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The Academy Lights Israel Up

University and college buildings across the country were illuminated in the colors of the Israeli flag this evening:

University and college buildings across the country, from Tel Hai in the North, to Sapir in the South, were illuminated in the colors of the Israeli flag this evening (Tuesday) at 7:30 p.m., in an effort to show support for the security and rescue forces, as well as all citizens and residents of the State of Israel, which is undergoing a continuous war.

At Tel Aviv University, our national pride was on display as the campus was adorned with iconic symbols. The “Broshim” dormitory now showcases a large illuminated Israeli flag, while the windows of the Broadcom Building, home to the advanced research and development center for the Faculty of Engineering and Broadcom company, were meticulously lit to form the distinct outline of the Israeli flag. Positioned prominently along the Ayalon highway, these illuminated structures served as a proud testament to the university’s commitment to its national identity, catching the eye of every passing driver.

According to the initiative’s organizers, “Our hearts go out to the families of those who have been brutally murdered, wounded, kidnapped, captured, and those still missing.”

There are many faculty members and students who have been called up for military service, with the entire country being mobilized and taking part in fighting or strengthening the Home Front.

Educational institutions want to make sure they know we are always behind them, thinking of and worrying about them, and we are praying for their safe return home!

“May this light illuminate your path and inspire hope among all of Israel.”

One of the buildings of  Broshim Student Dormitories

 

A Letter from VERA – Association of University Heads, Israel

“We all share the responsibility to educate our communities.”

To our colleagues, heads of universities around the world,

These are difficult times. We thank you for the support and concern we have already received from so many of you.

As you are aware, early last Saturday morning, Hamas carried out an unusually brutal and violent attack primarily against civilians, within Israel. While the leadership of some academic institutions has issued public condemnations, we learned that in others this has been regarded as just “one more event” in the ongoing conflict between Israelis and Palestinians, which can be understood from multiple perspectives.

We would like to emphasize that this is far from the truth.  This was an act of singular barbaric violence which must be thoroughly renounced.  To show why this is so, we will need to share some truly disturbing details, as referred to in President Biden’s speech and now coming to light in the international press. We know that these will disturb you no less than they have shaken us.

On the Sabbath and Sukkoth holiday and 50 years almost to the day after the fateful Yom Kippur War, Hamas unleashed a surprise rocket attack on Israel from Gaza, reaching as far north as the Tel Aviv and Jerusalem areas, while simultaneously Hamas and Islamic Jihad militants breached the border and brutally massacred those in the communities just across the border inside Israel – women, elderly, children, young families. Kids attending a music festival, peace activists, elderly people in their 80’s, toddlers.  Hundreds. Many were slaughtered on the spot, others huddled in their homes for hours before being found and killed or were held hostage in their homes or communities under constant threat of death, while still others were taken captive and brought into Gaza. Horrific videos posted by Hamas from Gaza show the parading of injured hostages in the street to great cheering, show cruelty to children, taunting of the elderly, show rape and torture.

All this as hundreds of Israelis were injured or killed by indiscriminate rocket fire, which has hit both Jewish towns and Bedouin and Arab villages.  Just two days ago, a mosque in the village of Abu Ghosh was hit by rocket fire.

Let’s be clear.  This is not “war as usual” or just another chapter in the Israeli-Palestinian conflict.  There are not “good people on both sides”.  Hamas and Islamic Jihad have proven themselves to be cruel, barbaric organizations reminiscent of the Taliban and the Islamic State.

We have heard of initiatives undertaken by faculty and students on some campuses in countries outside of Israel to support Hamas and Islamic Jihad actions, and we understand that there has not always been a clear response from academic leadership to such signs of support. We hope that you will agree with us that there can be no support for such terror organizations in Western democratic societies, just like there is no support for Al Qaeda or the Islamic State. There can be no support for purposeful massacres of civilian populations, or for the taking civilian hostages.

As the guardians of higher education and academia, actively pursuing knowledge for the benefit of humanity, as role models for and teachers of the leadership of tomorrow, we all share the responsibility to educate our communities.

