Natural immunity protection by COVID-19 variant fades over time

 For someone previously infected with COVID-19, their risk of hospitalization or death is 88% lower for at least 10 months compared to those who had not been previously infected, according to a systematic review and meta-analysis published in The Lancet.

The analysis also suggests that the level and duration of protection against reinfection, symptomatic disease and severe illness is at least on a par with that provided by two doses of the mRNA vaccines (Moderna, Pfizer-BioNtech) for ancestral, alpha, delta and omicron BA.1 variants. The study did not include data on infection from omicron XBB and its sublineages.

"Vaccination is the safest way to acquire immunity, whereas acquiring natural immunity must be weighed against the risks of severe illness and death associated with the initial infection," says lead author Dr. Stephen Lim from the Institute for Health Metrics and Evaluation (IHME) at the University of Washington's School of Medicine, U.S..

As IHME co-author Dr. Caroline Stein explains, "Vaccines continue to be important for everyone in order to protect high-risk populations such as those who are over 60 years of age and those with comorbidities. This also includes populations that have not previously been infected and unvaccinated groups, as well as those who were infected or received their last vaccine dose more than six months ago. Decision makers should take both natural immunity and vaccination status into consideration to obtain a full picture of an individual's immunity profile."

Since January 2021, several studies and reviews have reported the effectiveness of past COVID-19 infection in reducing the risk of reinfection and how immunity wanes over time. But none has comprehensively assessed how long the protection after natural infection will last and how durable that protection will be against different variants.

To provide more evidence, the researchers conducted a review and meta-analysis of all previous studies that compared the reduction in risk of COVID-19 among non-vaccinated individuals against a SARS-CoV-2 reinfection to non-vaccinated individuals without a previous infection up to September 2022.

It included 65 studies from 19 countries and evaluates the effectiveness of past infection by outcome (infection, symptomatic disease, and severe disease), variant, and time since infection. Studies examining natural immunity in combination with vaccination (i.e., hybrid immunity) were excluded from the analyses.

Immunity fades over time

Analysis of data from 21 studies reporting on time since infection from a pre-omicron variant estimated that protection against reinfection from a pre-omicron variant was about 85% at one month—and this fell to about 79% at 10 months. Protection from a pre-omicron variant infection against reinfection from the omicron BA.1 variant was lower (74% at one month) and declined more rapidly to 36% at around 10 months.

Nevertheless, analysis of five studies reporting on severe disease (hospitalization and death) found that protection remained universally high for 10 months: 90% for ancestral, alpha, and delta, and 88% for omicron BA.1.

Six studies evaluating protection against omicron sub-lineages specifically (BA.2 and BA.4/BA.5) suggested significantly reduced protection when the prior infection was pre-omicron variant. But when the past infection was omicron, protection was maintained at a higher level.

"The weaker cross-variant immunity with the omicron variant and its sub-lineages reflects the mutations they have that make them escape built-up immunity more easily than other variants," says IHME co-author Dr. Hasan Nassereldine. "The limited data we have on natural immunity protection from the omicron variant and its sub-lineages underscores the importance of continued assessment, particularly since they are estimated to have infected 46% of the global population between November 2021 and June 2022. Further research is also needed to assess the natural immunity of emerging variants and to examine the protection provided by combinations of vaccination and natural infection."

The researchers note some limitations of their study, cautioning that the number of studies examining the omicron BA.1 variant and its sub-lineages and the number from Africa was generally limited. In addition, only limited data were available beyond 10 months after the initial infection. They also note that some information, such as past infection status and hospital admissions, was measured differently or incomplete, and could bias the estimate of protection.

Writing in a linked Comment, Professor Cheryl Cohen, National Institute for Communicable Diseases, South Africa, who was not involved in the study, says, "The high and sustained levels of protection conferred by previous infection against severe disease have important implications for COVID-19 vaccine policy. By September, 2021, global SARS-CoV-2 seroprevalence was estimated at 59%, with substantial variation in the proportion of immunity induced by infection or vaccination in different settings. Seroprevalence in Africa was estimated at 87% in December, 2021, largely as a result of infection.

