Smoking, central obesity, hypertension may lower antibody response to COVID-19 vaccine

Smoking, central obesity, hypertension may lower antibody response to COVID-19 vaccine

  • June 15, 2021


Disclosures:
The authors report no relevant financial disclosures.


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Compared with healthy adults, those who smoke or have central obesity or hypertension may produce fewer antibodies following Pfizer-BioNTech COVID-19 vaccination, according to a study published in Diabetes/Metabolism Research and Reviews.

Mikiko Watanabe

“Patients with central obesity, hypertension and smoking habit respond in a different way to Pfizer-BioNTech COVID-19 vaccine, where antibody titers are significantly lower compared to healthy subjects,” Mikiko Watanabe, MD, PhD, a specialist in endocrinology and metabolism at Sapienza University in Rome, told Healio. “Although lower antibody titers do not necessarily mean that protection against COVID-19 is hampered, it is necessary to plan follow-up studies to investigate this aspect, also considering the possibility that these patients might require earlier vaccine boosters over time.”



Central obesity, smoking, hypertension and dislipidemia were associated with fewer COVID-19 antibodies in people receiving the Pfizer-BioNTech COVID-19 vaccine. Data were derived from Watanabe M, et al. Diabetes Metab Res Rev. 2021;doi:10.1002/dmrr.3465.

Watanabe and colleagues conducted an observational study of 86 health care workers (mean age, 29 years; 39.5% men) at Policlinico Umberto I in Rome who received the Pfizer-BioNTech COVID-19 vaccine in January and February. All participants were older than 18 years, had stable body weight during the previous 3 months, had no previous COVID-19 infection, did not have immunodepression or use any medications known to affect the immune system and were not pregnant. Two doses of the vaccine were administered 21 days apart. Participants had blood drawn before the first dose and again 1 to 4 weeks after the second dose.

No major adverse events requiring hospitalization were reported after vaccination. Waist circumference, waist-to-hip ratio, BMI and body fat were not associated with more adverse events.

After the second dose, larger waist circumference was associated with fewer antibody titers (P = .004). Adults with hypertension had fewer antibodies compared with those without hypertension (650 U/mL vs. 1,911 U/mL; P = .001). Participants who habitually smoked had fewer antibodies vs. nonsmokers (1,099 U/mL vs. 1,921 U/mL; P = .007). Those with dyslipidemia also had fewer antibodies compared with those who had a normal lipid profile and were not on lipid-lowering drugs (534 U/mL vs. 1,872 U/mL; P = .005).

“We did not expect smoking to be a risk factor for lower antibody titers, as there is virtually zero available evidence suggesting that smoking is associated with reduced response to vaccines,” Watanabe said. “Conversely, we expected patients with central obesity being less protected similar to what observed by our team in a previous study regarding the association between central obesity and need of intubation in patients with COVID-19.”

In a multivariate model adjusting for sex, age and BMI, waist circumference, time since last vaccination, hypertension and smoking were significantly associated with fewer COVID-19 antibodies after vaccination.

Watanabe said more studies with a larger sample size and participants with more diverse BMI are needed, and cell-mediated immunity must be examined to confirm the study’s findings.

“Should these preliminary data be confirmed, identifying ways to boost the immune system so that these patients respond better to the vaccine is definitely advisable,” Watanabe said.

For more information:

Mikiko Watanabe, MD, PhD, can be reached at mikiko.watanabe@uniroma1.it.

Delaying a COVID vaccine’s second dose boosts immune response

Delaying a COVID vaccine’s second dose boosts immune response

  • June 4, 2021

Facing a limited vaccine supply, the United Kingdom embarked on a bold public-health experiment at the end of 2020: delaying second doses of COVID-19 vaccines in a bid to maximize the number of people who would be at least partially protected from hospitalization and death.

Now, a study suggests that delaying the second dose of the Pfizer–BioNTech mRNA vaccine could boost antibody responses after the second inoculation more than threefold in those older than 801.

It is the first direct study of how such a delay affects coronavirus antibody levels, and could inform vaccine scheduling decisions in other countries, the authors say. “This study further supports a growing body of evidence that the approach taken in the UK for delaying that second dose has really paid off,” Gayatri Amirthalingam, an epidemiologist at Public Health England in London and a co-author of the preprint, said during a press briefing.

Many COVID-19 vaccines are given in two doses: the first initiates an immune response, and the second, ‘booster’ shot strengthens it. Clinical trials of the three vaccines used in the United Kingdom generally featured a three- to four-week gap between doses.