What values are we passing on? Freedom of speech and academic freedom, absolutely.  But a stand against barbaric violence perpetrated on civilian populations?  We know you join us in renouncing such acts of violence.

Yours,

Prof. Arie Zaban, President, Bar-Ilan University; Chairperson – Association of University Heads – VERA

Prof. Daniel A. Chamovitz, President, Ben-Gurion University of the Negev

Prof. Alon Chen, President, Weizmann Institute of Science

Prof. Asher Cohen, President, the Hebrew University of Jerusalem

Prof. Leo Corry, President, the Open University of Israel

Prof. Ehud Grossman, President, Ariel University

Prof. Ariel Porat, President, Tel-Aviv University

Prof. Ron Robin, President, University of Haifa

Prof. Uri Sivan, President, the Technion-Israel Institute of Technology

War in Israel – New Update from the TAU President

Dear faculty, staff, and students, 

Let me begin by expressing deep, almost unbearable sorrow for the death of over 1,200 women, men, and children, murdered or killed in the horrific crime perpetrated against the Jewish people in its homeland. I am immensely grieved by the death of 11 of our students and relatives of our faculty members, who have been murdered or killed in this atrocious attack. Their names can be found in this link which, sadly, we are updating as information flows in.

May their memory be blessed.  

Almost a week has gone by since the brutal massacre, and the enormous emotional burden grows heavier every day. We are burying our dead; we are exposed to more and more atrocities; we were devastated to discover that even small infants were not spared from the slaughter; and we are desperately concerned for the fate of the hostages. Indeed, such personal torment and nationwide anguish we have never known in the state of Israel, and the end is nowhere in sight.  

TAU has harnessed all its strength and abilities to support the nationwide efforts. We have established an emergency fund to provide financial assistance, and considerably reinforced the psychological services offered to the TAU community, including opening hotlines in both Hebrew and English. Our faculties and schools are personally contacting students who live in southern Israel or serve in the armed forces. We are hosting families of our students from the south in the TAU dorms. 

Together with the Student Union, TAU is recruiting volunteers from the TAU community, to help wherever help is needed. We are extremely proud of our Student Union, who are collecting food, clothing, medical equipment, and other necessities for mobilized soldiers and residents of southern Israel who have become refugees in their own land. In the coming days we will look for faculty members who can offer assistance in their own areas of expertise – such as social work, dentistry, various fields of medicine, psychology, law, etc. In fact, volunteer activities have already begun in the Schools of Dentistry and Social Work. We are turning to faculty, staff, and students, to ask whether they wish to host Israelis from the south in their own homes.  

But while we hurt and grieve, as individuals and as a nation, there are those who applaud the bloodshed. In places around the world, including the campuses of some renowned universities, we witness rising BDS activities, justifying the atrocities perpetrated by the butchers of Hamas. It is very hard to read or watch these posts in the social networks. It is hard to observe the feebleness of certain leaders of academic institutions, who do not do enough to prevent this abuse of freedom of speech. Freedom of speech is not an absolute right. It must be trumped by the sanctity of life and the value of personal safety. It cannot protect expressions of hatred or incitement to murder and violence. I would expect my colleagues, heads of academic institutions, especially in the USA, to treat students and personnel who justify the slaughter as they would have treated anyone who justified the events of 9/11. I would expect them to condemn–clearly, firmly, and unequivocally–the horrendous massacre that has taken place in our land. Some have done so. But others have not.  

Against this background, TAU is adding media outreach to its tasks. Some of our international students are already doing very valuable work in this respect. With the help of our Student Union, we are recruiting students who will operate in the social networks, to refute the terrible lies that might influence naïve, unknowing audiences who are unaware of what our enemy has done to us.  

