Tag: covid variants

Categories : COVIDTags :

New SARS-CoV-2 Variant BA.2.86 not as Resistant to Antibodies as First Feared

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Image by Fusion Medical on Unsplash

Researchers studying the new SARS-CoV-2 variant BA.2.86 have found that the new variant was not significantly more resistant to antibodies than several other circulating variants. Their study, published in The Lancet Infectious Diseases, also showed that antibody levels to BA.2.86 were significantly higher after a wave of XBB infections compared to before, suggesting that the vaccines based on XBB should provide some cross-protection to BA.2.86.

The recently emerged BA.2.86 is very different from any other currently circulating variants. It includes many mutations in the spike gene, reminiscent of the emergence of Omicron.  The virus uses the viral spike to infect cells and is the main target for our antibodies.  When the spike mutates, it comes with the risk that our antibodies are less effective against this new ‘variant’, and therefore that our protection from infection is reduced and that vaccines may need to be updated.

“We engineered a spike gene that matches that of the BA.2.86 variant and tested the blood of Stockholm blood donors (specifically those donations made very recently) to see how effective their antibodies are against this new variant. We found that although BA.2.86 was quite resistant to neutralising antibodies, it wasn’t significantly more resistant than a number of other variants that are also circulating”, says Daniel Sheward, lead author of the study and Postdoctoral researcher in Benjamin Murrell’s team at Karolinska Institutet.

An important question is whether upcoming updated vaccines that are based on the XBB variant will boost protection against BA.2.86.  To determine whether antibodies triggered by infection with XBB may be effective against this new variant, Ben Murrell’s team also compared samples taken before and after XBB spread in Sweden.

“We also found that antibody levels to BA.2.86 were significantly higher after a wave of XBB infections compared to before, suggesting that the vaccines based on XBB should provide some cross-protection to BA.2.86. However, BA.2.86 was resistant to all available monoclonal antibody therapeutics that we tested,” says Daniel Sheward.

Public health agencies need to know what the current level of immunity to this new variant is, and whether the vaccines are sufficient must be updated.  Monoclonal antibodies also represent an important option for some patient groups, such as the immunocompromised – for the clinicians, it’s important to know which if any, monoclonal antibody therapeutics will be effective against the variants that are circulating.  

“I think the main message is that there is currently no reason to be alarmed over this new variant and that it’s probably a good idea to get a booster vaccine when they are offered.  However, another ‘omicron-like’ event is also a reminder that we shouldn’t get complacent”, says Benjamin Murrell, Principal researcher at the Department of Microbiology, Tumor and Cell Biology at Karolinska Institutet.

Source: Karolinska Institutet

Categories : COVIDTags :

How SARS-CoV-2 Evolved Past its Own Weaknesses

On By ModernMedia
Image from Pixabay

New research suggests that the first pandemic-accelerating mutation in the SARS-CoV-2 virus evolved as a way to correct vulnerabilities that were caused by the mutation that started the SARS-CoV-2 pandemic.

Published in Science Advances, this new evidence addresses important biological questions about two key mutations in the virus’ surface spike protein, say the researchers. It suggests that a spike protein mutation called D614G, which emerged a few months after the virus began spread among humans, was not an adaptation to humans. Instead, the mutation was an adaptation to the major changes that happened in the spike gene just before the pandemic, changes which allowed spread via respiratory transmission.

“This study has revealed that the first two genetic alterations in the evolution of the spike protein in SARS-CoV-2 are connected by their function, and this knowledge can improve our understanding of how the spike protein works and how the virus evolves, with important implications for vaccine design and effectiveness of COVID antibodies,” says Stephen Gould, professor of biological chemistry at the Johns Hopkins University School of Medicine, whose lab was studying the basic biology of the virus’s spike protein when the study began.

The initial mutation in the virus, Gould says, is known by scientists as the “furin cleavage site insertion mutation.”

Research by other scientists across the world has shown that this mutation enabled the virus’s spike protein to be cut and primed it for rapid infection of cells lining the airway.

