Previous infection with coronavirus does not necessarily protect against Covid in the longer term, especially when caused by new variants of concern, a study on healthcare workers suggests.
Researchers at Oxford University found marked differences in the immune responses of medical staff who contracted Covid, with some appearing far better equipped than others to combat the disease six months later.
Scientists on the study, conducted with the UK Coronavirus Immunology Consortium, said the findings reinforced the importance of everyone getting vaccinated regardless of whether they had been infected with the virus earlier in the pandemic.
“If you look at the trajectory of the immune response after infection, mostly it is still detectable six months later, but it’s highly variable between people,” said Eleanor Barnes, a professor of hepatology and experimental medicine at Oxford and a senior author on the study.
“That is quite different to vaccination. If you vaccinate you get a really robust response, but with natural infection there’s much more diversity in responses.”
The researchers analysed blood samples from 78 healthcare workers who had Covid, with or without symptoms, between April and June last year. The blood was checked monthly for up to six months post-infection for a range of immune responses. These included different types of antibody that target the virus, B cells that make antibodies and retain a memory of the disease, and T cells, which reduce the severity of disease by killing off infected cells.
Writing in a preprint, which has yet to be peer-reviewed, the authors describe how they used a machine learning system called Simon, for Sequential Iterative Modeling Over Night, to see whether a person’s early immune response and the severity of their infection could predict their longer-term immunity. Dr Adriana Tomic, the first author on the study, said a signature in the antibody and T-cell response at one month predicted how robust the antibody response would be at six months.
The majority of people who produced a weak immune response at one month had no detectable antibodies that could neutralise the Alpha variant, first seen in Kent, at six months. None mounted neutralising antibodies against the Beta variant first spotted in South Africa. The researchers have yet to analyse data for the Delta variant now dominant in the UK.
While most of the healthcare workers who developed symptomatic disease had a measurable immune response six months later, more than a quarter did not. More than 90% of those who had asymptomatic infections had no measurable immune response six months later, the researchers found. The work is part of the protective immunity from T cells to Covid-19 in health workers (Pitch) study, funded by the Department of Health.
“In our view, previous infection does not necessarily protect you long-term from Sars-Cov-2, particularly variants of concern,” said Barnes. “You shouldn’t depend on it to protect you from subsequent disease, you should be vaccinated.”
The wide variability in immunity triggered by natural infection in part reflects the radically different exposures people can have to the virus while going about their lives. Immunity from vaccination is more reliable because people are given a standard dose in a standard way.
Danny Altmann, a professor of immunology at Imperial College London, who was not involved in the study, said the findings cautioned against simple assumptions around how immunity waned with time. “People show rather diverse trajectories after infection, but immunity often seems to hold up well at six months,” he said. “Most of all, studies such as this remind us that policy decisions on ‘boosting’ need to be evidence based in the context of a strong programme of immune monitoring.”
New Delhi: Immunity in Covid-recovered patients is long-lasting and gets a 50-fold boost after vaccination, according to a new study.
The study, published in the journal Nature Monday, also said that the mRNA vaccines can sufficiently protect against emerging mutations.
More than a year after the Covid-19 pandemic broke, the emergence of new variants that appear to be more transmissible and resistant to antibodies has added to the challenge of controlling the spread of the disease.
To understand how long the immunity lasts, researchers from the Rockefeller University, Weill Cornell Medicine and California Institute of Technology assessed the blood samples of 63 people who had recovered from Covid-19. The samples were collected 1.3, 6.2 and 12 months after infection.
Of these 63 people, 41 per cent had received mRNA vaccines.
The study found that in Covid-recovered patients, antibodies against the protein known as receptor binding domain (RBD) of SARS-CoV-2 and neutralising activity remain relatively stable from six to 12 months, without vaccination.
A receptor-binding domain is a key part of the virus located on its ‘spike’ protein that allows it to latch onto the cell to gain entry into cells and lead to infection.
Memory B cells — a type of white blood cells that learn to recognise specific viral proteins — was also found to remain stable upto 12 months.
In addition, the team found that vaccination increases all components of the antibody response. Antibody levels remained relatively unchanged between six to 12 months after SARS-CoV-2 infection, and that vaccination further boosted this activity by nearly 50-fold.
The study found that the ability of vaccine-induced antibodies to neutralise variants of concern was comparable to or greater than that against the original virus.