"High levels of immunity are an important contributor to the lower levels of severity observed with infection caused by emerging omicron subvariants. As SARS-CoV-2 epidemiology shifts to more stable circulation patterns in the context of high levels of immunity, studies of the burden and cost of SARS-CoV-2 infection and risk groups for severe disease are needed to guide rational vaccination policy and decisions around prioritization in relation to other vaccine preventable diseases."

More information: Past SARS-CoV-2 infection protection against re-infection: a systematic review and meta-analysis, The Lancet (2023). www.thelancet.com/journals/lan … (22)02465-5/fulltext

https://medicalxpress.com/news/2023-02-comprehensive-evidence-natural-immunity-covid-.html

Cancer patients who don't respond to immunotherapy may lack crucial immune cells

 Immunotherapy has transformed cancer care. In advanced melanoma, for example, the most fatal form of skin cancer, the five-year survival rate has risen from less than 10% to more than 50% since immunotherapy was introduced in 2011. Still, only about half of melanoma patients respond to immunotherapy, and those who do not respond face a difficult future.

Researchers at Washington University School of Medicine in St. Louis have discovered that the difference between people who do and do not respond to immunotherapy may have to do with an immune cell known as CD5+ dendritic cells, because they bear the protein CD5 on their outer surfaces. The research showed that people with a variety of kinds of cancers, including melanoma, lived longer if they had more CD5+ dendritic cells in their tumors, and that mice that lacked CD5 on their dendritic cells were unable to respond well to immunotherapy.

The findings, published in the journal Science, suggest that a supplementary therapy designed to increase the number or activity of CD5+ dendritic cells potentially could extend the lifesaving benefits of immunotherapy to more cancer patients.

"Immunotherapy has revolutionized the field of cancer therapy, but there are a lot of patients with cancer who don't benefit from it," said senior author Eynav Klechevsky, Ph.D., an assistant professor of pathology & immunology and a researcher at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine.

"Part of the reason some people do not respond well to some forms of immunotherapy is because this population of dendritic cells is reduced dramatically. We're developing some novel immune-based approaches to boost the activation of these CD5-expressing dendritic cells with a goal of helping more patients respond to immunotherapy."

The immune system defends the body against cancer by activating immune cells known as T cells to recognize and kill tumor cells. In response, tumor cells manipulate the immune checkpoint system—a safeguard that prevents T cells from mistakenly attacking healthy cells—to hoodwink T cells into leaving them alone. Immune checkpoint blockade therapy works by thwarting tumor cells' manipulations, thereby freeing T cells to recognize and destroy tumors. But even with therapy, some people's T cells are unable to do their job effectively.

Klechevsky and colleagues—including first author Mingyu He, Ph.D., a staff scientist, and co-author Kate Roussak, MD, a postdoctoral researcher—suspected that people who don't respond to immunotherapy may have a problem with their dendritic cells. If T cells are the players on a soccer field, dendritic cells are the coaches who get the players pumped up for the game and give them instructions. Without dendritic cells, T cells are subdued and aimless.

By analyzing data in The Cancer Genome Atlas—a public database with information on 20,000 tumors representing 33 cancer types—Klechevsky and colleagues discovered that patients with types of skin, lung, bone and soft tissue, breast and cervical cancers fared better if they had higher levels of CD5+ dendritic cells in their tumors.

Further experiments with human cells and mice showed that CD5+ dendritic cells are required for effective T cell activity against tumors. CD5+ dendritic cells from people powerfully induced T cells to activate and multiply. Mice with tumors responded only weakly to immunotherapy and failed to reject the tumors if they lacked CD5 on their dendritic cells.

The findings suggest that the amount of CD5+ dendritic cells inside tumors could be used to help doctors assess which patients are most likely to benefit from immunotherapy. They also suggest that increasing the numbers or the activity of such dendritic cells potentially could help more people benefit from immunotherapy. As part of this study, the researchers discovered that the immune protein IL-6 increases the amounts of CD5+ dendritic cells.

