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Tag: Escolano

How Does our Immune System Respond to Vaccines? 

A Q&A with Wistar’s Dr. Amelia Escolano

What got you interested in immunology?

My interest in immunology started in college. I took several immunology courses, and I was particularly attracted by antibody biology. One of these courses was Immunotechnology, and I remember being fascinated by the immense potential of antibodies for immunotherapy development. This interest further developed during my Ph.D. studies, which focused on macrophages, a type of immune cell. I investigated the role of calcineurin, a phosphatase enzyme, in macrophage polarization. In other words, I studied how calcineurin determined the specific pro- or anti-immune functions of macrophages and how this could impact the progression and outcomes of inflammatory processes.

The immune system is immensely complex. It is a very sophisticated and orchestrated network of immune mediators that interact and influence each other to provide protection against pathogenic threats. We have so much to learn about the many different immune cells and the cellular and molecular mechanisms involved in immune responses; the complexity and ingenious mechanisms of the immune system make it a very exciting area of study.

In addition to my interest in shedding light on some aspects of the immune response, the fact that the implications of immune system research are so clearly beneficial to human health makes this area of research very attractive to me and my team.

Now, in your lab, you investigate the mechanisms governing the immune responses to vaccines. Very broadly, can you tell us about that work?

Our research revolves around vaccine design; that’s the goal that informs our approach. We are interested in understanding how B cells and T cells respond to vaccination so that we can leverage this information to design better vaccines. In particular, we study the process of antibody affinity maturation.

Affinity maturation is the process by which antibodies are produced and refined to target a specific antigen, a component of a pathogen that activates the immune system. Antibody affinity maturation takes place in the germinal centers, which are anatomical sites where B cells work with a certain kind of T cell called T follicular helper (Tfh) cells to iteratively refine and test their B cell receptors — otherwise known as antibodies. This process allows the immune system to improve its antibody responses.

With this process in mind, we aim to understand how a vaccine should be designed so that the elicited antibody response can efficiently prevent infectious diseases for long periods of time.
In my lab, we study the immune response to sequential immunization in the context of HIV-1. Sequential immunization is a novel form of vaccination that requires multiple boost immunizations with different but related viral proteins. In the case of HIV-1, sequential immunization involves multiple boost immunizations with different versions of the envelope protein of HIV-1.

Sequential immunization takes advantage of the antibody affinity maturation process with the ultimate goal of getting the immune system to produce high-quality antibodies that can fight complex, highly variable viruses like HIV.

We analyze how B cell populations and their antibodies evolve in response to sequential immunization, and we’re testing strategies to make that antibody affinity maturation more efficient by focusing on both B cells and T follicular helper cells.

Why is sequential immunization necessary against HIV-1?

To vaccinate effectively against HIV, we need B cells to produce what we call a broadly neutralizing antibody, or bNAb. bNAbs are rare antibodies that can neutralize multiple different variants of HIV-1, and we expect a vaccine that elicits bNabs to protect effectively against HIV-1.

Our previous work showed that repeated immunization with the same HIV-1 envelope protein was not capable of inducing bNAbs. Instead, sequential immunization efficiently induced antibodies that potently neutralized a large number of different HIV-1 variants.

In a sequential immunization protocol, we start with an engineered HIV-1 envelope immunogen, which is a term that we use to describe an antigen we’re testing as a vaccine candidate. The role of this first immunogen is to activate a rare subset of B cells that have receptors with the capacity to be refined into bNAbs. These B cells respond to this first immunogen and increase their affinity for it.

That increase in affinity for the first immunogen is associated with an increase in affinity for a slightly more complex HIV-1 envelope immunogen, which is then used for a second immunization. Sequential immunization repeats this process multiple times as a way of gradually increasing the affinity of B cells for the unmodified wild-type, or naturally occurring, HIV-1 envelope protein. We nudge B cells along to make sure that they mature in a way where they get progressively better at reacting to different HIV-1 strains.

How are you able to tell that your sequential vaccination protocol has produced a broadly neutralizing antibody? What do you look for?

We test our sequential immunization protocols by looking at blood after vaccination and running what’s called a serum neutralization assay. This assay can determine whether the mix of antibodies in the blood, elicited upon vaccination, can neutralize different HIV-1 strains. The number of different HIV-1 strains that the serum antibodies can neutralize determines the breadth of these antibodies. This assay also informs us of the potency of the antibodies to neutralize each HIV-1 strain.