Researchers also identified that the broad response against the SARS-CoV-2 virus involves what is known as the antibody somatic mutation — a cellular mechanism using which the body’s immune system adapts to the changing virus during the course of the infection.
This results in antibodies that are exceptionally resistant to mutations in the SARS-CoV-2 RBD — including those found in variants of concern
In addition, B cells that produce a broad range of potent antibodies are retained in the body over time and expand dramatically after vaccination.
The data suggest that immunity in Covid-recovered individuals will be very long-lasting, researchers said. Along with this, Covid-recovered patients who receive mRNA vaccines produce antibodies and memory B cells that should be protective against circulating SARS-CoV-2 variants, the study concluded.
India needs free, fair, non-hyphenated and questioning journalism even more as it faces multiple crises.
But the news media is in a crisis of its own. There have been brutal layoffs and pay-cuts. The best of journalism is shrinking, yielding to crude prime-time spectacle.
ThePrint has the finest young reporters, columnists and editors working for it. Sustaining journalism of this quality needs smart and thinking people like you to pay for it. Whether you live in India or overseas, you can do it here.
Fungal diseases in cereal crops cause major economic losses and also threaten human and livestock health, because some fungi produce powerful toxins that might enter the food chain. Farmers use fungicides to control crop diseases, such as wheat head blight. Although agrochemicals are rigorously tested for safety, there can be concerns over chemical residues in food.
Now, researchers at Kanazawa University, in collaboration with colleagues at Ehime University and Nagoya University, have shown that the natural substance nicotinamide (NIM – a vitamin found in food and used as a dietary supplement) can help stimulate plant immune systems.
Pre-treatment with NIM can prevent or reduce development of fungal disease in wheat plants. This knowledge could lead to new approaches to tackle crop diseases. The team recently published their work in the International Journal of Molecular Sciences.
When the team pre-treated with NIM the spikes of wheat plants (carrying the young grains that are later harvested to make flour) and then inoculated the plants with conidia of Fusarium graminearum (which causes head blight), the NIM pre-treatment strongly suppressed the disease. Pre-treated plants contain much less fungal biomass, and less of a mycotoxin it produces, compared with water-treated plants.
The team also performed metabolomics to analyze the contents of hundreds of compounds in the plants and found that NIM pre-treatment increased the amounts of 375 substances. Among those markedly increased were several antimicrobial and antioxidant compounds.
We found that pre-treating wheat plants with NIM led to the activation of plant immune response and much higher content of the plant’s own defense-related compounds, including antimicrobial substances. This work builds on previous research using other natural chemicals related to NIM and has the added advantages of being relatively cheap, readily available, and stable at room temperature.”
Yasir Sidiq, Study Lead Author, Kanazawa University
This work represents a significant step forward in developing environmentally friendly ways to tackle important diseases in crops. “We expect our study will lead to novel approaches in agriculture,” corresponding author Takumi Nishiuchi explains, “potentially replacing toxic fungicide sprays with new ways of stimulating the plant innate immune responses – similar to how vaccinating humans or animals primes their immune systems against later infection.”
Sidiq, Y., et al. (2021) Nicotinamide Effectively Suppresses Fusarium Head Blight in Wheat Plants. International Journal of Molecular Sciences. doi.org/10.3390/ijms22062968.
Since the Apollo missions started almost 60 years ago, scientists have been monitoring space travel’s negative effects on health.
A new study concludes that reduced gravity makes the immune system malfunction, reducing the immune response.
This study could pave the way for developing methods that reduce immune system impairment during long-term space exploration.
Dr. Millie Hughes-Fulford was one of the first female astronauts. Until her death in February 2021, she led a team of researchers at University of California, San Francisco (UCSF) and Stanford University in investigating the role of regulatory T cells (Tregs) in immune system dysfunction during space travel.
The lead author of the new study is Dr. Jordan Spatz, a postdoctoral fellow and space scientist at UCSF, and the senior author is Dr. Brice Gaudilliere, an associate professor in the Department of Anesthesia at the Stanford University School of Medicine.
These findings inspired probes into the effects of microgravity on the immune system.
Over the past 6 decades, scientists have led such inquiries during rocket launches, shuttle trips, space station terms, and earthbound laboratory space gravity simulations.
