Category Archives: Immunology

Immunology

C.S. Mott Center teams with Chinese university to create new International Women Health Research Program – The South End

The C.S. Mott Center for Human Growth and Development at the Wayne State University School of Medicine has teamed with the Institute of Reproductive Health of Tongji Medical College at Huazhong University of Science and Technology in Wuhan, China, to establish the International Women Health Research Program.

The goal of the new collaboration is to improve womens treatment and care, particularly in the areas of cancer and reproductive health.

Maternal mortality, pregnancy complications such as preeclampsia and recurrent abortions, gynecologic cancers and infertility are still major global problems that can only be improved by international collaborations, said Gil Mor, M.D., Ph.D., director of the Mott Center and the John M. Malone Jr., M.D., Endowed Professor of Obstetrics and Gynecology. A womans reproductive aspects have a major impact not only on her health, but on the health of her children. The International Women Health Research Program will achieve its objectives by enhancing the education of health providers, investigators, students and general public.

Because the programs success depends on improving the education of physicians and researchers involved in multiple aspects of womens health, training investigators to develop novel approaches

for diagnosis and treatment, and educating the general population on the complex aspects related to reproduction and womens health, a key component of the collaboration includes exchange programs in which trainees, physicians and scientists train at the two participating institutions.

To date, in addition to developing three courses in reproductive immunology and one in ovarian cancer, the program has mentored 11 students in Wuhan, with two trained at WSU.

Under an internship program, physicians selected for the program are trained in the design and conduct of clinical and translational research in a 12-month program at the WSU School of Medicine. The partnership also includes support for training post-doctoral fellows for two years and the exchange of speakers for seminars at both institutions.

Throughout September, WSU and Huazhong University of Science and Technology virtually hosted a four-part lecture series for faculty of both schools featuring Dr. Mor speaking on reproductive immunology, implantation, infection in pregnancy and fetal-maternal immune interaction.

The collaboration has published eight papers, with more in various stages of pre-publication, and has secured one grant.

The universities held their first International Symposium for Reproductive Immunology and Genetics in Wuhan on May 18, 2017.

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Immunology

Boehringer Ingelheim and Oxford BioTherapeutics Expand Collaboration to Discover Novel Selective Tumor Targets as First Bispecific Antibody Advanced…

DetailsCategory: More NewsPublished on Wednesday, 14 October 2020 18:36Hits: 562

INGELHEIM, Germany and OXXFORD, UK I October 14, 2020 I Boehringer Ingelheim and Oxford BioTherapeutics Ltd. (OBT) today announced they are building on their successful partnership and are establishing a new alliance to discover additional selective targets for strategic cancer indications to deliver first-in-class treatments for cancer patients. Boehringer Ingelheim will use OBTs OGAP platform to identify novel target opportunities for new immunotherapies utilizing their T-cell engager, cancer vaccine and oncolytic virus platforms. This follows the initiation of the first patient dosing in a Phase 1 clinical trial of a bispecific antibody for the treatment of patients with small cell lung carcinoma and other neoplasms, where the target for the bispecific antibody was discovered during the first phase of the partnership.

This collaboration with Oxford BioTherapeutics is important for advancing therapeutic modalities that depend upon the identification of unique and specific tumor antigens within our cancer immunology portfolio, said Jonathon Sedgwick, Ph.D., Senior Vice President and Global Head Cancer Immunology & Immune Modulation Research at Boehringer Ingelheim. We are committed to developing innovative, efficacious and safe treatment options for patients suffering from cancer, and these novel cancer target discoveries are a key step in the development of new potential treatments.

We view the hopeful discovery of additional tumor targets as further confirmation of the value of our OGAP platform to identify novel targets that can be substrates for innovative new therapies, said Christian Rohlff, Ph.D., Chief Executive Officer of OBT. OBTs platforms are designed to discover and validate novel therapeutic targets and we look forward to continuing our partnership with Boehringer Ingelheim to best address difficult-to-treat cancers.

In addition to the programs in the partnership with Boehringer Ingelheim, OBTs clinical assets have also been enabled through the OGAP discovery platform. Selecting the right target is fundamental for the successful development of a truly first-in-class oncology product. OBTs platforms are designed to discover novel therapeutic targets and engineer antibodies to those targets, including CAR-T, other T-cell and NK cell-mediated cytotoxicity (ADCC) therapeutics to best address difficult-to-treat cancers. A major differentiator between OBTs discovery platform and other approaches is the retention of the link between individual patient samples through to the design of therapeutic antibodies and diagnostic patient selection tools, increasing the overall successful transition into clinical development.

Financial terms of the expanded agreement are not being disclosed. Under the terms of the agreement, Boehringer Ingelheim is responsible for the development and commercialization of antibody product candidates that interact with the novel targets identified by OGAP. OBT will receive development and regulatory milestone payments and royalties on any future product sales. To date, Boehringer Ingelheim has exercised two options under the first agreement and has selected two therapeutic candidates for further development.

Boehringer Ingelheim Oncology is taking cancer on by leading the science with cancer cell directed agents, immuno-oncology therapies and their combinations to address unmet needs in lung and gastrointestinal cancers. The company invests significantly in early stage research to identify unexplored and undrugged pathways of cancer. Learn more about Boehringer Ingelheims innovation in oncology here.

