance of quality and detailed data by location, time, and population group to understand infectious disease dynamics while highlighting the need to strengthen national surveillance systems to improve public health decision-making.

Reference: “Spatio-temporal modeling of infectious diseases by integrating compartment and point process models” by André Victor Ribeiro Amaral, Jonatan A. González and Paula Moraga, 13 December 2022, Stochastic Environmental Research and Risk Assessment.
DOI: 10.1007/s00477-022-02354-4

King Abdullah University of Science & Technology (KAUST)

Microbiology

SARS-CoV-2 infection damages the CD8+ T cell response to vaccination

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Reviewed by Emily Henderson, B.Sc.Mar 20 2023

The magnitude and quality of a key immune cell’s response to vaccination with two doses of the Pfizer-BioNTech COVID-19 vaccine were considerably lower in people with prior SARS-CoV-2 infection compared to people without prior infection, a study has found. In addition, the level of this key immune cell that targets the SARS-CoV-2 spike protein was substantially lower in unvaccinated people with COVID-19 than in vaccinated people who had never been infected. Importantly, people who recover from SARS-CoV-2 infection and then get vaccinated are more protected than people who are unvaccinated. These findings, which suggest that the virus damages an important immune-cell response, were published today in the journal Immunity.

The study was co-funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and led by Mark M. Davis, Ph.D. Dr. Davis is the director of the Stanford Institute for Immunity, Transplantation and Infection and a professor of microbiology and immunology at Stanford University School of Medicine in Palo Alto, California. He is also a Howard Hughes Medical Institute Investigator.

Dr. Davis and colleagues designed a very sensitive tool to analyze how immune cells called CD4+ T cells and CD8+ T cells respond to SARS-CoV-2 infection and vaccination. These cells coordinate the immune system’s response to the virus and kill other cells that have been infected, helping prevent COVID-19. The tool was designed to identify T cells that target any of dozens of specific regions on the virus’s spike protein as well as some other viral regions. The Pfizer-BioNTech vaccine uses parts of the SARS-CoV-2 spike protein to elicit an immune response without causing infection.

The investigators studied CD4+ and CD8+ T-cell responses in blood samples from three groups of volunteers. One group had never been infected with SARS-CoV-2 and received two doses of the Pfizer-BioNTech COVID-19 vaccine. The second group had previously been infected with SARS-CoV-2 and received two doses of the vaccine. The third group had COVID-19 and was unvaccinated.

The researchers found that vaccination of people who had never been infected with SARS-CoV-2 induced robust CD4+ and CD8+ T-cell responses to the virus’ spike protein. In addition, these T cells produced multiple types of cell-signaling molecules called cytokines, which recruit other immune cells—including antibody-producing B cells—to fight pathogens. However, people who had been infected with SARS-CoV-2 prior to vaccination produced spike-specific CD8+ T cells at considerably lower levels—and with less functionality—than vaccinated people who had never been infected. Moreover, the researchers observed substantially lower levels of spike-specific CD8+ T cells in unvaccinated people with COVID-19 than in vaccinated people who had never been infected.

Taken together, the investigators write, these findings suggest that SARS-CoV-2 infection damages the CD8+ T cell response, an effect akin to that observed in earlier studies showing long-term damage to the immune system after infection with viruses such as hepatitis C or HIV. The new findings highlight the need to develop vaccination strategies to specifically boost antiviral CD8+ T cell responses in people previously infected with SARS-CoV-2, the researchers conclude.  

Source:

National Institutes of Health

Journal reference:

Gao, F., et al. (2023). Robust T cell responses to Pfizer/BioNTech vaccine compared to infection and evidence of attenuated peripheral CD8+ T cell responses due to COVID-19. Immunity. doi.org/10.1016/j.immuni.2023.03.005.

Microbiology

New SARS-CoV-2 Omicron XBB.1.5 variant has high transmissibility and infectivity, study finds

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Mar 20 2023Reviewed by Danielle Ellis, B.Sc.