Finally, I must speak of expressions of hatred and incitement right here on campus. A few of our students have expressed support for the atrocities of Hamas. Their number is very small, but that detracts nothing from the gravity of this phenomenon. We will be very strict with this handful of students, and when we feel the offense is criminal in nature, we shall report them to the police. We will act swiftly, as required in this sensitive situation, but will not deny any student the right to a fair investigation of the facts. A society is tested in its difficult hours – and none are more difficult than those we are experiencing today. Democracy and human rights are not to be suspended in wartime. If anything, their importance increases.   

At the same time, we are seeing deplorable incitement from extremists against our own students, whose only fault is being Arab. The Hamas murderers made no distinction between Jews and Arabs, and in their despicable attack many Arab Israelis were also killed and injured. The phenomenon of incitement against Arabs on our campus is of small proportions, but it shall not be overlooked. Inciters of any kind will not be tolerated. As noted above, a society is tested in its hour of calamity. TAU will serve as a model in this matter as well.  

I wish you all better days.  

Yours, 

Ariel Porat 

Tel Aviv University Commemorates the Fallen Members of Our University Community

TAU mourns with and shares the sorrow of the families who have lost loved ones in Operation Iron Swords

 

Roy Negri, a computer science and management student 

Roee Negri, a computer science and management student

 

Yuval Ben Yakov, son of Dr. Haim Ben Yakov 

Yuval Ben Yakov, son of Dr. Haim Ben Yakov, From the Department for Foreign Relations

 

Dan Ariel, son of Prof. Meir Ariel

Dan Ariel, son of Prof. Meir Ariel

 

Omri Belkin, Law student

Omri Belkin, Law student

 

Bruna Valeanu, a communication and sociology student

Bruna Valeanu, a communication and sociology student 

 

 Amnon Bezalel, father of Liat Bezalel, MA student in computer science

 Amnon Bezalel, father of Liat Bezalel, a graduate student in computer science, and Sapir Rivka Bezalel, a computer science student

 

Yahav Winner, husband of film and television student Shai Lee Atari

Yahav Winner, husband of film and television student Shai Lee Atari

 

Nitai Amar, son of Revital Amar, a master's student in social work

Nitai Amar, son of Revital Amar, a master’s student in social work

 

Tzur Tzaidi, Mia Tzaidi's brother, a student in the completion program for social work

Tzur Tzaidi, Mia Tzaidi’s brother, a student in the completion program for social work

 

Major Eliran Abarjil, Eden Ben Lulu's partner, a master's student in social work

Major Eliran Abarjil, Eden Ben Lulu’s partner, a master’s student in social work

 

Elhanan Clemanzon, Uri Clemanzon's brother, student for a degree in biology and psychology

Elhanan Clemanzon, Uri Clemanzon’s brother, student for a degree in biology and psychology

 

Sapir Rivka Bezalel, computer science student

Sapir Rivka Bezalel, computer science student

War in Israel – An Update from the TAU President

Tel Aviv University addresses the current situation.

My dear Governors, Friends, Alumni, and other members of the Tel Aviv University community in Israel and around the world, 

As I write these lines, the media is reporting that over 700 individuals have tragically lost their lives in the horrendous terror attack on the State of Israel. Unfortunately, it seems this number may rise. Reports suggest over 100 people have been taken captive, and even here, the number is not final. 

It is hard to describe the magnitude of the pain each and every one of us is experiencing these days. The images of grandparents kidnapped with their grandchildren, of a father left without his wife and children, of young children witnessing the murder of their parents – these pictures remind us of other bloody events in our people’s history. The determination to respond is stronger than ever, mixed with shock, tears and agonizing sorrow. Today, we are all united in our resolve that such an event should never happen again. 

We suspect there are victims from our university community, although it is still difficult to assess their number. The Dean for Student Success is working with the faculties and schools to establish contact with students and faculty members living in Israel’s South, or serving in the IDF and other security forces. TAU, along with the other universities in Israel, is postponing the start of the academic year by at least a week. We are significantly expanding the scope of psychological services we provide to the university community. TAU is also exploring ways to assist families from the south of the country, both with psychological counseling and with finding alternative housing until the war concludes. 