But for some existing vaccines, a longer wait between first and second doses yields a stronger immune response. Delaying the COVID-19 booster shots could also expand partial immunity among a greater swathe of the population than could the shorter dosing schedule. On 30 December, the United Kingdom announced that it would delay the second dose by up to 12 weeks after the first.

To determine whether the delay paid off, Amirthalingam and her colleagues studied 175 vaccine recipients older than 80 who received their second dose of the Pfizer vaccine either 3 weeks or 11–12 weeks after the first dose. The team measured recipients’ levels of antibodies against the SARS-CoV-2 spike protein and assessed how immune cells called T cells, which can help to maintain antibody levels over time, responded to vaccination.

Peak antibody levels were 3.5 times higher in those who waited 12 weeks for their booster shot than were those in people who waited only 3 weeks. Peak T-cell response was lower in those with the extended interval. But this did not cause antibody levels to decline more quickly over the nine weeks after the booster shot.

The results are reassuring, but are specific to the Pfizer vaccine, which is not available in many low-to-middle income countries, says Alejandro Cravioto, chair of the World Health Organization’s Strategic Advisory Group of Experts on Immunization. Countries will need to consider whether the variants that are circulating in their particular region might raise infection risk after only one vaccine dose, he says.

For the United Kingdom, extending the interval between doses was clearly the right choice, but the country’s lockdown deserves part of the credit for that success, says Stephen Griffin, a virologist at the University of Leeds, UK. “People are theoretically vulnerable between their first and second jab,” he says. “What’s worked in the UK is maintaining restrictions at the same time as vaccinating.”

New Drug May Bypass SARS-CoV-2 Blockade Of Innate Immune Response

New Drug May Bypass SARS-CoV-2 Blockade Of Innate Immune Response

  • June 3, 2021

Scientists have identified a small molecule drug that might prevent and treat Covid-19 by targeting a cellular gene that bypasses SARS-CoV-2 blockade of the innate immune response. The drug, diABZI, is currently undergoing phase II clinical trials as a potential cancer treatment.

So far, the search for Covid-19 drugs has yet to yield a product comparable in efficacy and utility to the mRNA vaccines created by Moderna and Pfizer. Remdesivir and monoclonal antibodies, the two FDA-approved treatments we currently have on hand, may be moderately effective, but they can only be administered intravenously in hospital settings. 

Early on in the pandemic, experts thought interferon-based drugs would make a potent Covid-19 treatment. Interferon is a signaling protein the body relies on to activate critical immune sensing pathways, and studies showed that SARS-CoV-2 either actively inhibited or evaded it. If a virus goes to great lengths to avoid triggering interferon, it makes logical sense that loading up on interferon would succeed as a countermeasure. But clinical trials testing interferon drugs fell short of expectations, yielding mixed results.

Interferon may have been an obvious choice, but obvious in theory doesn’t always translate to success in practice. The problem isn’t necessarily that interferons don’t work. Using them so directly might just be too blunt an approach. New research, published in the journal Science Immunology in May 2021, suggests that using a small molecule drug to preemptively trigger the innate immune response downstream from interferons—specifically, the STING pathway—might do the trick instead.

Immunity typically transpires in two waves. The first line of defense the virus encounters when it enters the body is the innate immune response, followed by an adaptive immune response that mobilizies T cells and B cells to recognize and attack specific pathogens. Innate immunity is necessary to trigger adaptive response.

Innate immunity involves proteins known as pattern-recognition receptors that, over the course of evolution, have been hard-wired to identify pathogen-associated molecular patterns, or PAMPs. Some of the better known PAMPs include bacterial lipopolysaccharides, acids, bacterial DNA, and both single- and double-stranded RNA.

A Science Immunology study led by microbiologist Sara Cherry and her colleagues at the University of Pennsylvania is the latest to show that the virus can evade these receptors adroitly enough to delay innate immunity for a significant period of time. To document this delay, the team infected respiratory cells with SARS-CoV-2 and monitored them for antiviral activity. A full 24 hours later, the cells exhibited very few transcriptional changes. It took 24 hours more—48 hours total—for innate immunity to kick into gear and begin expressing interferon-stimulated genes.

The suppression of gene expression is evidence of immune evasion, but not necessarily antagonism—a recurring theme throughout this research paper. The 24-hour timeline may be hypothetical, but the evolutionary advantage these mechanisms give the virus is not. So long as SARS-CoV-2 eludes detection, it can replicate unimpeded across the ACE2 receptors of bodily tissues and exit the body via nasopharyngeal and gastrointestinal passages, dispersing into the air and entering new hosts.