"We still don't completely understand how immunotherapies work," Klechevsky said. "This study indicates that there is more we can do to increase the efficacy of these treatments. I'm confident that if we can find ways to harness these cells or expand these cells in patients, we can help more people."

More information: Mingyu He et al, CD5 expression by dendritic cells directs T cell immunity and sustains immunotherapy responses, Science (2023). DOI: 10.1126/science.abg2752

https://medicalxpress.com/news/2023-02-cancer-patients-dont-immunotherapy-lack.html

Moderna Pledges No Out-of-Pocket Costs for COVID Vaccines

 Moderna will join Pfizer in making its COVID-19 vaccine available for free once government coverage ends later this year, the company announced Wednesday.

The U.S. government has paid for the vaccines throughout the pandemic, but that will come to an end after the public health emergency concludes in May.

"Moderna remains committed to ensuring that people in the United States will have access to our COVID-19 vaccines regardless of ability to pay," the company said in a statement.

Pfizer previously announced plans for no out-of-pocket costs for people to get its COVID-19 vaccine.

The Moderna announcement comes amid criticism from lawmakers after The Wall Street Journal reported in January that the company planned to increase the price per vaccine dose to as much as $130. The U.S. government contract paid Moderna $26 per dose. 

Most insurance plans plus Medicare and Medicaid will cover the cost of vaccines with no out-of-pocket cost to participants, according to a recent summary from the Kaiser Family Foundation. But the organization noted that the transition to insurers paying the full cost of vaccines instead of the U.S. government could impact private insurance premiums.

Sources:

News release, Moderna.

Kaiser Family Foundation: "Commercialization of COVID-19 Vaccines, Treatments, and Tests: Implications for Access and Coverage."

Wall Street Journal: "Moderna Considers Price of $110-$130 for Covid-19 Vaccine."

https://www.medscape.com/viewarticle/988390

Jasper: Positive Data in in Sickle Cell Disease Study

 Data Presented in Plenary Session at the 2023 Transplantation & Cellular Therapy Meetings of the ASTCT and CIBMTR

• First two sickle cell disease participants have achieved 100% donor myeloid chimerism through 100 days follow-up

• Third sickle cell disease participant has now achieved 100% donor myeloid chimerism through 30 days follow-up

• All three participants have increased their hemoglobin at last follow-up relative to baseline
  

 Jasper Therapeutics, Inc. (Nasdaq: JSPR) (Jasper), a biotechnology company focused on developing novel antibody therapies targeting c-Kit (CD117) to address diseases such as chronic spontaneous urticaria and lower to intermediate risk myelodysplastic syndromes as well as novel stem cell transplant conditioning regimes, announced that additional follow-up data from Jasper’s investigator-sponsored study of briquilimab (formerly known as JSP191) as a conditioning agent in the treatment of sickle cell disease (SCD) were presented today in a plenary session focused on novel antibody-based conditioning regimens at the 2023 Tandem Meetings: Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR. Dr. John F. Tisdale, Director of the Cellular and Molecular Therapeutics Laboratory, National Heart, Lung, and Blood Institute, delivered the talk, titled “Improving the Landscape for Curative Therapies in Sickle Cell Disease with Novel Conditioning Methods.”

The study is a Phase 1/2 clinical trial (NCT05357482) evaluating the addition of briquilimab, Jasper’s anti-c-Kit monoclonal antibody, to an existing bone marrow transplantation regimen (NCT00061568) in individuals with SCD and beta thalassemia considered at high risk for complications from or ineligible for standard myeloablative hematopoietic stem cell transplant. The addition of briquilimab is being studied as a potential way to achieve a higher percentage of healthy donor stem cell engraftment (donor chimerism) without increased toxicity. Initial data from this study were previously shared by Jasper via press release on January 3, 2023.

https://finance.yahoo.com/news/jasper-therapeutics-announces-positive-clinical-210500705.html

iBio Announces MUC16 as its Latest Immune-Oncology Target Program

  iBio, Inc. (NYSEA:IBIO) (“iBio” or the “Company”), an AI-driven innovator of precision antibody immunotherapies, today announced the disclosure of MUC16 as the target of it’s latest immune-oncology program.