Tregs play a vital role in regulating many types of immune responses. Often, these cells dampen the immune responses as an infection subsides.
They are involved in a number of processes, including oral tolerance, which is “the active process by which the immune system does not respond to an orally administered antigen,” such as food. Tregs also play a role in resistance to infections, allergy sensitivities, immune memory, and transplantation tolerance, in which the immune system does not attack transplanted tissue.
The current study’s findings indicate that space travel activates Tregs earlier, thereby damping down the immune system before the threat has been cleared.
The scientists exposed blood samples from eight healthy adult participants to simulated microgravity.
They loaded the samples into a machine developed by the National Aeronautics and Space Administration (NASA), called the Rotating Wall Vessel, exposing the samples to 18 hours of either 1-gravity, which is the amount of gravity experienced on Earth, or microgravity.
Using a novel single-cell analysis, the researchers could pinpoint individual immune cells by type in order to detect and tally proteins involved in immune function.
This study offers greater insight into the cellular interactions that explain microgravity’s immunosuppressive effects.
According to the researchers, the lack of gravity seems to set off a multicellular response that may lower resistance to pathogens.
Surprisingly, when the team stimulated an immune response in the blood samples with two molecules that mimicked a pathogen, the Tregs dampened the resulting immune response before it had time to respond to the threat.
The study authors report: “Our data indicate that exposure to [microgravity] results in the broad inhibition of immune cell capacity to respond to a potent activating stimulus […] and are consistent with transcriptomic previous analyses of human immune cells exposed to the spaceflight environment.”
Dr. Gaudilliere calls this a “double whammy” of “a dampening of T lymphocyte immune activation responses — but also an exacerbation of immunosuppressive responses by Tregs.” T lymphocytes, which are also called T cells, play a central role in the body’s response to pathogens. Under microgravity, T cells are less responsive. However, antibody-producing B cells were not affected in the same way.
The study’s authors mention several limitations. They stress that using a microgravity simulation model makes it hard to generalize the findings. However, they argue that this cost-effective experimentation can identify novel biological effects that can later be tested in-flight.
Also, the study’s design concentrated on one time point of exposure to low gravity. The team feels that future investigations with additional time points “are warranted and should be high priority.”
In addition, the short-term incubation time did not provide enough opportunity to measure differences in cell proliferation.
The evaluation also noted the immune response to a single stimulus, limiting the analysis of the functional response of immune cells to other stimuli or pathogens.
Reduced immune response, accelerated pathogen activity, and heightened viral shedding in astronauts in space pose significant risks for both short- and long-term space travel.
Dr. Spatz expresses concern about the growing public demand for space travel, as well:
“Early in the space program, most astronauts were young and extremely healthy, but now they tend to have much more training and are older. In addition, […] with the commercialization of spaceflight, there will be many older and less healthy individuals experiencing microgravity.”
The lead and senior study authors believe that their team’s work can aid in developing interventions to reduce the consequences of suppressed immunity during spaceflight.
A new study looking at the way human cells activate the immune system in response to COVID-19 infection could open the door to even more effective and powerful vaccines against SARS-CoV-2 and the rapidly emerging variants keeping the global coronavirus pandemic smoldering.
Researchers from Boston University’s National Emerging Infectious Diseases Laboratories (NEIDL) and the Broad Institute of MIT and Harvard say it’s the first real look at exactly what types of “red flags” the human body uses to enlist the help of T cells—killers sent out by the immune system to destroy infected cells. Until now, COVID vaccines have been focused on activating a different type of immune cell, B cells, which are responsible for creating antibodies. Developing vaccines to activate the other arm of the immune system—the T cells—could dramatically increase immunity against coronavirus, and importantly, its variants.
In their findings, published in Cell, the researchers say current vaccines might lack some important bits of viral material capable of triggering a holistic immune response in the human body. Based on the new information, “companies should reevaluate their vaccine designs,” says Mohsan Saeed, a NEIDL virologist and the co-corresponding author of the paper.
Saeed, a BU School of Medicine assistant professor of biochemistry, performed experiments on human cells infected with coronavirus. He isolated and identified those missing pieces of SARS-CoV-2 proteins inside one of the NEIDL’s Biosafety Level 3 (BSL-3) labs. “This was a big undertaking because many research techniques are difficult to adapt for high containment levels [such as BSL-3],” Saeed says. “The overall coronavirus research pipeline we’ve created at the NEIDL, and the support of our entire NEIDL team, has helped us along the way.”