Across several more laboratory experiments, Cherry and her research team observed SARS-CoV-2 evading immune sensing pathways, interferon activation, and detection by pattern-recognition receptors. If a drug could stimulate these pathways independently, they reasoned, it might bypass viral suppression of the initial immune response. A second Science Immunology study, released at the same time as Cherry’s but conducted by a team from the University of Massachusetts, had the same hypothesis.

The target selected for both studies was the Stimulator of Interferon Genes, otherwise known as STING. Interferons induce STING, which in turn activates a cascade of downstream factors, including STAT6 and IRF3, through the coding gene TBK1. Activation of the STING pathway leads to activation of both the innate and adaptive immune response, suppressing viral replication before it can overwhelm our bodily systems.

Critically, the STING pathway appears to bypass the many blockades SARS-CoV-2 mounts against the innate immune response. Spurred by this observation, Cherry and her team screened 75 potential STING agonists for their ability to block SARS-CoV-2. Of all the candidates, nine suppressed infection more than tenfold. Two cyclic dinucleotides showed particular promise but, as negatively charged molecules, they crossed the cell membrane at too inefficient a rate to warrant further examination.

Instead, Cherry and her team chose diamidobenzimidazole, or diABZI, a small molecule drug that mimics cyclic dinucleotides in most respects—except it readily crosses the cell membrane. It is currently in trials for cancer treatment. The University of Massachusetts researchers chose diABZI-4, a new compound of the same drug. Both studies found that diABZI potently inhibited infection in both cell cultures and mice models, inducing the expression of hundreds of antiviral genes the virus would otherwise delay.

Cherry and her team treated respiratory cells with diABZI and observed that it induced expression of more than 400 genes, nearly 40 percent of which link back to interferon signaling pathways. Compared to cells treated with interferon beta, upregulation of interferon-stimulated genes in diABZI-treated cells was more transient—meaning the risk of overstimulation is much less. Despite differences in duration, diABZI still suppressed the virus at a potency comparable to type I interferon treatment, blocking SARS-CoV-2 replication about 1000-fold in air-liquid interface cultures.

In mice models, the results were even more promising. A single dose, delivered intranasally six hours prior to infection, helped prevent early weight loss and enable their full recovery. Rather than an oral or intravenous point of entry, the researchers focused on the respiratory tract because it is typically the first site of infection and, once the immune system is activated, the first line of defense. In subsequent dose-response experiments, even the lowest dose of diABZI resulted in about 1000-fold inhibition. The potency of the immune reaction triggered by diABZI, the researchers also found, was as robust against the B.1.351 (South Africa) strain as the original (Wuhan) strain. This suggests the treatment might be effective at deterring respiratory viruses more broadly.

The Science Immunology studies mostly focused on diABZI as a potential prophylactic—a drug administered prior to infection, with the aim of prevention. But given to the mice therapeutically, with the aim of mitigating the severity of symptoms post-infection, diABZI still proved effective at reducing viral loads. Furthermore, unlike monoclonal antibody drugs, use of a chemical-based drug like diABZI isn’t affected or restricted by antibody resistance.

These are just the kinds of drug treatments we need to deter a virus as wily and elusive as SARS-CoV-2—powerful, broadly protective, and capable of disarming the virus with molecular precision, from multiple directions.

Delaying second Pfizer COVID-19 shot boosts immune response in over-80s, study finds

Delaying second Pfizer COVID-19 shot boosts immune response in over-80s, study finds

  • June 3, 2021

Delaying the second dose of the Pfizer–BioNTech COVID-19 vaccine by 12 weeks after the first dose significantly boosts antibody responses in elderly people, according to a new U.K. study.

Researchers from the University of Birmingham and Public Health England (PHE) found that peak antibody levels were 3.5 times higher in those who waited 12 weeks for their booster shot, compared with those who had it after a three-week gap.

The study, which was published as a preprint and hasn’t yet been peer-reviewed, will lend support to the U.K. government’s decision at the start of its COVID-19 vaccine rollout in December 2020 to delay second doses of the vaccines to inoculate the elderly and vulnerable quicker, and ease the tight supplies.

Read: U.K. health service pushes back interval for delivering second Pfizer coronavirus vaccine to a duration company says is untested

At the time, the strategy divided experts, as drug regulators had authorized use of both the shot developed by drug company Pfizer
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and its partner BioNTech
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and the shot produced by drug company AstraZeneca
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with the University of Oxford on the basis of clinical trials that had spaced out the doses by only three or four weeks.