In recent days, many of our supporters and others have reached out to me to express their terrible grief and participation in our sorrow. We feel deeply that all of you are with us. We are one family. I hope that the war in which we find ourselves will end quickly and that calm will return. We do not cease to think about the Israeli hostages being held by the enemy. This situation is very distressing. We pray for their well-being. 

The State of Israel is the home of the Jewish people, not only for those who live in it. Your support during this difficult time is more important to us than ever. 

Yours sincerely, 

Ariel Porat 

Impact of the Constitutional Overhaul on National Resilience in Israel

Rise in national resilience of coalition supporters vs. steep decline among supporters of the opposition.

A joint study by researchers from Tel Aviv University and the Tel-Hai Academic College demonstrates scientifically what we have all noted in the media, in the social networks, and in the streets: while the national resilience of coalition supporters has risen significantly over the past year (from 3.5 to 3.9 on a scale of 1-6), the opposite is true for supporters of the opposition, who exhibited a steep decline in the index of national resilience (from 3.7 in October 2022 to 3.2 in August 2023).

The study was led by Prof. Shaul Kimhi, Prof. Bruria Adini, Dr. Maya Siman-Tov, and Arielle Kaim from the Department of Emergency and Disaster Management, School of Public Health, at Tel Aviv University, and Prof. Yohanan Eshel and Dr. Hadas Marciano from the Tel-Hai College and the University of Haifa.

The researchers explain that the study is based on three surveys within the same sample of Jewish Israelis (N=785): the first a short time before the last elections (October 2022), the second in February 2023, about three and a half months after the elections, in the midst of the constitutional overhaul, and the third at the beginning of August 2023. The study examined a range of parameters related to resilience, stress, and well-being: national resilience, personal resilience, hope, morale, distress symptoms, and sense of danger. Average national resilience scores among supporters of the current coalition indicate a statistically significant rise from 3.53 in the first survey to 3.85 in the third, while supporters of the present opposition showed a significant decline from 3.66 in the first to 3.20 in the third measurement. It should be noted that in the first survey supporters of the current opposition (who were then supporters of the ruling government) reported significantly higher national resilience compared to coalition supporters.

Illustration: Comparison between coalition and opposition supporters through 3 assessments of national resilience:

In the parameter of hope for a better future, the study indicates no statistically significant change in the average score of the whole sample between the first (3.53) and second (3.52) surveys. In the third survey, however, a steep decline was observed in the overall score – down to 3.17. At the same time, findings indicate a large gap between opposition and coalition supporters: while coalition supporters maintained a relatively high level of hope in all three surveys (3.6), hope among supporters of the opposition dropped from 3.4 to 2.8 (measured on a scale of 1-5).

“The findings arouse deep concern for our ability to deal with the multitude of threats facing us and pose a danger to our existence as a healthy and cohesive society”.

The parameter of personal resilience further demonstrates the impact of the constitutional overhaul on the Israeli public. The study’s findings indicate a sharp decline in the overall score through all three surveys – from 3.9 to 3.5 (scale of 1-5). This substantial decline in personal resilience levels was observed in both groups (coalition and opposition supporters), with no significant difference throughout the three surveys. In other words, all participants reported a decrease in their personal resilience.

As to the sense of danger parameter, as expected, supporters of the opposition reported that they felt a real threat to themselves and to the state, and their apprehension was expressed in a sharp rise (from 2.3 to 2.9). Coalition supporters, on the other hand, felt much safer, and this was expressed in a decrease (from 2.6 to 2.1) on a scale of 1-5.

From their findings, the researchers conclude that since the elections of November 2022, the gap between the two groups representing Israel’s Jewish population – coalition and opposition supporters – has increased constantly. In all parameters measured in the study it is apparent that following the elections and ensuing events, supporters of the opposition reported a significant drop in resilience measures – national resilience, personal resilience, hope for a better future, and morale, coupled with a rise in distress symptoms and the sense of danger. In addition, findings indicate that following the elections, the gap between the two groups has deepened, which leads to further exacerbation of the severe political/social crisis in which Israel finds itself today.