Saeed got involved after he was contacted by genetic sequencing experts at the Broad Institute, computational geneticists Pardis Sabeti and Shira Weingarten-Gabbay. They hoped to identify fragments of SARS-CoV-2 that activate the immune system’s T cells.
“The emergence of viral variants, an active area of research in my lab, is a major concern for vaccine development,” says Sabeti, a leader in the Broad Institute’s Infectious Disease and Microbiome Program. She is also a Harvard University professor of systems biology, organismic and evolutionary biology, and immunology and infectious disease, as well as a Howard Hughes Medical Institute investigator.
“We swung into full action right away because my laboratory had [already] generated human cell lines that could be readily infected with SARS-CoV-2,” Saeed says. The group’s efforts were spearheaded by two members of the Saeed lab: Da-Yuan Chen, a postdoctoral associate, and Hasahn Conway, a lab technician.
From the outset of COVID pandemic in early 2020, scientists around the world knew the identity of 29 proteins produced by SARS-CoV-2 virus in infected cells—viral fragments that now make up the spike protein in some coronavirus vaccines, such as Johnson & Johnson’s. Later, scientists discovered another 23 proteins hidden inside the virus’ genetic sequence; however, the function of these additional proteins was a mystery until now. The new findings of Saeed and his collaborators reveal—unexpectedly and critically—that 25 percent of the viral protein fragments that trigger the human immune system to attack a virus come from these hidden viral proteins.
How exactly does the immune system detect these fragments? Human cells contain molecular “scissors”—called proteases—that, when the cells are invaded, hack off bits of viral proteins produced during infection. Those bits, containing internal proteins exposed by the chopping-up process—like the way the core of an apple is exposed when the fruit is segmented—are then transported to the cell membrane and pushed through special doorways. There, they stick outside the cell acting almost like a hitchhiker, waving down the help of passing T cells. Once T cells notice these viral flags poking through infected cells, they launch an attack and try to eliminate those cells from the body. And this T cell response isn’t insignificant—Saeed says there are links between the strength of this response and whether or not people infected with coronavirus go on to develop serious disease.
“It’s quite remarkable that such a strong immune signature of the virus is coming from regions [of the virus’ genetic sequence] that we were blind to,” due to the fact that many researchers around the world were so focused on the coronavirus’ spike protein, but not the rest of the virus’ genetic code, says Weingarten-Gabby, the paper’s lead author and postdoctoral fellow in the Sabeti lab. “This is a striking reminder that curiosity-driven research stands at the basis of discoveries that can transform the development of vaccines and therapies.”
“Our discovery … can assist in the development of new vaccines that will mimic more accurately the response of our immune system to the virus,” Sabeti says.
T cells not only destroy infected cells but also memorize the virus’ flags so that they can launch an attack, stronger and faster, the next time the same or a different variant of the virus appears. That’s a crucial advantage, because Saeed and his collaborators say the coronavirus appears to delay the cell’s ability to call in immune help.
“This virus wants to go undetected by the immune system for as long as possible,” Saeed says. “Once it’s noticed by the immune system, it’s going to be eliminated, and it doesn’t want that.”
Based on their findings, Saeed says, a new vaccine recipe, incorporating some of the newly discovered internal proteins making up the SARS-CoV-2 virus, would be effective in stimulating an immune response capable of tackling a wide swath of newly emerging coronavirus variants. And given the speed with which these variants continue to appear around the world, a vaccine that can provide protection against all of them would be a game changer.
LOS ANGELES (CNS) – Results of a new study released today by UCLA suggests that a class of drug commonly prescribed to treat depression might have another health benefit by helping the immune system attack cancer.
The class of drug called monoamine oxidase inhibitors work by boosting levels of serotonin, the brain’s “happiness hormone,” according to researchers.
“MAOIs had not been linked to the immune system’s response to cancer before,” said Lili Yang, senior author of the study and a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.
“What’s especially exciting is that this is a very well-studied and safe class of drug, so repurposing it for cancer isn’t as challenging as developing a completely new drug would be.”
The findings are reported in two papers, which are published in the journals Science Immunology and Nature Communications.