“This study further supports a growing body of evidence that the approach taken in the U.K. for delaying that second dose has really paid off,” said Dr. Gayatri Amirthalingam, a PHE epidemiologist and a co-author of the study, to reporters at a briefing.

Researchers said the study of 175 people aged 80 and over is the first direct comparison of how such a delay affects the immune response in any age group for the different intervals. An earlier study from the University of Oxford found that a single dose of the AstraZeneca–Oxford vaccine provides a high level of protection when boosters of the shot were delayed for 12 weeks.

Read: CDC committee recommends that Pfizer’s COVID-19 shot be used in 12- to 15-year-olds

The Birmingham researchers also looked at another part of the body’s immune response, found in T cells, which destroy any cells that have been infected with the virus. The peak T cell responses were higher in the group with a three-week interval between doses, the researchers found, but they cautioned that it wasn’t yet clear how protected individuals were based on which dosing schedule they received. “Research is required to further explore these variations in responses, the authors noted.

Read: Mixing Pfizer and AstraZeneca COVID-19 vaccines increases mild side effects but is safe, study shows

Separately on Friday, PHE said that COVID-19 vaccinations in the U.K, had directly prevented an estimated 11,700 deaths of people aged 60 and over by the end of April, and kept 33,000 people aged 65 and older out of hospital.

“As these figures highlight, getting your vaccine could save your life or stop you becoming seriously ill from COVID-19. It will also significantly reduce your chances of getting infected and infecting others,” said Dr. Mary Ramsay, PHE’s head of immunization.

“It is vital to get both doses of your vaccine when you are offered it,” she added.

Person getting vaccinated.

Tips to improve our immune response after vaccination against COVID-19 – Explica .co

  • May 29, 2021

Vaccines are one of the health measures that have provided the greatest benefit to humanity. They have made it possible to prevent diseases responsible for major epidemics throughout history, such as smallpox.

Just over a year ago, COVID-19 was added to this list. Today we need vaccination again to be able to stop the spread of the coronavirus and regain normalcy.

Available vaccines have been shown to be effective in preventing the disease. However, the magnitude and quality of the immune response to vaccines varies considerably between individuals.

They are several factors that can influence in response to a vaccine.

Some refer to individual characteristics, such as age, sex, their genetic information and the presence of other pathologies (such as diabetes and cardiovascular diseases, both linked to alterations in the immune system).

But, in addition, our immune response to vaccines can vary depending on daily practices in our day to day.

What habits can improve our immune response after vaccination?

One of the key factors to promote the proper functioning of our immune system is sleeping a sufficient number of hours, as well as controlling our stress level.

Correct sleep hygiene allows to properly maintain biorhythms that control the production of hormones that regulate the function of the immune system, such as melatonin.

This hormone is produced during the night and its administration has been linked to lymphocyte survival and increased antibody production.

In fact, several studies have shown how insufficient sleep hours, both in the days before and after vaccination, can reduce the effectiveness of vaccines.

Stressful situations promote the release of hormones that suppress immune function, like cortisol, and are associated with a decreased response to vaccination.

Alternatively, activities that provide us satisfaction, such as sports or social relationships, favor the release of hormones that stimulate the immune system, such as endorphins.

Consistent with this idea, individuals who regularly exercise moderately and in a positive mood at the time of vaccination develop an increased response of antibodies and other immune response-enhancing molecules (such as cytokines).

Person getting vaccinated.Our immune response to vaccines can vary depending on our daily practices. (Photo: Getty Images)

The importance of eating well

Another crucial aspect to improve the effectiveness of a vaccine is to have an optimal nutritional status. There are several nutrients whose link with the immune system has been scientifically proven.

This is the case of vitamin C and folic acid, both with an important role in the production of effective molecules against infection.

Also the creation of collagen, which contributes to the maintenance of our natural barriers against pathogens.

However, studies suggest that isolated nutrient deficiencies appear to have little impact on response to vaccines, whereas a balanced diet, with a balanced supply of energy, seems to be key to strengthening the immune system.

In fact, people with high body mass indexes, and even obese, have lower production of antibodies, T lymphocytes and cytokines after vaccination.

It is also worth considering the relationship between the gut microbiota and responses to vaccines.

The microbiota associated with the intestinal tract plays key roles in protecting against the invasion of pathogenic microbes and regulating the immune system.