While this initial mutation was essential in helping SARS-CoV-2 efficiently slip into human cells, the mutation’s effects weren’t all good, says Gould, as it cut the spike protein structure into two separate pieces.

According to Gould, this change disrupted other functions of the spike protein, creating evolutionary pressure for a second mutation to correct the disrupted functions of the spike protein while keeping the initial mutations’ rapid infection benefits .

In early 2020, researchers from the University of Toronto discovered a subsequent SARS-CoV-2 mutation, called D614G; however, its precise function was not known.

Gould, first author and graduate student Chenxu Guo, and the research team set out to understand the D614G mutation and its effect.

Working with dozens of blood samples from patients with COVID-19 hospitalized in April 2020 at the Johns Hopkins Hospital, Gould’s team isolated antibodies for the spike protein from the patients’ blood samples. Then, they used these antibodies to track the location of spike proteins in human cells genetically engineered to produce the spiky surface molecules.

They found that the D614G mutation redirects the spike protein and pulls the virus from the surface of human cells into a tiny compartment within the cell called a lysosome, which the spike protein reprograms into storage containers that are used to release infectious virus particles from the cell.

In addition, the D614G mutation caused a three-fold drop in the abundance of spike proteins at the cell surface.

“With less spike protein on the surface of virus-infected cells, it may be more difficult for the immune system to identify and kill those virus-containing cells,” says Gould.

The researchers caution that the study does not provide information about the still-debated origins of the virus. However, their work suggests that the two mutations likely arose in rapid succession.

The researchers are new examining whether spike protein mutations in more recent virus strains affect spike protein trafficking, studying the identity of the human proteins that deliver spike proteins to lysosomes, and researching how spike proteins convert lysosomes into compartments that release more virus.

Source: John Hopkins Medicine

Categories : COVID PaediatricsTags :

Children’s Nasal Epithelium Protective against Older COVID Variants

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Photo by Kelly Sikkema on Unsplash

An Australian study published in PLOS Biology suggests the nasal epithelium of children inhibits infection and replication of the ancestral strain of the SARS-CoV-2 virus and also the Delta variant, but not the Omicron variant.

Children are in general less susceptible to COVID, with a lower infection rate and milder symptoms than adults. However, the factors driving this apparent paediatric resistance to COVID infections remained unknown.

In order to better understand infection and replication of SARS-CoV-2 in children, Kirsty Short at University of Queensland, and colleagues, obtained samples of primary nasal epithelium cells from twenty-three healthy children aged 2–11 and fifteen healthy adults aged 19–66 in Australia. They exposed the cells of adults and children to SARS-CoV-2 and then observed the infection kinetics and antiviral responses in children compared to adults.

The researchers found that ancestral SARS-CoV-2 replicated less efficiently and was associated with a heightened antiviral response in the nasal epithelial cells of children. This lower viral replication rate was also observed with the Delta variant, but not the Omicron variant.

Study limitations included a small sample size, so future clinical studies will be needed to validate these preliminary findings in a larger population and to determine the role of other factors, such as antibodies in protecting children from SARS-CoV-2 infection. Additionally, paediatric protection from emerging variants has yet to be quantified.

The authors wrote, “We have provided the first experimental evidence that the paediatric nasal epithelium may play an important role in reducing the susceptibility of children to SARS-CoV-2. The data strongly suggest that the nasal epithelium of children is distinct and that it may afford children some level of protection from ancestral SARS-CoV-2.”

Short added, “We use nasal epithelial cells from children and adults to show that the ancestral SARS-CoV-2 and Delta, but not Omicron, replicate less efficiently in paediatric nasal epithelial cells.”

Source: Science Daily

Categories : COVID Immune SystemTags :

SARS-CoV-2 Variants are Evolving to Evade Human Interferons

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SARS-CoV-2 infecting a human cell
Infected cell covered with SARS-CoV-2 viruses. Source: NIAID

Researchers have investigated how antiviral proteins called interferons interact with SARS-CoV-2. The study, published in PNAS, focuses on how the innate immune system defends against this coronavirus, which appears to be adapting to evade this interferon response.