In addition to these neutralization assays, we analyze B cells from lymph node tissue to see which antibodies they’re expressing. We are then able to evaluate individual antibodies for their capacity to neutralize HIV-1. These evaluations help us refine our vaccine candidates and sequential immunization protocols by showing us what’s working and what isn’t.

For how long has this immunology work been your focus?

I’ve been working on this approach for HIV vaccine development since I started my postdoctoral studies in the Nussenzweig laboratory at The Rockefeller University in 2014. Now, at The Wistar Institute, where I established my independent lab two years ago in September of 2021, my lab is expanding this research.

I came to The Wistar Institute with a vision of what I wanted my science to be, and Wistar has helped make that vision a reality. Here, I have found great colleagues, I have established fantastic collaborations both at Wistar and UPenn and I have seen my program grow exponentially. I’ve also found great opportunities to explore other research areas that have strengthened my program’s approach.

I find it hard to believe that two years have gone by already; the time has been both positive and productive. The welcome and support I’ve had at Wistar make me feel like a real part of a community. I can tell that all my Wistar colleagues — across the labs, across the departments — have an investment in seeing our science succeed.

Wistar’s Dr. Amelia Escolano Earns NIH Director’s New Innovator Award

PHILADELPHIA — (OCTOBER 4, 2022) — The National Institutes of Health has awarded Amelia Escolano, Ph.D., assistant professor in The Wistar Institute’s Vaccine & Immunotherapy Center, the 2022 NIH Director’s New Innovator Award. The honor provides Escolano with a $1.5 million grant given in two parts over a total of five years. The prestigious New Innovator Award recognizes exceptionally innovative, early career scientists proposing high-impact research with unconventional approaches to major biomedical and behavioral research challenges.

Escolano completed her scientific training in Spain, Finland, and the United States. She was recruited to Wistar in 2021 and has since focused her research on identifying guidelines for the design of vaccines that will induce long term protection against viruses that mutate frequently in humans such as HIV, influenza, and potentially future variants of SARS-CoV2. With the award, Escolano intends to expand her work on designing universal vaccines by assessing novel sequential immunization strategies, developing broadly effective antibodies, and tracking immune cell interactions upon repeated vaccination.

“It is an honor to be recognized for the NIH Director’s New Innovator Award. I am grateful to the NIH and excited that this opportunity will accelerate my work in innovative vaccine design to address some of the world’s most pressing health challenges,” Escolano shares.

As a recipient of the 2022 NIH New Innovator Award, Escolano was also invited to attend the High-Risk, High-Reward Research Symposium in summer of 2023. The NIH makes approximately 100 NIH Director’s awards each year depending on the availability of funds, including the NIH Director’s Pioneer Award, the NIH Director’s Transformative Research Award, the NIH Director’s Early Independence Award and NIH Director’s New Innovator Award. These awards are funded and administered by the Office of the Director and 27 Institutes and Centers across the National Institutes of Health. Escolano was also named a 2022 Pew Scholar this summer in support of her breakthrough research.

Dario C. Altieri, M.D., Wistar president & CEO, director of the Ellen and Ronald Caplan Cancer Center, and the Robert and Penny Fox Distinguished Professor said, “Wistar science is a leading force in developing biomedical solutions of the future, and Amelia’s work is testament to some of our most transformative research projects toward vaccines and immunotherapies. We are extremely proud of her for this prestigious recognition.”

Grant Information: DP2AI175470

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The Wistar Institute marshals the talents of an international team of outstanding scientists through a highly enabled culture of biomedical collaboration and innovation, to solve some of the world’s most challenging and important problems in the field of cancer, immunology, and infectious diseases, and produce groundbreaking advances in world health. Consistent with a pioneering legacy of leadership in not-for-profit biomedical research and a track record of life-saving contributions in immunology and cell biology, Wistar scientists pursue novel and courageous research paths to life science discovery, and to accelerate the impact of early-stage discoveries by shortening the path from bench to bedside. wistar.org

Wistar’s Dr. Amelia Escolano Named 2022 Pew Scholar

PHILADELPHIA — (JUNE 14, 2022) — The National Advisory Committee of the Pew Scholars Program in the Biomedical Sciences, has chosen Amelia Escolano, Ph.D., Assistant Professor in The Wistar Institute’s Vaccine & Immunotherapy Center, to join their 2022 cohort of Scholars. The honor provides Escolano with a grant of $300,000 over four years, starting in August 2022. A signature piece of the award provides support for Escolano to attend the annual five-day meeting with fellow Scholars to bolster a collaborative research community over the duration of the award.