This microbiota is home to millions of microorganisms, mainly bacteria from the Firmicutes and Bacteriodetes groups.

The composition of said microbiota is relatively stable, and under normal conditions it presents a greater abundance of Firmicutes, which is associated with a greater antibody response.

donutsdonutsA balanced diet, with a balanced intake of energy, seems to be key to strengthening the immune system. (Photo: Getty Images)

Antibiotics, tobacco and alcohol

However, some circumstances, such as the existence of some pathology, changes in diet or the use of antibiotics, can produce alterations in the microbiota that affect our response to vaccination.

In these situations, the consumption of probiotics that restore balance in our intestinal microbiota has shown potentially beneficial effects on the response to vaccination, although it seems to vary according to the bacteria used, the dose or the duration of administration.

Finally, tobacco use directly alters our line of defense in the respiratory mucosa, and has been associated with lower antibody production after receiving vaccines.

Likewise, excessive alcohol consumption has an undesirable immunosuppressive effect when we receive a vaccine; Furthermore, alcohol can alter the composition of our intestinal microbiota and the immune cells present there, favoring the entry of pathogens into our body.

The immune response to vaccination is variable in the population.

Some of the factors that can influence it correspond to daily habits that affect our immune status, and knowing them can help us to modify them in order to boost our immune system so that it responds effectively when we get vaccinated.

* Patricia López Suarez is a professor at the toImmunology Area of ​​the University of Oviedo. This artThe article originally appeared on The Conversation. You can read the original version here.

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Children's immune response more effective against COVID-19 -- ScienceDaily

Ultrasensitive blood test detects viral protein, confirms mRNA vaccine activates robust immune response — ScienceDaily

  • May 28, 2021

The carefully orchestrated dance between the immune system and the viral proteins that induce immunity against COVID-19 may be more complex than previously thought. A new study by investigators at Brigham and Women’s Hospital used an ultrasensitive, single-molecule array (Simoa) assay to detect extremely low levels of molecules in the blood and measured how these levels change over the days and weeks following vaccination. The team found evidence of circulating protein subunits of SARS-CoV-2, followed by evidence of the body mounting its immune response and then clearing the viral protein to below the level of single-molecule detection. Results are published in Clinical Infectious Diseases.

“Because of our ultra-sensitive method, we’re able to corroborate that the mRNA vaccine is operating as intended, stoking the body’s immune response,” said co-corresponding author David Walt, PhD, a member of the faculty in the Department of Pathology at the Brigham. Walt is also a member of the Wyss Institute and is a Howard Hughes Medical Institute Professor. “We were able to detect extremely low levels of viral protein and see that as soon as the body begins generating antibodies, those levels declined to undetectable.” Walt has a financial interest in Quanterix Corporation, the company that developed the ultra-sensitive digital immunoassay platform used in this work.

To conduct their study, Walt and colleagues measured levels of SARS-CoV-2 protein subunits in plasma samples collected from 13 participants who received two doses of the Moderna (mRNA-1273) vaccine. Specifically, the team measured levels of SARS-CoV-2 antigens Spike, S1, and Nucleocapsid. The team examined plasma collected at 10-13 timepoints between 1 and 29 days after the first injection and 1-28 days after the second injection. The average age of participants was 24 and the percentage of female participants was 46.

The team found that 11-of-13 participants had low levels of SARS-CoV-2 protein (S1 subunit) as early as one day post-vaccination. S1 subunit protein level peaked on average five days after the first injection. In all participants, the level of S1 protein declined and became undetectable by day 14. Spike protein was detected in 3-of-13 participants an average of 15 days after the first injection. After the second vaccine dose, no S1 or Spike was detectable.

The team collected corresponding antibody data and showed that the immune response began to mount after the viral proteins were produced. Increased antibody levels correlated with viral protein clearance from plasma.

The researchers note that the level of translated protein detected was extremely low and disappeared once antibodies were detected. All participants in the study were healthy volunteers who were vaccinated but not infected with SARS-CoV-2.

“The vaccine is designed to introduce mRNA into the body, which is then translated into the Spike protein. It is the Spike protein that can activate the immune system, which in turn creates antibodies to prevent future infections,” said co-first author Alana Ogata, PhD, a postdoctoral fellow in the Walt lab. “We observed that antibodies that target Spike and S1 proteins are generated as early as 1-2 days after circulating S1 is detected, followed by the clearance of proteins. Additionally, we see that the second dose does not result in circulating protein but does provide an additional boost in antibody levels, as expected.”