The study was the result of a collaborative effort, including the laboratories of Mario Santiago, PhD, associate professor of medicine and Eric Poeschla, MD, professor of medicine, both at the University of Colorado School of Medicine.

While the adaptive arm of the immune system robustly deals with infection by generating antibodies and T cells, the innate arm forms an earlier, first line of defence by recognising conserved molecular patterns in pathogens.

“SARS-CoV-2 just recently crossed the species barrier into humans and continues to adapt to its new host,” said Prof Poeschla. “Much attention has deservedly focused on the virus’s serial evasions of neutralising antibodies. The virus seems to be adapting to evade innate responses as well.”

The type I Interferon system is a major player in antiviral defence against all kinds of viruses. Virus-infected cells release type I interferons (IFN-α/β), which warn the body of the intrusion. Secreted interferons cause susceptible cells to express powerful antiviral mechanisms to limit viral growth and spread. The interferon pathway could significantly reduce the levels of virus initially produced by an infected individual.

“They are clinically viable therapeutic agents that have been studied for viruses like HIV-1 for years,” explained Prof Santiago. “Here we looked at up to 17 different human interferons and found that some interferons, such as IFNalpha8, more strongly inhibited SARS-CoV-2. Importantly, later variants of the virus have developed significant resistance to their antiviral effects. For example, substantially more interferon would be needed to inhibit the omicron variant than the strains isolated during the earliest days of the pandemic.”

The data suggests that COVID clinical trials on interferons, dozens of which are listed in clinicaltrials.gov, may need to be interpreted based on which variants were circulating when the study was conducted. Researchers say that future work to decipher which of SARS-CoV-2’s multitude of proteins might be evolving to confer interferon resistance may contribute in that direction.

Source: University of Colorado Anschutz Medical Campus

Categories : COVIDTags :

mRNA Vaccines Perform Better against Variants of Concern

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A comparison of vaccinations has demonstrated that mRNA vaccines perform better against variants of concern (VOCs) than viral vector vaccines. Although they all effectively prevent severe disease by VOCs, the research published in PLOS Medicine suggests that people receiving a viral vector vaccine are more vulnerable to infection by new variants.

The Pfizer-BioNTech and Moderna are mRNA vaccines, which deliver genetic code to the bodies’ cells, whereas Oxford/AstraZeneca and J&J are viral vector vaccines which uses a modified virus to deliver instructions. J&J is delivered as a single dose while the rest are administered two weeks apart.

Marit J. van Gils at the University of Amsterdam, Netherlands, and colleagues, took blood samples from 165 healthcare workers, three and four weeks after first and second vaccination respectively, and for J&J at four to five and eight weeks after vaccination. Samples were collected before, and four weeks after a Pfizer-BioNTech booster.

Four weeks after the initial two doses, antibody responses to the original SARS-CoV-2 viral strain were highest in recipients of Moderna, followed closely by Pfizer-BioNTech, and were substantially lower in those who received viral vector vaccines. Tested against the VOCs Alpha, Beta, Gamma, Delta and Omicron, neutralising antibodies were higher in the mRNA recipients than the viral vector recipients. Neutralisation ability against VOCs was reduced in all vaccine groups, with the greatest reduction against Omicron. The Pfizer-BioNTech booster increased antibody responses in all groups with substantial improvement against VOCs, including Omicron.

The researchers caution that their AstraZeneca group was significantly older, because of safety concerns for the vaccine in younger age groups. As immune responses tend to weaken with age, this could affect the results. This group was also smaller because the Dutch government halted use for a period.

Source: EurekAlert!

Categories : COVIDTags :

Scientists Pry Open Secrets of a Potent Antibody against COVID

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Even as the structure of SARS-CoV-2 changes with different variants of the virus (grey), the J08 antibody (blue) can still bind it, Scripps researchers showed. Credit: Scripps Research

Scientists have revealed the secrets of a potent antibody against SARS-CoV-2 that was discovered in COVID survivors. The antibody has a broadly neutralising effect, and is able to retain its efficacy against a wide range of variants – though not Omicron.