MUC16 is a well-known cancer target often overexpressed in several types of solid tumors, including ovarian, lung, and pancreas cancers. Specifically, MUC16 is a large extracellular protein expressed on more than 80% of ovarian tumors. Tumor cells can evade immune attack by shedding or glycosylating MUC16, making it difficult for traditional antibody therapies to effectively target and destroy the cancer cells.

Using its patented epitope steering AI platform, iBio's innovative approach to this challenge allows its new monoclonal antibodies (mAbs) to bind to a specific region of MUC16 that is not shed or glycosylated, circumventing both tumor evasion mechanisms and potentially providing a powerful tool in the fight against cancer.

"The targeting of a very specific, patho-physiologically relevant, region of MUC16 is a testament to the versatility of our AI technology, as it successfully shows it can be applied to a broad range of targets,” said iBio’s Interim Chief Executive Officer and Chief Scientific Officer, Martin Brenner. "This success adds to the growing list of target classes to which we have made differentiated antibodies using our patented epitope steering technology."

With the addition of the MUC16 program, iBio expands its Immuno-Oncology Portfolio complementing its Treg depleting programs IBIO-101 and CCR8, as well as its program targeting the tumor-specific EGFRvIII protein.

https://finance.yahoo.com/news/ibio-announces-muc16-latest-immune-214800108.html

US Military Readiness Under Scrutiny After Aerial Incursions

 by Andrew Thornebrooke via The Epoch Times (emphasis ours),

Over eight days and using five missiles, U.S. forces shot down four objects flying above U.S. and Canadian airspace.

Those objects include a Chinese spy balloon and three unidentified objects, one roughly the size of a Volkswagen Beetle and another an octagonal black-metallic object.

It’s a historic time for the North American Aerospace Defense Command, the joint American–Canadian organization responsible for overseeing North American airspace and its defense, which in its 65-year history had never before shot down an aerial object over North America.

The United States’ encounters with unidentified aerial phenomena (UAP) over the past two weeks, as well as pilots’ hardships in identifying and engaging with them, highlight glaring weaknesses in U.S. military readiness, according to several defense and security experts.

Such shortcomings included an apparent inability to detect one of the objects until it had already entered U.S. airspace, as well as a failure to track and engage another object that lingered near sensitive U.S. nuclear silos in Montana before evading further detection by fighter jets.

Paul Crespo, a former Marine officer at the Defense Intelligence Agency and now president of the Center for American Defense Studies, believes that the problem is largely due to the size, heat, and speed of the UAPs encountered in recent weeks, all of which factor into the ease with which they could be seen on radar.

“The recent flurry of unidentifiable aerial phenomena over the United States and Canada underscores our weakness in detecting and identifying nontraditional aerial threats,” Crespo told The Epoch Times in an email.

“If it isn’t made of metal, super hot, and traveling hundreds if not thousands of miles an hour, our air surveillance and defense systems appear stymied.”

Crespo’s comments highlight a problem addressed by the White House, which has acknowledged that the three UAPs had very small radar cross sections and were difficult to spot. It’s a small problem with big consequences.

US in ‘New Strategic Era’

The problem has been years in the making, according to Sam Kessler, a national security and geopolitical analyst with risk management firm North Star Support Group.

Because U.S. forces are trained to use radar primarily to detect other fighter craft, much-related technology and intelligence gathering hasn’t been honed to find objects that otherwise look either benign on radar or don’t appear at all.

“The detection issues are complicated since the sensing and radar technologies typically used for surveillance and detection purposes are usually set up under a different system of threats, such as the use of objects and vehicles that are typically fast-moving and carry a significant heat signature,” Kessler said.

https://www.zerohedge.com/political/us-military-readiness-under-scrutiny-after-aerial-incursions

WHO Suddenly Shelves Plans For Second Phase Investigation Into Origins Of COVID-19

 by Bill Pan via The Epoch Times,

More than three years after COVID-19 emerged in the Chinese city of Wuhan, the World Health Organization (WHO) has shelved its plan for the second phase of a study into the virus’ origins, Nature reported Tuesday.