Researchers note that limitations of the current study include the small sample size and potential biases that result from enrolling healthy, young adults, which may not be representative of the general population. The research team plans to continue their plasma studies in other populations, including pregnant people and children, to further understand the dynamics between viral proteins and the immune response.

Funding for this work was provided by gifts to the Brigham from Amos and Barbara Hostetter and the Chleck Family Foundation. Walt is an inventor of the Simoa technology, founder of the company and serves on its Board of Directors. Walt’s interests were reviewed and are managed by Brigham and Women’s Hospital and Mass General Brigham in accordance with their conflict of interest policies. The anti-SARS-CoV-2 Simoa assays in this publication have been licensed by Brigham and Women’s Hospital to Quanterix Corporation.

Story Source:

Materials provided by Brigham and Women’s Hospital. Note: Content may be edited for style and length.

Studies suggest COVID immunity could last long after antibodies fade

COVID immunity: Studies suggest coronavirus immune response could last long after antibodies fade

  • May 27, 2021
NEW YORK — Two encouraging studies suggest that people who recovered from COVID-19 had immune responses to the virus long after antibodies faded, even up to one year later.

The findings may help put to rest lingering fears that protection against the virus will be short-lived.

Researchers in both studies examined bone marrow in volunteers who had been exposed to the coronavirus about a year earlier. They found that a part of the immune system called “B cells” seemed to stick around, providing the body with a biological “memory” of a coronavirus infection.

The study published online at BioRxiv, a site for biology research, found that these B cells continued to grow and strengthen at least 12 months later.

The other study was published in the journal Nature Monday.

Health officials have emphasized for months that COVID-19 vaccinations turbo-charge the body’s antibody response. In essence, a shot gives the body more antibodies than a natural infection would, and more antibodies are usually associated with longer protection, said Dr. William Schaffner, a professor in the Department of Health Policy at Vanderbilt University.

Experts, however, have no way to definitely know now how long protection from coronavirus lasts, as the virus is new and therefore hasn’t been studied over long periods of time. While the findings are optimistic, these studies also don’t take virus variants into account, Schaffner said.

And just because the studies show evidence of long-lasting immune responses doesn’t mean experts know how long complete protection lasts, said Dr. Dan Barouch from Beth Israel’s Center for Virology and Vaccine Research.

This means that despite promising results, booster shots may still be needed.

“I don’t anticipate that the durability of the vaccine protection is going to be infinite. It’s just not, so I would imagine we will need at some time a booster,” Dr. Anthony Fauci, the nation’s top infectious disease expert, said Wednesday during a Senate hearing.

ABC News contributed to this report.

Copyright © 2021 WLS-TV. All Rights Reserved.

New therapy extends breast cancer survival rate, prevents reoccurrence

Ultrasensitive blood test detects viral protein, confirms vaccine activates robust immune response

  • May 26, 2021

The carefully orchestrated dance between the immune system and the viral proteins that induce immunity against COVID-19 may be more complex than previously thought. A new study by investigators at Brigham and Women’s Hospital used an ultrasensitive, single-molecule array (Simoa) assay to detect extremely low levels of molecules in the blood and measured how these levels change over the days and weeks following vaccination. The team found evidence of circulating protein subunits of SARS-CoV-2, followed by evidence of the body mounting its immune response and then clearing the viral protein to below the level of single-molecule detection. Results are published in Clinical Infectious Diseases.

“Because of our ultra-sensitive method, we’re able to corroborate that the mRNA vaccine is operating as intended, stoking the body’s immune response,” said co-corresponding author David Walt, PhD, a member of the faculty in the Department of Pathology at the Brigham. Walt is also a member of the Wyss Institute and is a Howard Hughes Medical Institute Professor. “We were able to detect extremely low levels of viral protein and see that as soon as the body begins generating antibodies, those levels declined to undetectable.” Walt has a financial interest in Quanterix Corporation, the company that developed the ultra-sensitive digital immunoassay platform used in this work.

To conduct their study, Walt and colleagues measured levels of SARS-CoV-2 protein subunits in plasma samples collected from 13 participants who received two doses of the Moderna (mRNA-1273) vaccine. Specifically, the team measured levels of SARS-CoV-2 antigens Spike, S1, and Nucleocapsid. The team examined plasma collected at 10-13 timepoints between 1 and 29 days after the first injection and 1-28 days after the second injection. The average age of participants was 24 and the percentage of female participants was 46.