Recent advances in understanding how the human immune system naturally seeks out and destroys cancer cells, as well as how tumors try to evade that response, has led to new cancer immunotherapies — drugs that boost the immune system’s activity to try to fight cancer.
In an effort to develop new cancer immunotherapies, Yang and her colleagues compared immune cells from melanoma tumors in mice to immune cells from cancer-free animals. Immune cells that had infiltrated tumors had much higher activity of a gene called monoamine oxidase A, or MAOA. MAOA’s corresponding protein, called MAO-A, controls levels of serotonin and is targeted by MAOI drugs.
“For a long time, people have theorized about the cross-talk between the nervous system and the immune system and the similarities between the two,” said Yang, who is also a UCLA associate professor of microbiology, immunology and molecular genetics and a member of the UCLA Jonsson Comprehensive Cancer Center.
“So it was exciting to find that MAOA was so active in these tumor-infiltrating immune cells.”
Newswise — JUNE 10, 2021, NEW YORK – A Ludwig Cancer Research study adds to growing evidence that immune cells known as macrophages inhabiting the body cavities that house our vital organs can aid tumor growth by distracting the immune system’s cancer-killing CD8+ T cells.
Reported in the current issue of Cancer Cell and led by Ludwig investigators Taha Merghoub and Jedd Wolchok at Memorial Sloan Kettering (MSK) and Charles Rudin of MSK, the study shows that cavity-resident macrophages express high levels of Tim-4, a receptor for phosphatidylserine (PS), a molecule that they surprisingly found on the surface of highly activated, cytotoxic and proliferative CD8+ T-cells.
“We believe T-cells that infiltrate the peritoneal cavity can be distracted by the interaction with Tim-4-expressing macrophages,” explained study first author Andrew Chow, an assistant attending physician at the Ludwig Collaborative Laboratory at MSK.
The researchers also show that blocking Tim-4 in mouse models of cancer can prevent this distractive interaction and enhance the effectiveness of immunotherapies.
“I think in patients who have these serous cavity macrophages expressing high levels of Tim-4, blocking Tim-4 will make immune based therapies more effective,” Merghoub, co-director of the Ludwig Collaborative Laboratory at MSK, said.
Just as people living in different cities might have distinct customs or accents, the macrophages in our bodies can adopt specialized functions and respond to disease differently depending on which tissue they inhabit. Scientists are increasingly interested in such localized responses because macrophage activities can influence recovery from illness or injury and responses to therapy.
Merghoub, Wolchok, Rudin, Chow and colleagues began exploring the role of macrophages in tumor immunosuppression after noticing that cancer patients with lesions in their pleural and peritoneal cavities—which house the lungs and organs of the gastrointestinal tract, respectively—were substantially less responsive to immune checkpoint blockade therapy, which stimulates a CD8+ T cell attack on tumors.
“That told us there was something immunosuppressive in these cavities, so we went hunting for what that could be,” Chow said.
Previous studies have shown that other immunosuppressed sites in the body, such as the liver and bone, harbor macrophages expressing high levels of Tim-4. Others have shown that macrophages living in the pleural and peritoneal cavities of mice also exhibit a strong Tim-4 signal.
The researchers therefore suspected that cavity-resident macrophages might impair the anti-tumor activity of CD8+ T cells through the actions of Tim-4.
These suspicions were partly vindicated when the researchers analyzed the cavity macrophages of human lung cancer patients and found that while Tim-4 levels varied between individuals, those with higher levels of the receptor tended to have a reduced presence of CD8+ T cells that had features of responding to the tumor.
Based on these observations, the researchers explored whether blocking Tim-4 would enhance the efficacy of PD-1 blockade therapies in a pre-clinical mouse model of colon and lung cancer in the peritoneal cavity.
“We showed that you get the best tumor protection when you block both molecules,” Chow said.
While blocking Tim-4 alone didn’t reduce the number of tumors or improve survival in the mice, it did enhance the tumor protection afforded by PD-1 blockade and boost the numbers of CD8+ T cells in the peritoneal cavity. The researchers also showed that Tim-4 blockade reduces immunosuppression in adoptive T-cell therapy, in which tumor-targeting T-cells are isolated and selectively grown in a lab before they’re reinfused into the patient.