In 2021, Scripps Research and Toscana Life Sciences scientists screened the blood of 14 COVID-19 survivors to find the most potent antibodies against the SARS-CoV-2 virus. One of the most promising finds, now in stage II/III trials, was an antibody dubbed J08, which seemed to be capable of both preventing and treating COVID. 

Now, the same group has visualised exactly how J08 binds to different SARS-CoV-2 variants in different conformations, explaining what makes the monoclonal antibody so potent. The research, published in Proceedings of the National Academy of Sciences, suggests that the J08 antibody’s flexibility will likely keep it effective against future COVID variants.

“Even though we can’t predict what variants of COVID will emerge next, understanding the details of J08 reveals what works against the virus, and perhaps how we can engineer antibodies to be even more potent,” explained senior author Andrew Ward, PhD at Scripps Research.

On exposure to a virus like SARS-CoV-2, the body creates a variety of antibodies that bind to different sections of the virus to clear it from the body. There is considerable interest in why certain naturally produced antibodies such as J08 more effective than others. In the months after Ward and his collaborators first identified J08, it became clear that the antibody, unlike many others, was potent against a variety of COVID variants.

The researcher mapped the three-dimensional structure of J08 as it bound to the spike protein of SARS-CoV-2. J08 was confirmed to successfully attach to the Alpha, Beta, Gamma and Delta variants, preventing replication. However, J08 attached to the Omicron variant about 7 times more slowly, and then quickly detached. About 4000 times more J08 was needed to fully neutralise Omicron SARS-CoV-2 compared to the other variants.

“With variants other than Omicron, this antibody binds quickly and doesn’t come off for hours and hours,” says co-first author Gabriel Ozorowski, a senior staff scientist in the Ward lab at Scripps Research. “With Omicron, we were initially happy to find that it still binds, but it falls off very quickly. We identified the two structural changes that cause this.”

The team showed that, for all the variants, J08 binds to a very small section of the virus – a section that generally stays the same even as the virus mutates. Moreover, J08 could attach in two completely different orientations, like a key that manages to unlock a door whether it is right side up or upside down. 

“This small, flexible footprint is part of why J08 is able to withstand so many mutations – they don’t impact the antibody binding unless they happen to be in this one very small part of the virus,” said co-first author Jonathan Torres, lab manager of the Ward lab at Scripps Research.

The Omicron variant of SARS-CoV-2, however, had two mutations (known as E484A and Q493H) that changed the small area of the virus that directly interfaces with J08, anchoring it in place. Ward and his collaborators found that if just one of these mutations is present, J08 can still bind and neutralise the virus strongly, but mutations in both are what make it less effective against the Omicron variant.

The researchers said the new results support the continued clinical trials of the monoclonal antibody based on J08.

“I think we’re pretty confident that future variants won’t necessarily have both of these two critical mutations at the same time like Omicron,” remarked Ozorowski, “so that makes us hopeful that J08 will continue being very effective.”

Source: Scripps Research

Categories : COVID HIVTags :

SA Doctors Report SARS-CoV-2 Mutations in a Patient with HIV

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HIV Infecting a T9 Cell. Credit: NIH

In an article awaiting peer review, doctors in South Africa report on the case of a 22-year-old female with uncontrolled advanced HIV infection and a SARS-CoV-2 infection that lasted 9 months, during which time the virus accumulated more than 20 additional mutations. Antiretroviral therapy suppressed HIV and cleared the coronavirus within 6–9 weeks. 

One hypothesis for novel variants is that they arise in severely immunocompromised individuals. Being unable to clear the virus because of a weakened immune response results in a persistent infection, letting mutations accumulate – some of which may allow immune evasion. In one case, SARS-CoV-2 in a female leukaemia patient developed seven mutations over three months of infection.

The authors describe a case of persistent SARS-CoV-2 infection, lasting for at least 9 months, in a severely immunocompromised woman with HIV that had challenges with adherence to antiretroviral therapy.

In mid-September 2021, a female in her 20s was admitted to a tertiary hospital in Cape Town with a one-week history of sore throat, malaise, poor appetite and dysphagia. The patient was infected with HIV at birth. In January 2021, her antiretroviral therapy (ART) regimen had been changed to tenofovir, emtricitabine and efavirenz, but she had difficulty adhering. In August 2021 she moved from rural KwaZulu-Natal to Cape Town. She stated that she had not received a COVID vaccination.