Prof. Bruria Adini added: “Studies have shown that the national (societal) resilience index is a good predictor of a society’s capacity to withstand varied crises. The current study presents rapidly growing rifts and a continually decreasing level of resilience in Israeli society. The findings arouse deep concern for our ability to deal with the multitude of threats facing us, and pose a danger to our existence as a healthy and cohesive society”.

Tel Aviv University ranked first outside the USA in the number of unicorns established by alumni

The Prestigious Stanford index ranks TAU as Israel’s leading entrepreneurial university.

A new study from Stanford University ranks Tel Aviv University first in Israel and first in the world outside the USA in the number of unicorns (privately held startup companies valued at over US$1 billion) established by its alumni. According to the study, led by entrepreneurship researcher Prof. Ilya Strebulaev from the Stanford Graduate School of Business, Stanford University is first in the world in the number of unicorns founded by its alumni and Tel Aviv University is first outside of the USA with 43 unicorns. The ranking, counting the total number of unicorns regardless of university size, is based on a dataset of 1,100 startups that have raised over $1 billion from venture capital funds in the USA.

“Prof. Strebulaev’s findings prove once again that TAU is Israel’s entrepreneurial university, nurturing more startups, and specifically more unicorns, than any other university in the country,” says Prof. Moshe Zviran, Chief Entrepreneurship & Innovation Officer at TAU, and former Dean of the Coller School of Management. “We have attained this status because we serve as home to the best students in a wide range of disciplines, and also because in recent years, under the leadership and vision of Prof. Ariel Porat, President of TAU, we have become proactive in the entrepreneurship and innovation arenas. We no longer wait for the ‘magic’ to occur. We incorporate entrepreneurship into the curriculum – in the classic disciplines like Computer Science, Engineering, and Management, but also in the Faculties of Humanities, Social Sciences, Law, and the Arts. In fact, most students at TAU can now include an entrepreneurship cluster as an integral part of their studies for a degree, thereby acquiring tools for establishing their own startups, which in the future may become unicorns.”

 

Prof. Moshe Zviran

Prof. Strebulaev’s new index joins a long series of entrepreneurship rankings, all of which rank TAU as the leader in producing entrepreneurs outside the USA. Thus, for example, in 2022, Pitchbook ranked TAU 7th in the world and 1st outside the USA in the number of venture-capital-backed startups founded by alumni. Startup Genome also ranked TAU among the leading universities, right after Stanford, MIT, Harvard, and Berkley, and 1st outside the USA.

“There are many entrepreneurship rankings, each based on different parameters,” explains Prof. Zviran. “All, however, indicate that TAU is the best entrepreneurship incubator in the world outside the USA. We made a strategic decision to position TAU as Israel’s main entrepreneurial university, and proactively buttress our technological and business advantage as a means for producing startups and unicorns. If so far these achievements have been based solely on the outstanding quality of our faculty, students, and curriculum, the focused activities of our Entrepreneurship & Innovation Ecosystem are expected to bring even greater accomplishments.”

Head of Science at the Chan Zuckerberg Initiative Meets TAU’s Scientific Community

Prof. Stephen Quake visited Tel Aviv University and talked about science and collaboration.

Prof. Stephen Quake, the head of science at the Chan Zuckerberg Initiative, visited Tel Aviv University recently and met with its leading scientists.

CZI, which was founded by Facebook’s co-founder Mark Zuckerberg and his wife Priscilla Chan in 2015, is looking to diversify and expand its scientific grant programs, and Quake’s visit was an important step in building cooperation between the Intitative’s and the University’s science communities.

 

“Mark and Priscilla’s goal is to cure, manage or treat all human disease over the course of the century.” 

 

“Mark and Priscilla have decided to give their entire fortune away in their lifetime. Their goal is to achieve a lot … and in science it is to cure, manage or treat all human disease over the course of the century—to try to stimulate the global research community to do it,” said Quake upon being interviewed on Tel Aviv University’s podcast channel, TAU Unbound.