“Together, these results suggest that Tim-4 blockade is a strategy to improve immunotherapy, regardless of whether you’re trying to boost your immune response through immune checkpoint blockade therapy or via adoptive T-cell therapy,” said Chow.
For Merghoub, the new findings demonstrate the need to better understand the diversity of immune landscapes in and around tumors. “In the same way we profile tumor genomes to guide the use of small molecule inhibitors for targeted therapies, we need to profile the immune landscapes of tumors and personalize immune-based therapies on the basis of such studies,” he said.
Taha Merghoub is co-director of the Ludwig Collaborative & Swim Across America Laboratory at MSK and professor of immunology research in medicine at Weill Cornell Medical College.
Jedd Wolchok is associate director of the Ludwig Center and director of the Ludwig Collaborative & Swim Across America Laboratory, chief of the immuno-oncology service, the Lloyd J. Old/Virginia and Daniel K. Ludwig Chair in Clinical Investigation and director of the Parker Institute for Cancer Immunotherapy at MSK.
This study was supported by Ludwig Cancer Research, Swim Across America, Parker Institute for Cancer Immunotherapy, The Emerald Foundation, the US National Cancer Institute, MSKCC, the American Cancer Society, the International Association for the Study of Lung Cancer and the US Department of Defense.
# # #
About Ludwig Cancer Research
Ludwig Cancer Research is an international collaborative network of acclaimed scientists that has pioneered cancer research and landmark discovery for 50 years. Ludwig combines basic science with the ability to translate its discoveries and conduct clinical trials to accelerate the development of new cancer diagnostics and therapies. Since 1971, Ludwig has invested nearly $3 billion in life-changing science through the not-for-profit Ludwig Institute for Cancer Research and the six U.S.-based Ludwig Centers. To learn more, visit www.ludwigcancerresearch.org.
The University of Rochester Medical Center (URMC) is participating in a new clinical trial that will mix-and-match the initial regime of an approved vaccine with a booster dose from a different manufacturer. The research will help inform public health decisions around re-vaccination schedules and the deployment of boosters that target COVID variants.
“As the number of Americans receiving a vaccine continues to rise, we now need to think about the long-term strategy to combat coronavirus,” said Ann Falsey, professor of Medicine, Infectious Diseases at URMC. “This effort will probably look like vaccination programs for other infectious diseases, like the flu. This study is a critical step and will show if doses from different vaccines are safe, tolerable, and sufficiently boost the immune system enough to fight off reinfection by SAR-CoV-2 and variants.”
Falsey and Angela Branche, M.D., are co-directors of the URMC Vaccine and Treatment Evaluation Unit (VTEU), part of a network of National Institute of Allergy and Infectious Diseases (NIAID)-funded research sites that have led the scientific response to the coronavirus pandemic. Falsey, Branche, and David Dobrzynski, M.D., an assistant professor of Medicine, Infectious Diseases at URMC, are leading the Rochester site of the study.
Coronavirus continues to circulate at high rates globally and scientists speculate that COVID could evolve to become a seasonal, mutating virus that remains with us for years to come. While researchers have speculated that the immune system could provide protection that lasts years, it remains unknown how long the immunity from vaccines will last. As is the case with other vaccines, it is assumed that over time the immune response to COVID will weaken, necessitating a booster dose to keep the immune system primed to fight off infection.
The emergence of variants is another complication that will dictate future coronavirus booster dose strategies. As of now, the Pfizer-BioNTech and Moderna vaccines appear to be very effective against most of the identified variants of COVID, including the Indian variant that is spreading across South Asia. However, it is possible that variants could emerge that render existing vaccines less effective or potentially even evade the protection provided by vaccines altogether, necessitating new versions of the vaccine.
The optimization and distribution COVID vaccines is of critical public health priority. The National Institutes of Health, Centers for Disease Control and Prevention, and World Health Organization have prioritize the study of “mixed schedules” to determine whether immunity is sufficiently strengthened if someone gets their original vaccine and a booster dose from different manufacturers. If shown effective, the findings from this study could help resolve some of the distribution challenges that often beset large-scale vaccination programs by removing dependency on a single company for national and global vaccine supply.
The new phase 1/2 clinical trial, which is being funded by NIAID, will recruit two groups of volunteers:
Individuals 18 years or older who have not yet been vaccinated; and
Individuals 18 years or older who have completed their initial vaccination within the last 12-20 weeks.