In January 2021, a year after the initial outbreak, the WHO dispatched an international team of scientists and doctors from various disciplines to Wuhan, where they worked with Chinese experts to examine evidence about the virus. The phase one investigation yielded a report that only spawned more questions over the hypothesis that the virus might have escaped from the Wuhan Institute of Virology (WIV), which was tinkering with bat coronaviruses. It was also criticized for ignoring China’s failure to hand over complete, original data and samples.

In response to those concerns, the United Nations agency in July 2021 announced a plan for a more extensive second phase investigation. Specifically, it promised to find and review more data on “relevant laboratories and research institutions” in Wuhan, as well as data on wild animals sold at the city’s live animal markets in late 2019, to better understand whether it’s more likely that the pandemic began with human contact with an infected animal, or from a lab escape.

The proposed probe never materialized.

Dr. Maria Van Kerkhove, an epidemiologist at the WHO in Geneva, Switzerland, told Nature that the plan “has changed.”

“There is no phase two,” Van Kerkhove told the scientific journal.

“The politics across the world of this really hampered progress on understanding the origins,” she said.

In response to The Epoch Times’ request for further comments, a spokesperson for Van Kerkhove said Nature’s report was “incorrect” and that she has asked the publication for correction.

Nature has yet to issue any correction at the point of this publication.

CCP Pushback

The mere discussion of a lab escape as a possible scenario in the first phase report irritated the Chinese Communist Party (CCP) regime, which turned it into an excuse not to allow another WHO mission into Wuhan.

Just days after the WHO proposed a second phase investigation, the regime mounted a pushback, claiming that the lab breach hypothesis shouldn’t even be talked about, let alone be the focus of further scrutiny.

Security personnel keep watch outside the Wuhan Institute of Virology during the visit by the World Health Organization (WHO) team tasked with investigating the origins of the coronavirus disease (COVID-19), in Wuhan, Hubei Province, China, on Feb. 3, 2021. (Thomas Peter/Reuters)

The proposal, according to vice minister of China’s National Health Commission, Zeng Yixin, “did not respect common sense and violated science.” He also insisted that there wasn’t any “man-made virus” at the WIV, nor had the institute ever conducted gain-of-function experiments on the novel coronavirus.

“It is impossible for us to accept such an origin-tracing plan,” Zeng said at that time.

“We are opposed to politicizing the tracing work.”

Zeng’s comments prompted Washington to call out Beijing for its “dangerous” and “irresponsible” behavior.

“We are deeply disappointed,” said White House press secretary Jen Psaki said. “Their position is irresponsible, and frankly, dangerous. It’s not a time to be stonewalling.”

Amid the tension between China and the United States, the WHO was still seeking “directly engage” with Chinese officials and trying to establish collaborations with Chinese scientists, according to Van Kerkhove.

“We really, really want to be able to work with our colleagues there,” she told Nature. “It’s really a deep frustration.”

WHO Leadership Change

Nature’s report comes as Jeremy Farrar, a British pharmaceutical trust director involved in producing a paper arguing against the lab breach hypothesis, is set to take the helm of WHO’s science division.

According to emails obtained and publicized by independent journalist James Tobias via a Freedom of Information Act lawsuit, Farrar had been working on a draft of the paper with Dr. Anthony Fauci, who led the National Institute of Allergy and Infectious Diseases, in as early as January 2020. At one point, the two appeared to discuss whether the virus could have been put in a serial passage between animals in lab experiments and then escaped.

The paper in question, titled “The Proximal Origin of SARS-CoV-2,” was published in Nature Medicine in March 2020. It has since been widely cited by government officials—Fauci himself included—and mainstream media outlets as the scientific basis for dismissing the possibility that COVID-19 might have come out of a lab.

https://www.zerohedge.com/covid-19/who-suddenly-shelves-plans-second-phase-investigation-origins-covid-19-report