About Boehringer IngelheimMaking new and better medicines for humans and animals is at the heart of what we do. Our mission is to create breakthrough therapies that change lives. Since its founding in 1885, Boehringer Ingelheim is independent and family-owned. We have the freedom to pursue our long-term vision, looking ahead to identify the health challenges of the future and targeting those areas of need where we can do the most good.

As a world-leading, research-driven pharmaceutical company, more than 51,000 employees create value through innovation daily for our three business areas: Human Pharma, Animal Health, and Biopharmaceutical Contract Manufacturing. In 2019, Boehringer Ingelheim achieved net sales of19 billion euros. Our significant investment of almost 3.5 billion euros in R&D drives innovation, enabling the next generation of medicines that save lives and improve quality of life.

We realize more scientific opportunities by embracing the power of partnership and diversity of experts across the life-science community. By working together, we accelerate the delivery of the next medical breakthrough that will transform the lives of patients now, and in generations to come.

More information about Boehringer Ingelheim can be found at http://www.boehringer-ingelheim.com or in our annual report: http://annualreport.boehringer-ingelheim.com.

Boehringer Ingelheim in OncologyCancer takes. Takes away time. Takes away loved ones. At Boehringer Ingelheim Oncology, we are giving patients new hope, by taking cancer on. We are dedicated to collaborating with the oncology community on a shared journey to deliver leading science. Our primary focus is in lung and gastrointestinal cancers, with the goal of delivering breakthrough, first-in-class treatments that can help win the fight against cancer. Our commitment to innovation has resulted in pioneering treatments for lung cancer and we are advancing a unique pipeline of cancer cell directed agents, immuno-oncology therapies and intelligent combination approaches to help combat many cancers.

About Oxford BioTherapeuticsOxford BioTherapeutics is a clinical stage oncology company; based in Oxford, UK and San Jose, USA; with a pipeline of first-in-class immuno-oncology (IO) and antibody-drug conjugate (ADC) based therapies designed to fulfil major unmet patient needs in the field of cancer. OBT's IO discovery process provides unique insights into the cancer - immune cell synapse and has identified several novel IO candidates and bispecific antibodies for cancer therapy.

OBTs clinical lead program is OBT076 (MEN1309), currently in a U.S. Phase I Clinical Trial in Patients with Advanced Solid Tumors. OBT076 is in development for a number of tumors including HER2 negative breast cancer, triple-negative metastatic breast cancer, gastric, bladder, ovarian and lung cancer, where CD205 is overexpressed. Infiltration of primary localized breast tumors by immunosuppressive cells correlates with an adverse outcome (PFS and OS), suggesting they contribute to the progression of breast cancer and several other solid and liquid cancers.

OBTs pipeline and development capabilities have been validated through multiple strategic partnerships including with world leaders in antibody development (such as Amgen, Alere, BioWa, Medarex (BMS), Immunogen, Nerviano and WuXi) and Menarini. Additionally, one clinical and a second pre-clinical program are partnered with Boehringer Ingelheim. OBT has a strong oncology focused management team and board with significant experience in developing IO and antibody-based therapies.

For more information on Oxford BioTherapeutics, please visit http://www.oxfordbiotherapeutics.com (link is external).

SOURCE: Boehringer Ingelheim

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Immunology

Immune Systems Response to COVID-19 Was Just Revealed by Scientists Who Discovered SARS – SciTechDaily

In this study, which was recently published in the journal Frontiers in Immunology, researchers used sequencing to characterize the immune system of patients who survive from COVID-19 infection from symptom onset through recovery. Importantly, they also identified a potent biomarker for predicting disease progression. Follow-up studies could lead to the development of a treatment for COVID-19 that is inspired by our own immune system.

The study was led by Ling Chen and Nanshan Zhong of the National Clinical Research Center for Respiratory Disease in China and Jian Han, Faculty Investigator at the Hudson Alpha Institute in Alabama and founder of iRepertoire. Zhong is one of the doctors who first diagnosed SARS and was instrumental in treating and controlling the disease. Han was previously recognized for his work during the SARS outbreak, earning a Wall Street Journal Technology Innovation Award.

Now, Han, Zhong, and collaborators have taken insights from their experience with SARS and used them to take an unprecedented approach to studying COVID-19. For emerging viruses with no vaccine, our only defense is our immune system. This study provides an unprecedented level of insight into the immune cells of 23 COVID-19 patients over three different stages of the disease.

In order for our immune system to fight off a new infectious disease, it first has to learn to recognize it. That recognition is coordinated by a family of proteins called receptors that live on the surface of T cells and B cells.

There are seven types of T cell and B cell receptor proteins, called chains, two of which combine to form the receptors on the surface of each B or T cell. Each individual chain is made up of multiple different segments, enabling millions of different unique B and T cells in every person.

When a new infection is introduced, the immune cells that recognize the invading virus multiply rapidly, causing a shift in the diversity of B and or T cells. By studying an infected persons immune system fingerprint, known as the immune repertoire, we can gain insights into what kind of immune cells will be effective at fighting off the virus.

This study captured, for the first time, the expansion and contraction of all seven chains in the immune repertoire. They discovered that early in COVID-19 infection, T cell discovery is significantly depleted. T cells recovered as patients improved, suggesting that the T cell repertoire might be an important marker for predicting disease progression.