Unvaccinated participants will receive the Moderna vaccine and then a booster dose of either the same vaccine or a Moderna variant vaccine 12 weeks later. Volunteers who have already been vaccinated with the either the Moderna, Pfizer-BioNTech, or Johnson & Johnson vaccines will receive a booster dose of the Moderna vaccine. The study seeks to enroll 500 participants in the U.S., including approximately 50 local volunteers.
“One of the key scientific question we are trying to answer is whether vaccines that use different platforms—such as mRNA, adenovirus, and protein-based—can sufficiently strengthen the original immune response generated by a different vaccine technology,” said Branche. “If we can show that the immune response to COVID and variants can been prolonged by booster doses, regardless of the manufacturer, then that will inform vaccination plans in future years.”
New study mixes vaccine doses to boost immunity to COVID and variants (2021, June 9)
retrieved 9 June 2021
This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no
part may be reproduced without the written permission. The content is provided for information purposes only.
The University of Rochester Medical Center (URMC) is participating in a new clinical trial that combines the initial prescription of an approved vaccine with booster administration from another manufacturer. This study will help inform re-vaccination schedules and public health decisions regarding the deployment of boosters for COVID variants.
“As the number of Americans receiving vaccines continues to grow, we need to think about long-term strategies for fighting the coronavirus,” said Anne Falcy, a professor of infectious diseases at URMC School of Medicine. “This effort will probably look like a vaccination program for others. Infection, Like the flu. This study is an important step and will show whether doses of various vaccines are safe, tolerated and sufficiently effective. Immune system Enough to repel reinfection with SAR-CoV-2 and its variants. ”
Falsey and Angela Branche, MD are co-directors of the URMC Vaccine and Treatment Evaluation Unit (VTEU). Coronavirus pandemic. Dr. David Dobrzynski, MD, assistant professor of infectious disease medicine at Falsey, Branche, and URMC, leads the Rochester site of research.
Coronavirus continues to circulate at a high rate around the world, and scientists speculate that COVID could evolve into a seasonal mutant virus that will remain with us in the coming years. Researchers speculate that the immune system can provide years of protection,, It is not yet known how long the vaccine immunity will last. As with other vaccines, the immune response to COVID weakens over time, amplifier Administered to keep the immune system ready to fight the infection.
The emergence of variants is another complication that will determine future coronavirus booster dosing strategies. At this time, Pfizer-Bio NTech and Moderna vaccines appear to be very effective against most of the identified COVID variants, including Indian variants that are widespread in South Asia. However, existing vaccines Variants may emerge that may even reduce the effectiveness of the vaccine or even circumvent the protection provided by the vaccine altogether, and may require a new version of the vaccine.
Optimization and distribution of COVID vaccines is an important public health priority. The National Institutes of Health, Centers for Disease Control and Prevention, and the World Health Organization prioritize “mixed schedule” research, and immunity is sufficiently enhanced if someone receives a booster from the original vaccine and another manufacturer. I am judging whether or not. If the results of this study show that they are effective, they often plague large-scale vaccination programs by eliminating the reliance on a single company for domestic and global vaccine supply. May help solve some.
The new NIAID-funded Phase 1/2 clinical trial will recruit two volunteer groups.
Individuals over the age of 18 who have not yet been vaccinated.And
Individuals 18 years and older who completed their first vaccination within the last 12 to 20 weeks.
Unvaccinated participants will receive the Moderna vaccine and will receive a booster dose of the same vaccine or the Moderna variant vaccine 12 weeks later. Volunteers who have already been vaccinated with either Moderna, Pfizer Bio-NTech, or Johnson & Johnson will receive a booster modelna vaccine. The survey aims to enroll 500 US participants, including about 50 local volunteers.
“One of the key scientific questions we are trying to answer is that vaccines that use different platforms such as mRNA, adenovirus, and protein bases can sufficiently enhance the original immune response generated by the different platforms. Is it vaccine “Regardless of the manufacturer, boosting the immune response to COVID and its variants will help in future vaccination planning,” said Branche.
Quote: A new study mixes vaccine doses to boost immunity to COVID and variants (June 9, 2021)
This document is subject to copyright. No part may be reproduced without written permission, except for private research or fair trade for research purposes. The content is provided for informational purposes only.