COVID-19 has caused significant global panic after its rapid emergence more than 3 years ago. Although we now have highly effective vaccines against the SARS-CoV-2 virus, which causes COVID-19, scientists continue to study emerging SARS-CoV-2 variants in order to safeguard public health and devise global preventive strategies against emerging variants. A team led by Japanese researchers has recently discovered that the SARS-CoV-2 Omicron XBB.1.5 variant, prevalent in the Western hemisphere, has high transmissibility and infectivity.

New SARS-CoV-2 Omicron XBB.1.5 variant has high transmissibility and infectivity, study finds
New SARS-CoV-2 variant may jeopardize public health across the globe. The SARS-CoV-2 Omicron XBB.1.5 variant spreads rapidly and is more infectious than its historic precursor. Image Credit: The University of Tokyo

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for millions of deaths worldwide. Although scientists have designed novel vaccines to counter COVID-19, they are constantly on the lookout for emerging variants that can bypass vaccine resistance and potentially jeopardize global public health. A team led by Japanese researchers has recently been successful in characterizing the new SARS-CoV-2 Omicron XBB.1.5 variant, which was first detected in October 2022. Their findings were published on January 31, 2023 in volume 23 of The Lancet Infectious Diseases.​​​

Says senior author Prof. Kei Sato from the Division of Systems Virology, The Institute of Medical Science, The University of Tokyo, Japan, “Because the Omicron XBB.1.5 variant can spread more rapidly than previous variants and has a potential to cause the next epidemic surge, we should carefully monitor it to safeguard public health.”

While studying emerging variants of the SARs-CoV-2 Omicron lineage, the research team made a startling discovery: the SARS-CoV-2 Omicron XBB.1.5 variant has a novel mutation in the spike (S) protein—the protein that anchors the virus firmly to the human angiotensin converting enzyme-2 (ACE2) receptor, thus facilitating the invasion of human cells. The serine-to-proline amino acid mutation noted at residue no. 486 in the S protein is virologically concerning because of a variety of reasons.

Sharing his concerns, first author Keiya Uriu from the Division of Systems Virology, Department of Microbiology and Immunology, The University of Tokyo, Japan, says, “In late 2022, the SARS-CoV-2 Omicron BQ.1 and XBB lineages, characterized by amino acid substitutions in the S protein and increased viral fitness, had become predominant in the Western and Eastern Hemisphere, respectively. In 2022, we elucidated the characteristics of a variety of newly emerging SARS-CoV-2 Omicron subvariants. At the end of 2022, the XBB.1.5 variant, a descendant of XBB.1 that acquired the S:S486P substitution, emerged and was rapidly spreading in the USA.”

To gain mechanistic insights into the infectivity, transmissibility, and immune response associated with XBB.1.5, the team conducted a series of experiments. For instance, upon conducting epidemic dynamics analysis—statistical modeling that facilitates the analysis of the general characteristics of any epidemic—the team realized that the relative effective reproduction number (Re) of XBB.1.5 was 1.2-fold greater than that of the parental XBB.1. This indicated that an individual with the XBB.1.5 variant could infect 1.2 times more people in the population than someone with the parental XBB.1 variant. Moreover, the team also realized that, as of December 2022, XBB.1.5 was rapidly outcompeting BQ.1.1, the predominant lineage in the United States.

Co-first-author Jumpei Ito from the Division of Systems Virology, remarks, “Our data suggest that XBB.1.5 will rapidly spread worldwide in the near future.”

The team also studied the virological features of XBB.1.5 to determine how tightly the S protein of the new variant interacts with the human ACE2 receptor. To this end, the researchers conducted a yeast surface display assay. The results showed that the dissociation constant (KD) corresponding to the physical interaction between the XBB.1.5 S receptor-binding domain (RBD) and the human ACE2 receptor is significantly (4.3-fold) lower than that for XBB.1 S RBD. “In other words, the XBB.1.5 variant binds to human ACE2 receptor with very high affinity,” explains Shigeru Fujita from the Division of Systems Virology.

Further experiments using lentivirus-based pseudoviruses also showed that XBB.1.5 had approximately 3-fold higher infectivity than XBB.1. These results suggest that XBB.1.5 exhibits a remarkably strong affinity to the human ACE2 receptor, which can be attributed to the S486P substitution.