For B cells, the chain composition of receptors can indicate whether the B cell has become activated by an infection. Activated B cells switch their chain type (from D/M to A/M, or G/M) and begin producing antibodies. Determining which specific chains are activated might help identify what antibodies will be effective in treating the infection. Chen and colleagues discovered that patients infected with COVID-19 exhibit a prominent expansion of their M- and G-type chains, followed by a later transition to A-type chains.

The next step is to isolate individual B cells that are exhibiting chain switching in order to identify the antibodies produced by patients who recover from infection, said Han. We are continuing this work at iRepertoire by performing network analysis on the B-cell data from these patients and identifying responding clones. We are also participating in a local study to use our single cell sequencing technology on samples from infected patients by directly identifying Sars-Cov-2-specific B-cells. Both methods can reveal the identity of neutralizing antibodies of therapeutic value.

What really makes this study interesting, is that we profiled all seven chains of the immune repertoire at the same time, said Miranda Byrne-Steele, Director of Research and Development at iRepertoire and an author on the paper. Most studies look at one or two chains at a time. By profiling all seven chains, we identified patterns that you wouldnt have noticed in a single chain study.

Those patterns have potential clinical significance. For T-cells, the signature observed in patients that recover versus those that progress, could aid in the development of prognostic tests. Such tests might help identify which patients are likely to need or benefit from particular treatments. For B-cells, those that proliferate might point to antibodies that can themselves serve as potential treatments for people who are already infected, but not recovering.

Reference: Longitudinal Analysis of T and B Cell Receptor Repertoire Transcripts Reveal Dynamic Immune Response in COVID-19 Patients by Xuefeng Niu, Song Li, Pingchao Li, Wenjing Pan, Qian Wang, Ying Feng, Xiaoneng Mo, Qihong Yan, Xianmiao Ye, Jia Luo, Linbing Qu, Daniel Weber, Miranda L. Byrne-Steele, Zhe Wang, Fengjia Yu, Fang Li, Richard M. Myers, Michael T. Lotze, Nanshan Zhong, Jian Han and Ling Chen, 30 September 2020, Frontiers in Immunology.DOI: 10.3389/fimmu.2020.582010

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Immunology

Boehringer expands oncology partnership with Oxford BioTherapeutics – pharmaceutical-technology.com

Boehringer Ingelheim has announced the expansion of its partnership with UK-basedOxford BioTherapeutics (OBT) to discover novel selective targets for strategic cancer indications to deliver treatments for cancer patients.

Financial terms of the expanded deal remain undivulged.

Under the deal, Boehringer will develop and commercialise antibody product candidates that interact with the novel targets identified by OBTs OGAP platform.

OBT is eligible for development and regulatory milestone payments and royalties on any product sales in the future.

Boehringer will utilise the OGAP platform to discover targets for novel immunotherapies using its T-cell engager, cancer vaccine and oncolytic virus platforms.

The latest development follows the initiation of dosing in a Phase I trial of a bispecific antibody for treating small cell lung carcinoma patients and those with other neoplasms.

The target for the bispecific antibody was discovered during the first phase of the companies collaboration.

So far, Boehringer exercised two options under the first deal, picking two therapeutic candidates for further development.

Boehringer Ingelheim Cancer Immunology & Immune Modulation Research senior vice-president and global head Jonathon Sedgwick said: This collaboration with Oxford BioTherapeutics is important for advancing therapeutic modalities that depend upon the identification of unique and specific tumour antigens within our cancer immunology portfolio.

OBTs programmes enable discovery of new treatment targets and build antibodies specific to those targets including CAR-T, other T-cell and NK cell-mediated cytotoxicity (ADCC) treatments to address difficult-to-treat cancers.

Oxford BioTherapeutics CEO Christian Rohlff said: We view the hopeful discovery of additional tumour targets as further confirmation of the value of our OGAP platform to identify novel targets that can be substrates for innovative new therapies.

Last month, Boehringer partnered with Click Therapeuticsto develop and commercialise a new prescription digital therapeutic, CT-155, to treat schizophrenia.

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Immunology

COVID-19 Preventative Measures Associated With Reduced Asthma Hospitalizations – Benzinga

MILWAUKEE, Oct. 13, 2020 /PRNewswire-PRWeb/ --According to new research published in The Journal of Allergy and Clinical Immunology: In Practice (JACI: In Practice), preventative measures used to slow the spread of COVID-19 in Japan have also lowered the rate of hospitalizations for asthma.

Researchers used the Diagnosis Procedure Combination inpatient database to conduct their research. The data on all hospitalizations per week across 272 hospitals nationwide from December 30, 2019, to May 31, 2020, was gathered and compared to the same periods in 2017, 2018, and 2019.

A total of 16,317 hospitalizations for asthma were observed in the study. Asthma hospitalizations in 2017-2019 and 2020 showed parallel trends until week eight. Researchers observed a decline in asthma hospitalizations from week nine onwards in 2020. Hospitalizations for COVID-19 were first observed during week seven of 2020. Further analysis found the average number of asthma hospitalizations significantly decreased during weeks nine to 22 in 2020 compared to 2017-2019 for both children and adults.