Escolano completed her education and scientific training across several countries – Spain, Finland, and the United States. Recruited to Wistar in 2021, she has since made great strides in her work on new vaccination approaches for highly mutating viruses like HIV-1. The Pew Scholar funding will support her project to develop innovative approaches to investigate the immune response to vaccination that will be the basis to eventually design universal vaccines against mutating viruses – a pressing global health challenge.

“I want to thank The Pew Charitable Trusts (Pew) for this tremendous honor and for their support of my research. I look forward to participating in the annual meeting and engaging with the incredible community of Scholars, current and past.” expresses Escolano.

Pew Scholars are chosen from a pool of highly talented, early career investigators nominated by leading scientific universities and institutions around the United States. Pew supports these Scholars with research funding as they tackle unanswered biomedical questions and improve scientific innovation. The award also opens the door to a collaborative network of scientists and mentorship from leading scientific minds from the program’s national advisory committee.

“We are extremely proud of Amelia and this outstanding recognition in one of the most prestigious and competitive venues ever—she is one of 22 Scholars across the nation selected for this prestigious award,” said Dario C. Altieri, M.D., Wistar president & CEO, director of the Ellen and Ronald Caplan Cancer Center, and the Robert and Penny Fox Distinguished Professor. “The combination of bold ideas, innovative science, and commitment to improve human health is at the core of both The Wistar Institute and the Pew Scholars program: Amelia is an exceptional candidate who embodies those values as she tackles some of the most impactful, transformative research questions in immunology and infectious diseases.

The views expressed are those of the author(s) and do not necessarily reflect the views of The Pew Charitable Trusts.

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The Wistar Institute is an international leader in biomedical research with special expertise in cancer research and vaccine development. Founded in 1892 as the first independent nonprofit biomedical research institute in the United States, Wistar has held the prestigious Cancer Center designation from the National Cancer Institute since 1972. The Institute works actively to ensure that research advances move from the laboratory to the clinic as quickly as possible. wistar.org.

Highlighting Vaccine Research at The Wistar Institute Through the Penn-CHOP-Wistar Vaccine Symposium

From HIV to COVID-19, Wistar scientists are at the forefront of vaccine development. Read our recap of the recent Vaccine Symposium and the impactful research in progress at the Institute.

This past Monday, The Wistar Institute, University of Pennsylvania Perelman School of Medicine, and Children’s Hospital of Philadelphia held the Penn-CHOP-Wistar Vaccine Symposium. Hosted both in-person at the Smilow Center for Translational Research and online, the all-day event covered the history of vaccines and current vaccine research from the three sponsoring institutions.

Keynote speaker and Wistar professor emeritus Stanley Plotkin, M.D., is a prominent researcher who is known for the development of the rubella vaccine while he was a virologist at The Wistar Institute. Furthermore, his years of work helping in vaccine efforts for rabies, rotavirus, and cytomegalovirus have stimulated much innovation in the biomedical research community.
After giving a brief history of vaccines, Plotkin proclaimed “Vaccinology has taken off. … We are now in a golden age of vaccinology.”

The Symposium’s research presentations opened with Wistar’s Daniel Kulp, Ph.D., Associate Professor in the Vaccine & Immunotherapy Center, and his work on a novel COVID-19 nanoparticle vaccine. Amelia Escolano, Ph.D., Assistant Professor in the Vaccine & Immunotherapy Center, also spoke about her efforts investigating immunization strategies for HIV. Wistar’s Vaccine & Immunotherapy Center Director David B. Weiner, Ph.D., gave a summary of his research into the genetic delivery of vaccines, calling the innovation of vaccinology in Pennsylvania among these institutions “extraordinary”.

The current global pandemic has reinforced the need for scientific solutions and a deeper understanding of human diseases. It is the studies and ideas from research centers like The Wistar Institute and its colleagues that propel forward biomedicine. As keynote speaker Plotkin stated, “Pandemics have occurred throughout the history of humankind and will continue to do so in the future. Infectious diseases of humans will continue to happen. Therefore, we must act against them.”

Destined for Science, Amelia Escolano, Ph.D., Develops New Vaccination Strategies to Outsmart HIV-1, and Other Highly Mutating Pathogens

Scientists developed COVID-19 vaccines in record time — less than a year after the genome of the virus was sequenced, countries started authorizing use of multiple vaccines. But the virus is rapidly changing, and new variants have been emerging that are more likely to overcome the protective barrier from vaccination.