Source link A new study combines vaccine doses to boost immunity to COVID and its variants
A new preprint study posted to the medRxiv* server shows an AstraZeneca’s ChAdOx1-nCov-19 and Pfizer/BioNTech BNT162b2 COVID-19 vaccine combination is immunologically superior to two AstraZeneca ChAdOx1-nCov-19 doses.
Led by German researchers, the study shows that having the first dose with AstraZeneca’s ChAdOx1 and the second with Pfizer/BioNTech BNT162b2 elicits significantly higher anti-spike titers and more neutralizing activity against B.1.1.7, P.1, and B.1.351 variants.
Both P.1 and B.1.351 variants have mutations that allow them to evade vaccine-induced immunity — increasing the risk of spreading SARS-CoV-2 and developing severe illness or death. In response, there have been discussions amongst vaccine developers for creating booster shots against variants.
The findings suggest mixing and matching vaccine doses could be enough to boost the immune system against different variants of concern.
Immune response from the first dose wanes over time
The researchers used the COVID-19 Contact Study cohort of Healthcare Professionals to evaluate immune responses from the first dose of the AstraZeneca vaccine before and 3 weeks after choosing a second dose with either the same vaccine or the Pfizer/BioNTech dose.
About 129 people who received the first AstraZeneca dose were never infected with COVID-19. Of this group, 32 chose the same booster, and 55 chose the Pfizer/BioNTech booster.
Both groups had comparable anti-S IgG and IgA antibody levels against the spike protein before receiving their second dose. However, the boosted antibody levels from the first dose declined by almost half 30 days after receiving the first dose but before getting the second.
Stronger humoral immune response against all SARS-CoV-2 variants following heterologous ChAdOx1 nCoV-19 (ChAd) / BNT162b2 (BNT) than homologous ChAd / ChAd vaccination.
Greater antibody response with AstraZeneca/Pfizer/BioNTech combo
Regardless of the vaccine, both groups who received a second dose showed a boost in anti-S IgG and IgA responses.
Having the Pfizer/BioNTech vaccine as the second dose significantly increased anti-S IgG antibody levels by 11.5-fold compared to a 2.9-fold increase observed in people who received both AstraZeneca vaccines. Similar increases in anti-S IgA antibody levels were also observed, suggesting a better humoral immune response with mixed-match doses.
Increased neutralizing activity against SARS-CoV-2 variants
The researchers next looked at neutralization effectiveness against SARS-CoV-2 and recent variants of concern, including B.1.1.7, P.1, and B.1.351 variants.
Of 81 out of 88 participants, neutralizing antibodies against the Wuhan strain were found. However, there were fewer neutralizing antibodies for B.1.1.7, 7 (17/88), P.1 (12/88), and B.1.351 (5/88).
Two to 3 weeks after the second vaccine dose, the researchers observed increases in titers of neutralizing antibodies against the Wuhan strain in both groups — with the mix-match group showing the highest neutralizing titers.
Against the variants of concern, getting two doses of AstraZeneca showed some immune response towards the B.1.17 variant. However, it was not effective against P.1 or B.1.351.
Getting a second Pfizer/BioNTech dose increased neutralizing antibodies against all variants of concern. The AstraZeneca- Pfizer/BioNTech group had the highest neutralizing response against the Wuhan strain, followed by the B.1.1.7 variant. While some neutralization was observed, the mixed-match doses were less efficient against the P.1 and B.1.351 variants.
“Altogether, these data indicate that the booster immunization led to an increase of neutralizing antibodies in both vaccination groups and that the heterologous ChAdOx/BNT booster booster vaccination efficiently induced neutralizing antibodies against all tested VoC.”
Higher number of B cells in Pfizer/BioNTech combo group
S-specific B cells strongly increased, and an increase in recent isotype switched B cells (IgD–IgM–) was observed in people who received Pfizer/BioNTech as a second dose.
The increase in B cells specific to the spike protein after receiving the Pfizer/BioNTech booster corresponded with neutralizing power against the variants of concern.
There were also greater increases in S-specific CD4 T cells and S-specific IFN-γ release in the mixed-matched group.
The results suggest mixing booster shots elicits a more significant immune response against SARS-CoV-2. However, more work is needed to characterize immune responses further. It would also help to understand how long vaccine immunity lasts and whether mixed-match doses provide a more robust immune response over time.
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.