"Asthma hospitalizations usually indicate that an individual's asthma is not currently under control," said Atsushi Miyawaki, MD, PhD, corresponding author for the study. "This would suggest that asthma control improved during the pandemic. It illustrates the importance of environmental factors when it comes to treating and managing patients with asthma."

One possible explanation for the results is that increased hygiene by individuals to reduce their chances of contracting COVID-19 would also reduce their exposure to asthma triggers. Enhanced preventative measures by individuals concerned that COVID-19 may trigger asthma, such as frequent cleaning and reduced smoking, may also have helped to remove allergen triggers. Individuals may have also been more likely to use preventative asthma medications. Another explanation might be that community prevention measures may have helped suppress other respiratory infections, which can cause asthma exacerbations.

You can learn more about asthma and COVID-19 on the American Academy of Allergy, Asthma & Immunology website, aaaai.org.

The American Academy of Allergy, Asthma & Immunology (AAAAI) represents allergists, asthma specialists, clinical immunologists, allied health professionals and others with a special interest in the research and treatment of allergic and immunologic diseases. Established in 1943, the AAAAI has more than 7,100 members in the United States, Canada and 72 other countries. The AAAAI's Find an Allergist/Immunologist service is a trusted resource to help you find a specialist close to home.

SOURCE The American Academy of Allergy, Asthma & Immunology

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Immunology

Daniela Weiskopf awarded $1.4 million to study COVID-19 in Latino Americans – Latino Americans have been hit very hard by the COVID-19 pandemic. In…

San Diego Community News Group

Dr. Daniela Weiskopf (Credit: Gina Kirchweger, La Jolla Institute for Immunology)

Latino Americans have been hit very hard by the COVID-19 pandemic. In fact, the U.S. Centers for Disease Control and Prevention have reported that Hispanic and Latino Americans have been hospitalized with COVID-19 at more than four times the rate of white Americans. This huge disparity can be linked to lower access to health insurance and health care, as well as a higher likelihood of exposure through essential jobs.

At the same time, researchers also want to know if Latino Americans may have immune system differences that sway how they respond to the SARS-CoV-2 virus.

Now La Jolla Institute for Immunology research assistant professor Daniela Weiskopf, Ph.D., has been granted $1.4 million from the National Institutes of Healths National Cancer Institute (NCI) to examine the immune response to SARS-CoV-2 in study volunteers from Puerto Rico, where at least 75 percent of the population identifies as Hispanic or Latino. The five-year project is part of NCIs Serological Sciences Network (SeroNet), the largest coordinated effort to study immunology and COVID-19 in the United States.

We know the Latino population is over-represented in terms of COVID-19 cases, says Weiskopf. We need to get the whole picture.

The nations top researchers in academia, government and private industry have come together in an unprecedented effort to fight the pandemic, says Dinah Singer, Ph.D., deputy director of NCI. Through SeroNet, we are examining the immune response to the coronavirus to speed delivery of testing, treatments and vaccine development for COVID-19. What we learn could be applied immediately and will prove invaluable to public health beyond the current pandemic.

Weiskopfs research focuses on how gene expression patterns affect how a person responds to a viral infection. An expert in mosquito-borne viruses, she pivoted to studying SARS-CoV-2 very early in the pandemic. Her study in the May issue of Cell, with LJI Professors Shane Crotty, Ph.D., and Alessandro Sette, Dr. Bio. Sci., offered the first detailed analysis of the human immune response to SARS-CoV-2. The research team has since published key T cell studies in Science, Science Immunology and Cell that could help guide COVID-19 vaccine development.

For the new project, Weiskopf will work closely with project co-leaders Carlos Sariol, M.D., of the University of Puerto Rico and Marcos Lpez-Casillas, Ph.D., of the University of Puerto Rico and the Puerto Rico Science, Technology and Research Trust. Weiskopf and her colleagues at LJI will analyze blood samples from patients in Puerto Rico to study how their T cells respond to the virus. Researchers at the Saint Louis University will then study the antibody response in these patients.

We will basically have the entire adaptive immune response covered, says Weiskopf. This work will also give us a baseline for how many people in the population have been exposed or have been infected and how they respond.

Weiskopf has worked with Sariols team at the University of Puerto Rico on previous studies of immune responses to dengue virus, Zika virus and other related viruses. This work is made possible through an island-wide clinical network that collects blood samples for scientific research.

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Daniela Weiskopf awarded $1.4 million to study COVID-19 in Latino Americans - Latino Americans have been hit very hard by the COVID-19 pandemic. In...

Immunology

Targeting the tumour stroma: Phenomic AI launches with $6m financing – pharmaceutical-technology.com

Toronto-headquartered Phenomic AI has launched with $6m in seed funding. The round was led by CTI Life Sciences Fund, while AV8 Ventures, Luminous Ventures, and Viva BioInnovator also joined the round.

Phenomic plans to use this funding to push our lead programs through in vivo proof-of-concept studies, explains CEO Sam Cooper. The companys two lead programmes were discovered using its artificial intelligence (AI) and machine learning (ML) platform and they are antibody drugs that target the tumour stroma, which has prevented immunotherapies, such as checkpoint inhibitors, working effectively in solid cancers.