“On physical examination, the patient was wasted but had no palpable lymph nodes,” the authors report. “She was awake and lucid, with no focal neurological deficits. She was not in respiratory distress with an oxygen saturation of 98% on room air. The cardiovascular and abdominal examinations, renal function, white cell count and liver enzymes were without abnormalities. Her CD4 count was 9 cells/μL and her plasma HIV viral load 4.60 log10 viral RNA copies/mL, indicating advanced HIV infection, poorly controlled by ART.

“During a prolonged hospital stay the patient experienced multiple complications requiring treatment. Following adherence counselling, antiretroviral therapy was reinitiated with a new regimen of tenofovir/efavirenz/dolutegravir a week after admission.” 

The patient tested positive for COVID on 25 September 2021, with genomic sequencing indicating the Beta variant. However, in October, the patient later revealed that she had tested positive for COVID in January 2021. On 25 November 2021, the patient’s HIV viral load was <50 copies/ml and a PCR test was negative for COVID. While there was no CD4 count performed, suppressed HIV replication and clearance of the SARS-CoV-2 infection suggest her immune system had recovered to some degree.

Phylogenetic analysis showed that the samples indicated an ongoing infection instead of re-infections. During the 9 months of infection, the virus acquired at least 10 mutations in the spike glycoprotein and 11 other mutations over and above the lineage-defining mutations for Beta.

The authors consider it unlikely that the novel variant described spread into the general population, and stress that it does not prove that any of the other novel variants originated from an immunocompromised host in this fashion.

Increased vigilance is warranted to benefit affected individuals and prevent the emergence of novel SARS-CoV-2 variants. They ascribed the detection of the case to good connections between sequencing laboratories, routine diagnostic laboratories and frontline clinicians.

The authors concluded that their experience “reinforces previous reports that effective ART is the key to controlling such events. Once HIV replication is brought under control and immune reconstitution commences, rapid clearance of SARS-CoV-2 is achieved, probably even before full immune reconstitution occurs. This underscores the broader point that gaps in the HIV care cascade need to be closed which will benefit other conditions and public health problems, too, including COVID.”

Categories : COVIDTags :

A New Variant, B.1.1.529, Emerges in South Africa

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Image by Quicknews

The National Institute for Communicable Diseases (NICD), yesterday confirmed that a new COVID variant, B.1.1.529, has been detected in South Africa. Initially detected in Botswana, 22 cases of variant B.1.1.529 have been recorded in the country following genomic sequencing. More cases are being confirmed as sequencing results come out. 

Detected cases and positivity rates are increasing quickly, particularly in Gauteng, North West and Limpopo. The UK government has acted rapidly to temporarily suspend all inbound flights from South Africa and neighbouring countries, and impose quarantines for recent arrivals.

“It is not surprising that a new variant has been detected in South Africa,” commented Prof Adrian Puren, NICD Acting Executive Director, adding that, “Although the data are limited, our experts are working overtime with all the established surveillance systems to understand the new variant and what the potential implications could be. Developments are occurring at a rapid pace and the public has our assurance that we will keep them up to date.”

‘Warp speed’ effort to track and understand variant
Dr Michelle Groome, Head of the Division of Public Health Surveillance and Response at the NICD said that provincial health authorities remain on high alert and are prioritising the sequencing of COVID positive samples.  A top priority is to track the variant more closely as it spreads: it was first identified in Botswana this month and has turned up in travellers to Hong Kong from South Africa. Scientists are also trying to determine the variant’s properties such as vaccine evasion and disease severity.

“We’re flying at warp speed,” said Penny Moore, Wits University virologist, whose lab is gauging the variant’s immunity evasion ability. While there are anecdotal reports of reinfections and cases in vaccinated individuals, “at this stage it’s too early to tell anything,” Moore cautioned.