The study by Prof. Sato and his team led to another important discovery from an immunization perspective. The XBB.1.5 S protein was found to be highly resistant to neutralization antibodies elicited by breakthrough infection with the BA.2/BA.5 subvariants. In other words, patients with prior infection from the BA.2/BA.5 subvariants may not show robust immunity against XBB.1.5, increasing their chances of infection and disease.

The results of our virological experiments explain why the Omicron XBB.1.5 variant has a higher transmissibility than past variants: This variant acquired strong binding ability to human ACE2 while maintaining a higher ability to escape from neutralizing antibodies.”

​​​​​​​Yusuke Kosugi, Division of Systems Virology, Department of Microbiology and Immunology, The University of Tokyo, Japan

Contributing members of The Genotype to Phenotype Japan (G2P-Japan) Consortium conclude, “The SARS-CoV-2 Omicron XBB.1.5 variant does show enhanced transmissibility. Although few cases have been detected in the Eastern hemisphere, it could become a looming threat. Imminent prevention measures are needed.”

​​​​​​​Thanks to the research team for the early warning! Meanwhile, we must continue adopting safe practices to defend ourselves from XBB.1.5. 

Source:

The University of Tokyo

Journal reference:

Uriu, K., et al. (2023) Enhanced transmissibility, infectivity, and immune resistance of the SARS-CoV-2 omicron XBB.1.5 variant. The Lancet Infectious Diseases. doi.org/10.1016/S1473-3099(23)00051-8.

Microbiology

UFO Sightings and COVID-19 Pandemic Link Tested in Surprising New Research

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Have you ever wondered if social factors like pandemics can affect UFO reporting? In a recent article published in the Journal of Scientific Exploration, authors Chase Cockrell from the University of Vermont, and Mark Rodeghier and Linda Murphy from the Center for UFO Studies, investigated whether the COVID-19 pandemic was associated with an increase in UFO sightings.

The authors hypothesized that the COVID-19 pandemic, which resulted in lockdowns and social distancing measures, may have led to an increase in UFO sightings. The reasoning behind this hypothesis was that with more people staying home and spending time outdoors, there may have been an increase in available free time, which could result in more UFO sightings. Additionally, the authors tested the idea that increased feelings of anxiety and uncertainty may have led to heightened attention to the environment, which could have caused people to more often notice unusual phenomena and make sense of what they experienced by connecting it with UFOs.

The authors analyzed data from the National UFO Reporting Center (NUFORC) and the Mutual UFO Network (MUFON), the two most comprehensive UFO reporting sites in the United States, from 2018 through 2020 and compared the number of UFO reports before and after the start of the pandemic.  To test whether social factors could have influenced the number of reports, they used publicly available data for social mobility from Google Community Mobility Reports, and SARS-CoV-2 cases and deaths, which are indirect measures of stress and anxiety.

Their analysis demonstrated that UFO reports did increase in 2020 compared to the previous year by about 600 reports in each database. However, there was no association between the number of reports—aggregated across the US or by state—with the mobility and pandemic health measures, providing no support that social factors led to increased reports.

The researchers then searched for alternative causes and identified the initiation of regular launches of Starlink satellites beginning in late 2019 as a complicating factor. These launches include up to 60 small satellites at once, which are very distinctive and often easily visible. As a result, many people understandably reported these as UFOs. The analysis demonstrated a relationship between a launch and subsequent reports. After removing these reports, they retested the association with the social and pandemic-health factors, but again found no relationship. Critically, with the Starlink reports removed, there was no statistical increase in reports in 2020, and even a decrease in reports to NUFORC.

The astronomical community is concerned about the impact of Starlink, and other similar projects, launching large numbers of satellites in relatively low orbits and potentially degrading astronomical measurements. The authors demonstrated that the UFO community has a similar problem.

“This study sheds light on the potential impact of social factors on UFO reporting,” says Mark Rodeghier, Scientific Director of the Center for UFO Studies. While they found that the COVID-19 pandemic did not significantly impact UFO reporting, their findings suggest that future research should investigate other factors that may influence reporting.