Cooper adds the funds will allow us to continue building out our platform, identify additional drug targets to enrich our pipeline, and expand internal efforts and collaborations with top academic institutions around the world.

Founded in 2017, Phenomic initially focused on software, but the team quickly realised our AI/ML platform could be used to screen targets in complex assays that contain different cell types, and which previously presented a significant analysis challenge, notes Cooper.

CTI Life Sciences Fund managing partner Shermaine Tilley explained in a statement: Cells do not exist in isolation in the human body, and the interactions between different cell types in disease states carries significant information that Phenomic has unlocked for drug discovery.

As a result, Phenomic could overcome the challenges involved in understanding how different cells interact in disease states and particularly tumour stroma of solid cancers, a major unsolved puzzle in cancer, in the words of Cooper.

The tumour stroma is a very complex barrier to the tumour, which is comprised of many cell types, such as the extracellular matrix and cancer-associated fibroblasts (CAFs) and it is a major barrier that prevents checkpoint therapies from working effectively, explains Cooper. Checkpoint inhibitors have been a recent revolution in the treatment of cancers, but solid tumours have been excluded from its benefit because of the tumour stroma.

By targeting the tumour stroma effectively with therapeutic antibodies, we aim to activate the immune system in stroma-rich cancers, either directly or in combination with immune checkpoint therapies, says Cooper.

Phenomics drugs target CAFs in numerous solid cancers, including colorectal cancer, because analysis suggests these targets are playing a critical role in promoting tumour growth and blocking anti-tumour immune activity.

To coincide with the seed round, Phenomic has appointed chief scientific officer Dr Mike Briskin and two Nobel laureates Jim Allison and Pam Sharma to its scientific advisory board.

AV8 general partner Ruchita Sinha commented: In two years, the Phenomic team has made impressive progress in building their platform and using it to find new drug targets in the tumour stroma. The appointments of Mike, Jim, and Pam, leaders in immuno-oncology, further highlight the exceptional advancements of Phenomic.

Cooper adds: Mikes experience as a serial biotech entrepreneur and his expertise in immuno-oncology is an important addition to the team, and one that will help further our goals of getting exceptional medicines into the clinic and ultimately approved for the benefit of patients.

Jim and Pam are undoubtedly two of the best immunologists alive today, having brought to light field-defining discoveries in cancer immunology. Their guidance and knowledge have put us in a world-leading position with insights and knowledge needed to effectively solve the stromal puzzle.

Were unbelievably happy to have them team up with Phenomic and bring their expertise, and the work that theyve put into this problem to date, to the company.

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Immunology

What we know about COVID-19 and immunity – PolitiFact

Since his return from Walter Reed National Military Medical Center, President Donald Trump has repeated that he may now be "immune" to the coronavirus. In a video released shortly after he arrived back at the White House, he said, "Now Im better, and maybe Im immune, I dont know."

In a 55-minute interview on Fox Business, he made several claims about his health and COVID-19 immunity, saying, "When you catch it you get better, and then youre immune," and jokingly referred to himself as a "perfect physical specimen."

But medical experts say there are still a lot of unknowns about COVID-19 immunity.

Do all recovered COVID-19 patients become immune, regardless of the severity? For how long? Will the virus behave like the flu, requiring a vaccine each year? How do we achieve herd immunity?

We spoke with immunology and infectious disease experts about what they have learned and still dont know about COVID-19 and immunity.

Heres what we found out.

How does COVID-19 immunity work?

A person achieves immunity to a disease when the bodys immune system has fought off the virus once and is now strengthened to resist further attack. The immune system has a kind of memory for previous pathogens, allowing the body to have a quicker, stronger response the next time it encounters a past invader.

This can happen naturally or via vaccine.

Medical experts say its hard to know for certain the strength and length of immunity for recovering COVID-19 patients, because its a new virus and not enough studies have been done. However, there are indicators that suggest there is some natural protection against the disease post-recovery.

The biggest clue is that recovered patients rarely get reinfected with COVID-19, experts said, especially when considering the huge number of people who have been infected with the virus around the world.

"The very high-level picture is pretty stable," said Dr. Sarah Fortune, chair of the Immunology and Infectious Diseases department at Harvard T.H. Chan School of Public Health.

"Both the clinical data and the animal studies suggest that there is meaningful protection against disease," Fortune said. "Its not as if youre seeing rampant recurrent infections with recurrent severe symptoms. Its not as if there are no cases, but by and large you're seeing substantial protection against disease."

Experts also said previous studies that looked at common cold coronaviruses showed that people develop immunity for extended periods of time (at least a year), though it varied slightly from case to case.

There may be some differences in the level of immunity for those who had a serious infection, versus those who only experienced mild symptoms, researchers say. Generally, patients who dealt with a severe infection are likely going to have a higher antibody count.

"But that doesnt mean that your mild infection isn't providing you enough immunity to protect you against the disease," Fortune said. "Even if its lower, it appears to be completely proficient in protecting you against the disease. And, in most of the people who are infected, they develop a mild case and we arent seeing many reinfections."

How long does immunity to COVID-19 last?

Theres no standard time frame for immunity after someone recovers from COVID-19. Different public health groups have different estimates, with the most conservative being about four months

Researchers say its likely that people are immune for longer, but note that with a rapidly spreading disease that has no cure, people should keep their guard up rather than return to life as normal and put themselves and others at risk.