To achieve that, Quake said, CZI’s decision has been “to focus on basic science for a couple of decades—that’s where we think transformative breakthroughs will come from.”

 

 

Currently, CZI is funding research through grants in about 30 different countries, including 9 in Israel. Grant support is given in five broad areas: cell biology, neuroscience, imaging, rare diseases and genome science, and open science, explained Quake.

Another way CZI is catalyzing breakthroughs is by establishing bio-hubs—institutes that partner with “great universities” to take on “a big decade-long problem that they wouldn’t do on their own, be a nexus for driving that collaboration.” For now, CZI has two institutes based in the US, but may consider opening an international bio-hub in the future. “Nobody has all the answers themselves, science goes faster when you share knowledge,” said Quake replying to a question about why international collaboration is important. In the podcast, he also outlined the procedure and criteria for CZI’s grant-giving.

Besides speaking on the podcast, Prof. Quake and the CZI delegation met with a group of TAU’s leading scientists headed by Prof. Dan Peer, TAU’s VP of Research& Development, as well as with the University’s President Prof. Ariel Porat, and the VP for Resource Development, Amos Elad.

“TAU is looking forward to expanding collaboration with the Chan Zuckerberg Initiative, which is an amazing organization with the potential to do great things for humanity,” said President Ariel Porat. 

Destroying Cancer: new drug delivery system containing RNA therapy can target cancer cells in bone marrow

Researchers from Tel Aviv University develop nanoparticles containg RNA molecules,  similar to those used in the COVID-19 vaccine, that inhibit the ability of cancer cells to divide.

Researchers at Tel Aviv University destroyed 90% of the multiple myeloma blood cancer cells under laboratory conditions, and 60% in human tissues taken from patients at Rabin Medical Center (Belinson Hospital), using an RNA-based drug delivered to the cells by targeted lipid nanoparticles.

The researchers developed lipid-based nanoparticles (similar to those used in the COVID-19 vaccine) containing RNA molecules that silence the gene CKAP5, encoding cytoskeleton-associated protein 5. With this protein inhibited the cancer cell is unable to divide, which essentially kills it. To avoid damaging noncancerous cells, the nanoparticles were coated with antibodies that guided them specifically to the cancer cells inside the bone marrow.

The breakthrough was achieved by a group of researchers from Tel Aviv University and the Rabin Medical Center, led by Prof. Dan Peer, a pioneer in the development of RNA therapeutics and Head of the Nanomedicine Laboratory at the Shmunis School of Biomedicine and Cancer Research, also serving as TAU’s VP R&D, and by PhD student Dana Tarab-Ravski. The results were published in the leading journal Advanced Science.

 

Cover image for Advanced Science (credit: Ella Maru Studio)

 

“The targeted drug delivery system we developed is the first to effectively reach cancer cells inside the bone marrow.”

 

Dana Tarab-Ravski explains: “Multiple myeloma is a blood cancer usually found in the older population. While most blood cancers appear in the blood stream or lymph nodes and spread from there to the rest of the body, multiple myeloma cells appear and form tumors inside the bone marrow – and are therefore very hard to reach.”

The study’s findings are very encouraging: under laboratory conditions, where cells are grown in flasks, the nanoparticles developed by the researchers eradicated about 90% of the cancer cells. At the second stage, the new treatment was tested on cancer samples taken from multiple myeloma patients at the haemato-oncological ward of the Rabin Medical Center. The success rate in these samples was 60%. Testing the ability of the nanoparticles to reach the bone marrow in an animal model, the researchers found that after a single injection the RNA had penetrated to 60% of the multiple myeloma cancer cells in the bone marrow. Lastly, examining the therapeutic effectiveness of the nanoparticles in the animal model resulted in eradication of two thirds of the cancer cells, and the animals showed significant improvement in all clinical indicators.