Reference: “Social factors and UFO reports: Was the SARS-CoV-2 pandemic associated with an increase in UFO reporting?” by R Chase Cockrell, Linda Murphy and Mark Rodeghier, 11 February 2023, Journal of Scientific Exploration.
DOI: 10.31275/20222681

Society for Scientific Exploration

Microbiology, News

ASM Statement in Response to COVID-19 Hearing

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ASM Statement in Response to COVID-19 Hearing

Statement from the American Society for Microbiology 
in response to the 
House Select Subcommittee on the Coronavirus Pandemic Hearing: 
“Investigating the Origins of COVID-19” 
 
March 8, 2023 

On behalf of our 30,000 members in the United States and around the world, the American Society for Microbiology (ASM) shares the following points in response to the House Select Subcommittee on the Coronavirus Pandemic’s hearing to discuss the origins of COVID-19, the disease caused by the SARS-CoV-2 virus.     

ASM supports a science-based, open and comprehensive inquiry into the origins of the pandemic. We are encouraged that government and intelligence agencies continue their due diligence in the investigation.  The conclusions we draw about the origins of COVID-19 will inform the future of high-consequence pathogen research around the world and pandemic preparedness here in the U.S., so it is crucial that we conduct a free, open and complete inquiry and do not draw premature conclusions. Because pathogens know no borders, we also urge international collaboration, to the extent possible, in the search for evidence and answers. 

Novel pathogens with the ability to infect humans have emerged at an increasing rate over the past twenty years. Many threaten global health, but none more so in recent memory than SARS-CoV-2. In addition to novel pathogens, we must address seasonal threats with pandemic potential such as influenza, and recurring epidemic threats such as Ebola. Whenever such threats emerge, questions arise as to how the event happened. Understanding how an epidemic or pandemic starts helps us better prepare for future pandemics. It is essential to lead with science in order to achieve the most complete and accurate understanding of how infectious diseases emerge and spread.  

As such, we offer the following points for consideration: 

  • The United States is the world leader in life sciences research, including basic, clinical and translational research focused on pathogens and infectious diseases. Congress must continue to support the U.S. research ecosystem through a strong federal funding commitment, coupled with policies that enable innovative public private partnerships. By doing so, we can continue promising research to understand how viruses emerge and are transmitted; how they can be prevented, detected, and monitored; and, when they cause disease, how they can be diagnosed and treated. Without continued research in these areas, we will not be able to prevent or even prepare for future pandemics.

 

  • When this work involves working with enhanced potential pandemic pathogens (ePPPs), it must be accompanied by safeguards and conducted under strict biosafety and biosecurity measures in laboratories at the appropriate biocontainment safety level (BSL).  The American public can have confidence that research conducted on ePPPs in the U.S. adheres to the highest standards that set the bar for countries around the world. We have an impeccable track record in this country and recognize the need to continually refine and update standards. But for this leadership to continue, Congress must invest in the network of high containment laboratories to ensure that the infrastructure is sound, laboratorians are appropriately trained, and the work is conducted with minimal risk to both those working in the lab and to the general population.

 

  • Research on disease-causing microbes is necessarily international. As we have seen all too clearly, viruses know no borders. Many of the viruses emerge at the animal-human interface outside of the U.S., so the health and security of the American public depends on transparent research collaborations and sharing of samples and genomic sequencing information with other countries. Work outside the U.S. needs to occur at a biosafety level comparable to that which is applied domestically to reduce risk of lab accidents. With diplomacy and American leadership, ASM believes it is possible to both protect national security and work with governments and researchers in other countries to ensure that this work is being conducted safely. We all want the work to protect people throughout the world, and we need the information to anticipate and detect threats. 

We thank the Subcommittee for consideration of our views. ASM is committed to assisting the Committee, its members, the Congress, and the Administration as the U.S. continues to recover from and consider lessons learned from the COVID-19 pandemic.  

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The American Society for Microbiology is one of the largest professional societies dedicated to the life sciences and is composed of 30,000 scientists and health practitioners. ASM’s mission is to promote and advance the microbial sciences.  

ASM advances the microbial sciences through conferences, publications, certifications and educational opportunities. It enhances laboratory capacity around the globe through training and resources. It provides a network for scientists in academia, industry and clinical settings. Additionally, ASM promotes a deeper understanding of the microbial sciences to diverse audiences.