One common misconception immunologists raised is the public perception of immunity in general, with many people thinking youre either immune or youre not. Thats not how it works.

"Protection is not like a light switch, its like a dimmer switch," Fortune said. "You will be more protected in the beginning, and over time that protection might wane, but its not going to just go away.

For example, as a persons immunity wanes, they may eventually get infected from the virus again, but not actually get sick. Or even further out, they may get infected and then have mild symptoms but nothing severe.

The takeaway: The loss of immunity is gradual, not drastic.

Will we have to get multiple vaccines for COVID-19, like the flu?

The flu is a respiratory virus like the coronavirus, but its also quite different. The flu rapidly shifts and mutates, making it more resistant to long-term immunity. Thats why there is a new vaccine each year.

If the virus that causes COVID-19 continues to behave like other coronaviruses, people will likely have more stable immunity from a limited vaccination schedule.

"There's no evidence, so far, that people will need to be vaccinated each year because of the virus mutating," said Dr. Stanley Perlman, a professor of microbiology and immunology at the University of Iowa. "That may be because of their immunity waning, but not because the virus is changing."

Fortune agreed. "Theres no evidence that Sars-Cov-2 (the virus that causes COVID-19) is going to, or has undergone, a really dramatic re-shuffling that makes it escape either a natural immunity or even a vaccine-induced immunity," she said. "That's not to say that its not possible there wont be a new one in the future, but just that the virus doesn't share the same characteristics of the seasonal, whole-scale remaking of itself that the flu does."

Does a positive antibody test mean a person is immune?

Positive test results dont guarantee immunity. The presence of antibodies only means that the person has been exposed to the virus in the past.

How sensitive, or how "good," the antibody test is, and the amount of antibodies a person has, weighs heavily on whether or not they would be considered immune from the virus.

The same thing is true with a PCR diagnostic COVID-19 test.

"Some people have very positive PCR tests and thats more of a worry than someone with fluctuating PCR tests negative one day, positive the next because they have less of a viral load," Perlman said. "Its the same thing with antibodies. You can test positive for antibodies but have so little that it doesnt really protect you, or you can have a high number of antibodies, which means youre better protected. The amount matters."

What about herd immunity?

Herd immunity is the idea that when enough people in a population are immune, either by having the infection or receiving a vaccine, the virus will have trouble spreading. Thats because an infected person is less likely to encounter a non-immune person to pass it on to, making them a dead-end in the chain of transmission.

When that happens enough times on a large scale, it drives its rate down and eventually gets the disease under control, but it doesnt necessarily eradicate it.

RELATED: Corralling the facts on herd immunity

The U.S. is still considered far from adequate COVID-19 herd immunity, and experts say there would have to be many more cases and deaths before we get there if a vaccine doesnt arrive first. Fewer than 1 in 10 Americans show signs of past infection as of late July, according to a Sept. 25 study published in The Lancet journal.

So, experts agree that the ideal way to achieve herd immunity is with a vaccine. While some immunity within a population is better than none, with a virus that spreads through the air, the higher the number of people who are immune, the better.

Different numbers have been tossed around by scientists on just how much of the population needs to be immune in order for herd immunity to work well. The mathematical model for Sars-Cov-2 which is derived based on the virus transmission characteristics and on how the population behaves puts it around 60-70 people out of every 100.

For the most highly contagious diseases, like measles, scientists say about 94% of the population needs to be immunized to achieve that level of protection.

"That doesn't mean that it goes away when we reach herd immunity, it just means that you're not propagating the epidemic," Fortune said. "People should have that in mind with herd immunity, and with the future, it's not like one day, we achieved herd immunity and its gone."

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What we know about COVID-19 and immunity - PolitiFact

Immunology

An Autoimmune-Like Antibody Response Has Been Linked With Severe COVID-19 – ScienceAlert

In the earliest days of the pandemic, many immunologists, including me, assumed that patients who produced high quantities of antibodies early in infection would be free from disease. We were wrong.

Several months into studying COVID-19, like other scientists, I've come to realize the picture is far more complicated. A recent research study published by my colleagues and me adds more evidence to the idea that in some patients, preventing dysregulated immune system responses may be as important as treating the virus itself.

I am an immunologist at Emory University working under the direction of Dr. Ignacio Sanz, Emory's chief of rheumatology. Immune dysregulation is our specialty.

A harrowing turn in the COVID-19 pandemic occurred with the realization that the immune system's power in fighting infection was sometimes pyrrhic.

In patients with severe COVID-19 infections, evidence emerged that the inflammatory process used to fight the SARS-CoV-2 virus were, in addition to fighting the virus, potentially responsible for harming the patient.

Clinical studies described so-called cytokine storms in which the immune system produced an overwhelming quantity of inflammatory molecules, antibodies triggering dangerous blood clots and inflammation of multiple organ systems, including blood vessels, in COVID-recovered children. All these were warning signs that in some patients, immune responses to the SARS-CoV-2 virus, which causes COVID-19, may have tipped from healing to destructive.

Quick thinking and courageous decisions made by physicians on the front lines led to the use of steroids, medicines that dampen the immune response, early on in the course of infection of hospitalized patients. This approach has saved lives.