The team found that 11-of-13 participants had low levels of SARS-CoV-2 protein (S1 subunit) as early as one day post-vaccination. S1 subunit protein level peaked on average five days after the first injection. In all participants, the level of S1 protein declined and became undetectable by day 14. Spike protein was detected in 3-of-13 participants an average of 15 days after the first injection. After the second vaccine dose, no S1 or Spike was detectable.

The team collected corresponding antibody data and showed that the immune response began to mount after the viral proteins were produced. Increased antibody levels correlated with viral protein clearance from plasma.

The researchers note that the level of translated protein detected was extremely low and disappeared once antibodies were detected. All participants in the study were healthy volunteers who were vaccinated but not infected with SARS-CoV-2.

“The vaccine is designed to introduce mRNA into the body, which is then translated into the Spike protein. It is the Spike protein that can activate the immune system, which in turn creates antibodies to prevent future infections,” said co-first author Alana Ogata, PhD, a postdoctoral fellow in the Walt lab. “We observed that antibodies that target Spike and S1 proteins are generated as early as 1-2 days after circulating S1 is detected, followed by the clearance of proteins. Additionally, we see that the second dose does not result in circulating protein but does provide an additional boost in antibody levels, as expected.”

Researchers note that limitations of the current study include the small sample size and potential biases that result from enrolling healthy, young adults, which may not be representative of the general population. The research team plans to continue their plasma studies in other populations, including pregnant people and children, to further understand the dynamics between viral proteins and the immune response.

###

Funding for this work was provided by gifts to the Brigham from Amos and Barbara Hostetter and the Chleck Family Foundation. Walt is an inventor of the Simoa technology, founder of the company and serves on its Board of Directors. Walt’s interests were reviewed and are managed by Brigham and Women’s Hospital and Mass General Brigham in accordance with their conflict of interest policies. The anti-SARS-CoV-2 Simoa assays in this publication have been licensed by Brigham and Women’s Hospital to Quanterix Corporation.

Paper cited: Ogata A et al. “Circulating SARS-CoV-2 Vaccine Antigen Detected in the Plasma of mRNA-1273 Vaccine Recipients” Clinical Infectious Diseases DOI: 10.1093/cid/ciab465

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

Common Immune Drug Methotrexate May Hamper Response to COVID-19 Vaccine | Health News

Common Immune Drug Methotrexate May Hamper Response to COVID-19 Vaccine | Health News

  • May 26, 2021

By Ernie Mundell and Robert Preidt HealthDay Reporters

(HealthDay)

WEDNESDAY, May 26, 2021 (HealthDay News) — A widely used medicine for autoimmune diseases may lower people’s immune response to the Pfizer mRNA COVID-19 vaccine, a new study suggests.

The drug, called methotrexate, is often given to patients with immune-mediated inflammatory conditions such as rheumatoid arthritis and psoriasis/psoriatic arthritis.

“Our findings suggest that different strategies may need to be explored in patients with immune-mediated inflammatory diseases taking methotrexate to increase the chances of immunization efficacy,” said a team led by Dr. Jose Scher of New York University Langone Health in New York City.

In this study, the researchers assessed the immune response to the mRNA Pfizer COVID-19 vaccine in 82 patients with immune-mediated inflammatory diseases. All of the patients were taking either methotrexate or an alternative “immunomodulator” drug (mainly drugs called TNF inhibitors and other biologics). For comparison, Scher’s team also looked at vaccine responses in a group of healthy people.

The vaccine triggered “adequate” antibody levels in up to one-third fewer of the patients taking methotrexate, compared with patients on other immunomodulatory drugs or in healthy people, the findings showed.

Adequate antibody levels were seen in more than 90% of the 208 healthy participants and the 37 patients on biologic or non-methotrexate oral treatments, but in only 62% of the 45 patients taking methotrexate, the study found.

The researchers also reported that the vaccine induced activated CD8+ T cell responses in healthy people and patients with immune-mediated inflammatory diseases not on methotrexate, but not in patients on methotrexate. T cells are another part of the body’s immune defense system.

The study has been accepted for publication in the journal Annals of the Rheumatic Diseases.

Scher stressed that this was an observational study and can’t prove that methotrexate use actually caused the dip in COVID-19 vaccine effectiveness. It also had a small sample size, only assessed one type of mRNA COVID-19 vaccine (the Moderna mRNA vaccine was not tested), and could have included patients with previously asymptomatic COVID-19 infections.

The researchers also noted that patients on methotrexate were generally older than the comparison group (average age 63 versus 49), and that may potentially explain some of the differences in immune response.