“People with multiple myeloma suffer from severe pain in their bones, as well as anemia, kidney failure, and a weakened immune system,” says Tarab-Ravski. “There are many possible treatments for this disease, but after a certain period of improvement most patients develop resistance to the therapy and the disease relapses even more aggressively. Therefore, there is a constant need for developing new treatments for multiple myeloma. RNA-based therapy has a great advantage in this case because it can be developed very quickly. By simply changing the RNA molecule a different gene can be silenced each time, thereby tailoring the treatment to the progression of the disease and to the individual patient. The challenge in these treatments is to reach the right cells. Today RNA therapeutics are approved for treating a genetic liver disease and for vaccines injected into the muscle, as we saw with the COVID-19 vaccines. The drug delivery system we developed is the first that specifically targets cancer cells inside the bone marrow, and the first to show that silencing the expression of CKAP5 gene can be used to kill blood cancer cells.”

Prof. Dan Peer: “Our technology opens a new world for selective delivery of RNA medications and vaccines for cancer tumors and diseases originating in the bone marrow.”

The clinical team included Dr. Tamar Berger, Dr. Iuliana Vaxman and Prof. Pia Raanani from the Institute of Hematology, Rabin Medical Center, Beilinson Hospital. The research was funded by the the Boaz and Varda Dotan Hematologyoncology Center at Tel-Aviv University and by Lewis Trust for Blood Cancer Research awarded to D.P.

Stress Makes Vaccines Less Effective

Researchers at Tel Aviv University find correlation between behavioral stress and vaccine effectiveness.

Researchers at Tel Aviv University demonstrated for the first time that there is a significant link between behavioral stress and the effectiveness of vaccines. They found that acute stress in lab models 9-12 days after vaccination increases antibody response to the vaccine by 70% compared to the unstressed control group. This, however, comes at the price of reduced antibody breadth, which results in diminished protection against the pathogen’s variants.

 

“Our study was the first to investigate the possible effects of acute stress. We found that this mental state has a dramatic impact – not only on the vaccine’s effectiveness, but also on how it works.” – Dr. Natalia Freund

 

The “Dramatic Impact” of Stress

The study was carried out in Tel Aviv University and led by Ph.D. student Noam Ben-Shalom from the lab of Dr. Natalia Freund at the Faculty of Medicine and Ph.D. student Elad Sandbank from the Neuro-immunology Lab of Prof. Shamgar Ben-Eliyahu at The School of Psychological Sciences and the Sagol School of Neuroscience. The paper was published on July 6th in the leading scientific journal Brain, Behavior, and Immunity.

Dr. Freund explains: “In this study we examined, for the first time, the correlation between stress and the body’s ability to develop an immune response following vaccination. The prevailing assumption is that the effectiveness of a vaccine is determined mainly by its own quality. However, over the years, professional literature has reported influences of other factors as well, such as the age, genetics, and microbiome of the outcomes of vaccination. Our study was the first to investigate the possible effects of acute stress. We found that this mental state has a dramatic impact – not only on the vaccine’s effectiveness, but also on how it works.” 

Classical ‘Fight or Flight’ Response

Acute stress is a mental state caused by immediate threat (either real or imagined), involving the secretion of adrenaline and stimulation. In this study, Dr. Freund and her colleagues vaccinated mice with two different vaccines: the model protein Ovalbumin and a fragment of the SARS-CoV-2 spike protein also used in the COVID-19 vaccine. Nine days later, just as the adaptive immunity became active and the production of antibodies began, the mice were subjected to a widely used behavioral paradigm simulating acute stress. Two and a half weeks after exposure to stress, namely 30 days after vaccination, the level of antibodies in the blood of vaccinated animals that had experienced stress was 70% higher compared to the control group. This phenomenon was observed in animals vaccinated with either type of vaccine.

At the same time, the researchers discovered that the immune system of the animals that had experienced stress was not cross reactive to variants of the protein used in the vaccine. In other words, following stress the immune system was focused entirely on the original vaccine, showing no response to proteins that were only slightly different – such as variants of concern (VOC) of SARS-CoV-2.