But it's not yet clear what parts of the immune system physicians are dampening that is having the effect. Understanding the nature of immune dysregulation in COVID-19 could help identify patients in whom these treatments are most effective. It may even justify more targeted and powerful approaches for modulating the immune system currently reserved for autoimmune diseases.

Antibodies are powerful weapons. Produced by white blood cells called B cells, they latch onto infectious agents like viruses and bacteria and prevent them from infecting your healthy cells. These antibody-virus aggregates unleash powerful inflammatory reactions and serve as homing beacons that allow the rest of your immune system to target the pathogens efficiently. In some circumstances, they can even kill.

Antibodies are so powerful that cases of mistaken identity when a B cell produces antibodies that attack a person's own cells can lead to widespread organ damage and establish a perpetual cycle of immune self-targeting. We refer to this state of self-destruction as an autoimmune disease.

To avoid autoimmune disaster, and to ensure effective response against the invading pathogen, B cells undergo a training process. Those that respond to the virus refine their antibodies and mature, ensuring potent antibodies capable of disabling the invader. B cells that target your own tissue are destroyed.

But that maturation process takes time. Two weeks of B cell "training" during a severe infection can mean the difference between life and death. Faster antibody responses are needed.

To bridge that gap, the immune system has an alternative form of B cell activation called extrafollicular activation that generates fast-acting antibodies that seem to bypass many of the known safety checks that accompany a more precise response.

Extrafollicular responses develop quickly, are short-lived by design and die back when the more targeted responses emerge onto the scene.

Except when they don't.

Between 2015 and 2018, our lab found that these extrafollicular immune system responses were a common characteristic of people who suffered from autoimmune diseases, such as lupus.

Patients suffering from this disease show chronically active extrafollicular responses that led to high levels of self-targeted antibodies and destruction of organs such as the lungs, heart and kidneys.

The presence of specific kinds of B cells generated by extrafollicular responses in the blood can be an important indicator of disease severity in lupus, and now also COVID-19.

In a recently published paper, my colleagues and I have identified extrafollicular B cell signatures in cases of severe COVID-19 similar to those we saw in active lupus. We showed that early on in the response to infection, patients with severe disease undergo a rapid activation of this fast-track pathway for antibody production.

These patients produce high levels of viral-specific antibodies, some which are capable of neutralizing the virus. However, in addition to those protective antibodies, some that we saw look suspiciously like the ones found in autoimmune disorders such lupus.

In the end, patients with these autoimmune-like B cell responses fare poorly, with high incidences of systemic organ failure and death.

Let me be clear here: COVID-19 is not an autoimmune disorder. The autoimmune-like inflammatory responses my team discovered could simply reflect a "normal" response to a viral infection already out of hand.

However, even if this kind of response is 'normal', it doesn't mean that it's not dangerous. These prolonged extrafollicular responses have been shown to contribute to autoimmune disease severity both through the production of self-targeted antibodies and through inflammation that can damage tissue like the lung and kidney.

This suggests that these early immune responses to a viral infection like COVID-19 are in tension with the later-targeted antibody response; in other words, the body's rapid antibody production to nab the virus runs the risk of targeting not the virus, but the patient's own organs and tissues.

Immunologists like me need to learn more. Why are only some patients turning on such strong extrafollicular B cell responses? Are the antibodies that result from this response particularly prone to attacking and destroying the host's organs? Would an ongoing autoreactive response help explain instances of "lingering" COVID-19 even after the viral infection has cleared?

Despite these uncertainties, the medical community needs to recognize that, in the appropriate patients, dampening immune responses through steroid treatment (or perhaps even more powerful autoimmune-focused therapies) is a critical weapon in combating COVID-19.

Physicians and scientists must continue to build our arsenal of therapeutics around the idea that in some cases of COVID-19, controlling your response to the virus might be as important as controlling the virus itself.

Matthew Woodruff, Instructor, Lowance Center for Human Immunology, Emory University.

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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An Autoimmune-Like Antibody Response Has Been Linked With Severe COVID-19 - ScienceAlert

Immunology

Nature Publishes New Research from Vir Biotechnology Demonstrating the Capacity of Enhanced Monoclonal Antibodies to Induce Protective Adaptive…

SAN FRANCISCO, Oct. 09, 2020 (GLOBE NEWSWIRE) -- Vir Biotechnology Inc. (Nasdaq: VIR) today announced the publication of preclinical research in an influenza animal model highlighting a new mechanism for enhancing the efficacy of monoclonal antibodies to treat viral infection and induce a protective response. Data demonstrate that selective engagement of an activating Fc receptor on dendritic cells by antiviral monoclonal antibodies induced protective CD8+ T cell adaptive responses. The paper, entitled Fc-optimized antibodies elicit CD8 immunity to viral respiratory infection, was published in the October 8, 2020 online edition of Nature.

In the past several years, we've gained a better understanding of how integral Fc mediated effector functions of monoclonal antibodies are for their therapeutic efficacy in pre-clinical models of neoplastic, infectious and inflammatory diseases, said Jeffrey V. Ravetch, M.D., Ph.D., study senior author and Theresa and Eugene M. Lang Professor and Head of the Leonard Wagner Laboratory of Molecular Genetics and Immunology at The Rockefeller University. These approaches have been successfully applied to anti-tumor therapeutics and have resulted in improved clinical outcomes in a variety of oncologic diseases. Our present studies have uncovered a significant new mechanism by which antibodies, through their Fc region, can not only engage innate immune responses but activate adaptive T cell responses, thereby stimulating protective anti-viral immunity in these models.