Dr. Diane Horowitz is a rheumatologist at Northwell Health in Manhasset, N.Y. She wasn’t involved in the new study, but said its findings are no reason for people who take methotrexate to give up on COVID-19 vaccines.

“For the majority of patients on methotrexate or other immunosuppressive medications, the COVID vaccine is strongly recommended,” Horowitz said. “These patients should contact their physician to determine the optimal timing of the vaccination.”

According to Horowitz, “the American College of Rheumatology recommends that, for patients who are taking methotrexate, that they skip the dose of methotrexate for one week after each mRNA-based COVID vaccination,” to help maximize their immune response to the shot.

Scher’s team agreed, saying that further study is needed “to determine whether additional doses of vaccine, dose modification of methotrexate, or even temporary discontinuation of this drug can boost immune response.”

SOURCES: Diane Horowitz, MD, division of rheumatology, Northwell Health, Manhasset, N.Y.; Annals of the Rheumatic Diseases, news release, May 25, 2021

Copyright © 2021 HealthDay. All rights reserved.

Common Immune Drug Methotrexate May Hamper Response to COVID-19 Vaccine - Consumer Health News

Common Immune Drug Methotrexate May Hamper Response to COVID-19 Vaccine – Consumer Health News

  • May 26, 2021

WEDNESDAY, May 26, 2021 (HealthDay News) — A widely used medicine for autoimmune diseases may lower people’s immune response to the Pfizer mRNA COVID-19 vaccine, a new study suggests.

The drug, called methotrexate, is often given to patients with immune-mediated inflammatory conditions such as rheumatoid arthritis and psoriasis/psoriatic arthritis.

“Our findings suggest that different strategies may need to be explored in patients with immune-mediated inflammatory diseases taking methotrexate to increase the chances of immunization efficacy,” said a team led by Dr. Jose Scher of New York University Langone Health in New York City.

In this study, the researchers assessed the immune response to the mRNA Pfizer COVID-19 vaccine in 82 patients with immune-mediated inflammatory diseases. All of the patients were taking either methotrexate or an alternative “immunomodulator” drug (mainly drugs called TNF inhibitors and other biologics). For comparison, Scher’s team also looked at vaccine responses in a group of healthy people.

The vaccine triggered “adequate” antibody levels in up to one-third fewer of the patients taking methotrexate, compared with patients on other immunomodulatory drugs or in healthy people, the findings showed.

Adequate antibody levels were seen in more than 90% of the 208 healthy participants and the 37 patients on biologic or non-methotrexate oral treatments, but in only 62% of the 45 patients taking methotrexate, the study found.

The researchers also reported that the vaccine induced activated CD8+ T cell responses in healthy people and patients with immune-mediated inflammatory diseases not on methotrexate, but not in patients on methotrexate. T cells are another part of the body’s immune defense system.

The study has been accepted for publication in the journal Annals of the Rheumatic Diseases.

Scher stressed that this was an observational study and can’t prove that methotrexate use actually caused the dip in COVID-19 vaccine effectiveness. It also had a small sample size, only assessed one type of mRNA COVID-19 vaccine (the Moderna mRNA vaccine was not tested), and could have included patients with previously asymptomatic COVID-19 infections.

The researchers also noted that patients on methotrexate were generally older than the comparison group (average age 63 versus 49), and that may potentially explain some of the differences in immune response.

Dr. Diane Horowitz is a rheumatologist at Northwell Health in Manhasset, N.Y. She wasn’t involved in the new study, but said its findings are no reason for people who take methotrexate to give up on COVID-19 vaccines.

“For the majority of patients on methotrexate or other immunosuppressive medications, the COVID vaccine is strongly recommended,” Horowitz said. “These patients should contact their physician to determine the optimal timing of the vaccination.”

According to Horowitz, “the American College of Rheumatology recommends that, for patients who are taking methotrexate, that they skip the dose of methotrexate for one week after each mRNA-based COVID vaccination,” to help maximize their immune response to the shot.

Scher’s team agreed, saying that further study is needed “to determine whether additional doses of vaccine, dose modification of methotrexate, or even temporary discontinuation of this drug can boost immune response.”

More information

The U.S. Centers for Disease Control and Prevention has more on mRNA COVID-19 vaccines.

SOURCES: Diane Horowitz, MD, division of rheumatology, Northwell Health, Manhasset, N.Y.; Annals of the Rheumatic Diseases, news release, May 25, 2021

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