“There’s a lot we don’t understand about this variant,” Richard Lessells, an infectious disease physician at the University of KwaZulu-Natal, said at a press briefing organised by South Africa’s health department on 25 November. “The mutation profile gives us concern, but now we need to do the work to understand the significance of this variant and what it means for the response to the pandemic.”

The variant’s apparent sharp rise in Gauteng is cause for alarm. Cases increased rapidly in the province in November, particularly in schools and among young people, according to Lessells. Genome sequencing and other genetic analysis found that the B.1.1.529 variant was responsible for all of 77 of the virus samples they analysed from Gauteng, collected between 12 and 20 November. Analysis of hundreds more samples are in the works. A previous variant, C.1.2, appeared in South Africa and had concerning mutations, but ultimately failed to replace Delta over the winter.

Fortunately, the variant has a spike mutation easily detected by fast genotyping tests as opposed to genome sequencing, according to Lessells. Preliminary data from these tests suggest that B.1.1.529 is spreading much wider than Gauteng. “It gives us concern that this variant may already be circulating quite widely in the country,” Lessells said.

Are vaccines effective against it?
As happened with the Beta variant, a similar effort is starting to study B.1.1.529. Moore’s team, which provided some of the initial data on Beta’s immunity-dodging, has begun work on B.1.1.529. They plan to test the virus’s ability to evade infection-blocking antibodies, as well as other immune responses. The variant harbours a high number of mutations in regions of the spike protein that antibodies recognise, potentially dampening their potency.

“Many mutations we know are problematic, but many more look like they are likely contributing to further evasion,” said Moore. There are even hints from computer modelling that B.1.1.529 could evade immunity conferred by T cells, Moore added. Her team hopes to have its first results in two weeks.

“A burning question is does it reduce vaccine effectiveness, because it has so many changes,” said Aris Katzourakis, who studies virus evolution at the University of Oxford, UK.

Researchers in South Africa will also study the disease severity of B.1.1.529, Lessells said, which is “the really key question”.

Sources: NICD, Nature

Categories : COVID Obstetrics & GynaecologyTags :

Delta Variant Causes Pregnancy Complications

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Source: Anna Hecker on Unsplash

Pregnant women have been a population of concern for physicians since the beginning of the COVID pandemic, and early on the frequency of caesarean delivery, preterm birth and pregnancy-related hypertension was reported to be increased in pregnant women who developed severe or critical illness from the novel coronavirus.

In May and June this year, there was a lull in COVID cases and hospitalisations, to the relief of physicians at the University of Alabama at Birmingham Hospital and their pregnant patients. However, the Delta variant soon caused a rise in cases, hospitalisations and deaths across the US state of Alabama. Along with this there was a seemingly higher number of pregnant patients with COVID in hospitals and intensive care units than in previous surges.

“We saw an alarming increase in pregnant patients hospitalised with the Delta variant in July and August,” said Akila Subramaniam, MD, associate professor in UAB’s Division of Maternal-Fetal Medicine. “Even more, many of our patients were delivering pre-term because of the effects of the virus on these women.”

Researchers tracked admission rates and maternal and neonatal outcomes of pregnant COVID patients at UAB Hospital from March 22, 2020, to Aug. 18, 2021. Outcomes were compared between pre-Delta and Delta groups, with preliminary findings seriousindicating  morbidity and adverse outcomes associated with the Delta variant and pregnancy.

Prior to the Delta variant, UAB Hospital saw the highest admission of pregnant women with active COVID in July 2020. A total of 28 pregnant patients were admitted that month, three of whom were admitted to the intensive care unit. In comparison, 39 pregnant patients, with 11 in ICU, were hospitalised in just the first 18 days of August.

“Pregnant women are a high-risk population with low-vaccination rates overall,” said Jodie Dionne, MD, associate director of UAB Global Health in the Center for Women’s Reproductive Health and associate professor in the Division of Infectious Diseases. “There is misinformation circulating that causes doubt in the vaccines or downplays the effect of the virus. This study highlights how dangerous contracting the virus, especially the Delta variant, can be for the mom and baby.”