The research published in Nature focuses on the role of the Fc domain of monoclonal antibodies, regions with the capacity to bind to other immune cells through a family of receptors (the Fc receptors). By engineering antibodies with modified Fc domains to enhance binding to specific Fc receptors on innate immune cells, investigators observed an enhanced protective immune response. Certain modifications (GAALIE variants) were associated with activation of dendritic cells, as well as antiviral effector T-cells, indicating induction of the adaptive arm of the immune system, which is responsible for long-term immunity. Based on this research, monoclonal antibodies programmed with improved effector function represent a potential new approach in the design of therapeutic antibodies for both the prevention and treatment of infectious diseases.

By observing and learning from our bodys powerful natural defenses, we have discovered how to maximize the capacity of antibodies through the amplification of key characteristics that may enable more effective treatments for viral diseases, said Herbert Skip Virgin, M.D., Ph.D., study co-author and executive vice president, research, and chief scientific officer of Vir. These data may have significant implications across a wide range of infectious diseases, and we look forward to exploring the vaccinal potential of the GAALIE-engineered antibodies we are advancing through clinical development VIR-3434 for chronic hepatitis B and VIR-7832 for SARS-CoV-2.

The preclinical study was conducted by Dr. Ravetch and Stylianos Bournazos, Ph.D., of the Laboratory of Molecular Genetics and Immunology at The Rockefeller University, in collaboration with Dr. Virgin and Davide Corti, Ph.D., senior vice president of antibody research at Virs subsidiary Humabs BioMed SA.

This type of exceptional collaborative partnership between cutting-edge science and clinical application has the potential to significantly improve our ability to address infectious diseases, stated Dr. Virgin.

Vir is currently evaluating several monoclonal antibodies that have been Fc engineered to include the XX2 vaccinal mutation (or GAALIE variant) for which Vir has licensed exclusive rights for all infectious diseases.

About VIR-3434VIR-3434 is a subcutaneously administered HBV-neutralizing monoclonal antibody designed to block entry of all 10 genotypes of HBV into hepatocytes and also to reduce the level of virions and subviral particles in the blood. VIR-3434 has been engineered to have an extended half-life as well as to potentially function as a T cell vaccine against HBV in infected patients.

About VIR-7832VIR-7832 is a monoclonal antibody that has shown the ability to neutralize SARS-CoV-2 live virus in vitro. The antibody binds to an epitope on SARS-CoV-2 that is shared with SARS-CoV-1 (also known as SARS), indicating that the epitope is highly conserved, which may make it more difficult for escape mutants to develop. VIR-7832 has been engineered with the potential to enhance lung bioavailability, have an extended half-life, and function as a therapeutic and/or prophylactic T cell vaccine. VIR-7832 is being developed by Vir and its partner GlaxoSmithKline plc(LSE/NYSE: GSK) as part of their broader collaboration to research and develop solutions for coronaviruses, including SARS-CoV-2.

About Vir BiotechnologyVir Biotechnology is a clinical-stage immunology company focused on combining immunologic insights with cutting-edge technologies to treat and prevent serious infectious diseases. Vir has assembled four technology platforms that are designed to stimulate and enhance the immune system by exploiting critical observations of natural immune processes. Its current development pipeline consists of product candidates targeting hepatitis B virus, influenza A, SARS-CoV-2, human immunodeficiency virus and tuberculosis. For more information, please visitwww.vir.bio.

Vir Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as potential, may, will, could, expect, plan, anticipate, believe, estimate, goal, intend, candidate, continuing, developing and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. These forward-looking statements are based on Virs expectations and assumptions as of the date of this press release. Each of these forward-looking statements involves risks and uncertainties. Actual results may differ materially from these forward-looking statements. Forward-looking statements contained in this press release include statements regarding the ability of enhanced Fc mediated effector functions in enhancing the efficacy of monoclonal antibodies to treat viral infections and inducing a protective response in animal models, using an oncological therapeutic approach and enhanced effector function in the treatment of infectious diseases, the vaccinal potential of specifically engineered antibodies in the treatment of chronic hepatitis B and SARS-CoV-2, and statements around the companys plans to explore the vaccinal potential of engineered antibodies as it advances through clinical development of VIR-3434 for the treatment of chronic hepatitis B and VIR-7832 for SARS-CoV-2. Many factors may cause differences between current expectations and actual results including unexpected safety or efficacy data observed during preclinical or clinical studies, challenges in treating chronic hepatitis B and neutralizing SARS-CoV-2, difficulty in collaborating with other companies or government agencies, and challenges in accessing manufacturing capacity. Other factors that may cause actual results to differ from those expressed or implied in the forward-looking statements in this press release are discussed in Virs filings with theU.S. Securities and Exchange Commission, including the section titled Risk Factors contained therein. Except as required by law, Vir assumes no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available.

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Nature Publishes New Research from Vir Biotechnology Demonstrating the Capacity of Enhanced Monoclonal Antibodies to Induce Protective Adaptive...