 

Dr. Natalia Freund

 

“In general, the purpose of vaccination is not only protection against a specific pathogen, but also creating a long-lasting immunological memory for protection against future mutations of that pathogen.” – Dr. Natalia Freund

 

 

“Initially, we were surprised to find out that the response to the vaccine was much more effective in animals that had experienced stress,” says Dr. Freund, “we would have assumed just the opposite – that stressful situations would have a negative impact on the immune system. Nevertheless, with both types of vaccines, we observed a stronger immune response after stress, both in the blood and in B cells (the lymphocytes that produce antibodies) derived from the spleen and lymph nodes of the immunized mice. The enhancement of the antibodies’ activity following stress was mediated by the cellular receptor that identifies adrenaline – the beta2 adrenergic receptor. When we blocked this receptor, either pharmacologically or by means of genetic engineering, the effects of stress were completely eliminated. On the other hand, to our great surprise, the breadth of the immune response generated by the vaccine was reduced by about 50% following stress. In general, the purpose of vaccination is not only protection against a specific pathogen, but also creating a long-lasting immunological memory for protection against future mutations of that pathogen. In this sense, the vaccines appeared to lose much of their effectiveness after exposure to stress.”

According to the researchers, this is in fact a classical ‘fight or flight’ response, however this time demonstrated at the molecular level. During stress, the immune system produces large quantities of antibodies and stronger antibodies, to address the immediate infection, and this large energetic investment in the here and now comes at the expense of future immunological memory.

Does It Apply to Humans?

Dr. Freund adds: “In the second part of the study we wanted to test whether humans also display the post-stress immune impairment observed in vaccinated mice. For this purpose, we cultured B cells obtained from blood of people who had contracted COVID-19 in the first wave. We then induced stress in these cultures using an adrenaline-like substance that stimulates the beta2 adrenergic receptor, that was identified by us in the first part of the study as a mediator of the response to stress in cells that produce antibodies in mice. B cells express a very high level of these receptors, but until now the receptors’ role in producing antibodies was not known. In fact, it was unclear why these cells need the ability to respond to adrenaline.”

“We discovered that just like in mice, human cells also exhibit a zero-sum game between the intensity and breadth of the immune response. When the adrenaline receptor is activated during stress, the entire immune system is stimulated, generating antibodies that are 100-fold stronger than antibodies produced in cells that had not undergone stress. But here too, the response was narrower: the diversity of antibodies was reduced by 20-100%, depending on the individual from whom the cells were taken.

 

“Stress 9 to 12 days after vaccination, at the time when B cells are generating high affinity antibodies, enhances short-term immunity and damages long-term memory.” – Dr. Natalia Freund

 

RNA sequencing of the cells in which the beta 2 adrenergic receptor was activated, compared to regular cells, indicated that the receptor’s activation caused antibody-producing cells to work at maximum capacity (by activating the PI3 kinase protein and phosphorylation of AKT) – at the expense of antibody breadth and diversity.”

“From the evolutionary perspective,” concludes Dr. Freund, “stress can be caused by different factors. We tend to think of mental stress, but physical illness also causes a form of stress. When the body contracts a virus or bacteria it experiences stress, and signals to the immune system that the top priority is getting rid of the pathogen, while investing energy in long-term immunological memory is a second priority. Therefore, stress 9 to 12 days after vaccination, at the time when B cells are generating high affinity antibodies, enhances short-term immunity and damages long-term memory.”

Victoria

Tok Corporate Centre, Level 1,
459 Toorak Road, Toorak VIC 3142
Phone: +61 3 9296 2065
Email: [email protected]

New South Wales

Level 22, Westfield Tower 2, 101 Grafton Street, Bondi Junction NSW 2022
Phone: +61 418 465 556
Email: [email protected]

Western Australia

P O Box 36, Claremont,
WA  6010
Phone: :+61 411 223 550
Email: [email protected]