From the study’s early findings, the UAB researchers emphasize recommendations from the Society of Maternal-Fetal Medicine, the American College of Obstetricians and Gynecologists, and the Centers for Disease Control and Prevention to vaccinate pregnant patients to mitigate severe perinatal morbidity and mortality.

The findings were published in the journal of Obstetrics and Gynecology.

Source: University of Alabama at Birmingham

Categories : COVID Immune SystemTags :

Differences in Natural and Vaccine-induced COVID Immunity Revealed

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Source: Fusion Medical Animation on Unsplash

A new study recently published in Nature has found that immune protection resulting from COVID protection creates lasting effects in memory B cells.

Unlike circulating antibodies, which peak soon after vaccination or infection only to fade a few months later, memory B cells can remain to ward off severe disease for decades. They also evolve over time, learning to produce successively more potent ‘memory antibodies’ that are more effective at neutralising the virus and with better adaptation to variants.

Though vaccination instils higher levels of circulating antibodies than natural infection, the study suggests that not all memory B cells are created equal. While vaccination gives rise to memory B cells that evolve over a few weeks, natural infection births memory B cells that continue to evolve over several months, producing highly potent antibodies adept at eliminating even viral variants.

Though the findings suggest an advantage from natural infection over vaccination, this does not outweigh the dangers of illness and death from COVID, the researchers warn.

“While a natural infection may induce maturation of antibodies with broader activity than a vaccine does – a natural infection can also kill you,” explained Professor Michel C. Nussenzweig, head of Rockefeller’s Laboratory of Molecular Immunology. “A vaccine won’t do that and, in fact, protects against the risk of serious illness or death from infection.”

When any virus enters the body, immune cells immediately release circulating antibodies, which decay at variable rates depending on the vaccine or infection. They may confer protection for months or years but then dwindle in number, allowing possible reinfection.

Long term protection is provided by memory B cells that produce memory antibodies. Studies suggest that memory B cells for smallpox last at least 60 years after vaccination; those for Spanish flu, nearly a century. And while memory B cells don’t necessarily block reinfection, they can prevent severe disease.

Recent studies have suggested that within five months of receiving a vaccine or recovering from a natural infection, some no longer retain sufficient circulating antibodies to keep the novel coronavirus at bay, but memory B cells remain vigilant. Until now, however, scientists did not know whether the vaccines could be expected to provide the sort of robust memory B cell response seen after natural infection.

Prof Nussenzweig and colleagues resolved to tease out any differences in memory B cell evolution by comparing blood samples from convalescent COVID patients to those from never-infected mRNA-vaccinated individuals.

Vaccination and natural infection elicited similar numbers of memory B cells, which rapidly evolved between the first and second dose of the Pfizer and Moderna vaccines, producing increasingly potent memory antibodies. But after two months, progress stalled. The memory B cells were present in large numbers and expressed potent antibodies, but the antibodies were not getting any stronger. Also, although some of these antibodies were able to neutralize Delta and other variants, there was no overall improvement in breadth.

The researchers found that in convalescent patients, however, memory B cells continued to evolve and improve up to one year after infection. With every memory B cell update, more potent and more broadly neutralising memory antibodies were coming out.

There are several potential reasons that memory B cells produced by natural infection might be expected to outperform those produced by mRNA vaccines, the researchers said.

It is possible that the body responds differently to viruses that enter through the respiratory tract than those that are injected. Or perhaps an intact virus goads the immune system in a way the vaccines’ spike protein antigens simply cannot. It may also be possible that the virus persists in the naturally infected for weeks, giving the body more time to mount a robust response. The vaccine, on the other hand, is flushed out of the body mere days after triggering the desired immune response.

Memory B cells appear to undergo limited bouts of evolution in response to mRNA vaccines, a finding which may have significant implications for booster shots. A booster with the current mRNA vaccine would likely stimulate memory cells to produce antibodies strongly protective against the original virus and somewhat less so against the variants, Prof Nussenzweig said.

“When to administer the booster depends on the object of boosting,” he said. “If the goal is to prevent infection, then boosting will need to be done after 6 to 18 months depending on the immune status of the individual. If the goal is to prevent serious disease, boosting may not be necessary for years.”

Source: Rockefeller University