Amelia Escolano, Ph.D., who became an assistant professor at The Wistar Institute in September, wants to help science regain the advantage. During her postdoctoral studies at The Rockefeller University, she pioneered a new form of vaccination against HIV. She proved that this type of vaccination regimen involving sequential immunization would be necessary to induce broad protection against HIV. At The Wistar Institute, one of her first research goals will be wielding what she learned in her postdoctoral work to develop universal vaccines against HIV-1, other viruses — including cancer-associated-viruses, and tumor neoantigens.

Branching Out

For Amelia, everything clicked about being at Wistar. “It is exactly the kind of place I was looking for,” she said. She thinks the size of the institute is just right for sparking discussion and collaboration. Amelia is already feeling the support of her new colleagues, and excited about all the disciplines she will be exposed to through interactions with scientists at neighboring academic institutions, such as the University of Pennsylvania.

Although her postdoctoral project at The Rockefeller University centered largely around HIV, Amelia looks forward to casting a wide net in her own lab. “The fact that the Cancer Center is here is going to open up new avenues of research and synergies,” Amelia said. She is already brainstorming with several new colleagues at Wistar about how they could collaborate to design vaccination strategies against cancer–associated viruses and tumor neo-antigens.

A Scientist is Born

Amelia cannot think of a time when she did not want to be a scientist. Both of Amelia’s parents were chemists so it would seem to be in her blood.

Amelia’s first hands-on experience happened when she was only about four years old and she received a little microscope as a gift. She dashed outside to collect bugs and puddle water from the backyard of her home in a small village in northern Spain and then sprawled out on the floor to study the specimens using her new equipment. Amelia’s decision to focus on biology was also a no-brainer as soon as she started learning about the cell in school. “I was actually fascinated by the cell and the size of molecules, and how such tiny things could have such interesting functions,” Amelia said.

Amelia had some setbacks in her career and sometimes muses about why she has stuck it out in science. “I must really love it” is the only answer she can provide. “The satisfaction you feel when things finally work makes you forget all the failure the months before,” Amelia said. It is the thrill of knowing that “you had this important question and then your experiment gave an answer and nobody else at the moment knows it,” she explained.

Next Steps

At the heart of the strategy to make a universal HIV-1 vaccine is injecting a series of different versions of a viral component, in this case part of the HIV-1 envelope protein. This strategy is believed to be necessary to induce a broadly protective immune response against HIV-1. Amelia showed during her postdoctoral studies that the first of these injections had to be with a highly engineered envelope protein and that using more natural versions of this component for subsequent injections helped achieve the desired result: broadly neutralizing antibodies that can protect against many different strains of HIV-1. She will continue animal studies at Wistar to optimize sequential immunization approaches.

When Amelia started hearing about COVID-19, she immediately thought that SARS-CoV-2 which causes COVID-19, could be a target for sequential immunization. She suspects this virus will be an easier target than HIV-1 because of the lower mutation rates. She thinks a series of injections with natural versions of spike from a range of newly emerging SARS-CoV-2 strains may lead to broad protection from multiple variants. Amelia sees no limit to the applications of this approach to viruses and bacteria. “The same approach can be translated for all types of pathogens in general that mutate over time,” she said.

Building a Platform

Amelia expected some challenges at the time of recruiting personnel as an early-stage investigator, however, she has been pleasantly surprised. “People are interested in the projects,” Amelia said. “My previous work on vaccine design was well-timed so that I can now join the current research workforce aiming to develop new vaccines”.

As a Finalist in the prestigious Blavatnik Regional Awards for Young Scientists in 2020, Amelia has been more motivated than ever to use her special platform to push for the advancement of women in science and all STEM fields. In addition to trying to support and inspire the many female scientists she has mentored, Amelia speaks out to increase representation of women in different scientific environments. She hopes to continue these efforts taking advantage of her new position at The Wistar Institute.

As she grows her research program, Amelia has no shortage of hobbies to help take her mind off science’s many roadblocks. She loves running and just about all outdoor activities. She also disconnects from work by drawing cartoons of characters that live in her imagination. Amelia has even entertained the idea of illustrating books to promote science to help give the next generation of scientists the excitement she had as a young kid.

Written by, Carina Storrs, Ph.D.

The Wistar Institute Recruits Vaccine Researcher Amelia Escolano, Ph.D., and Immunologist Nan Zhang, Ph.D., as Assistant Professors

PHILADELPHIA — (Sept. 1, 2021) — The Wistar Institute, an international biomedical research leader in cancer, immunology and infectious diseases, welcomes Amelia Escolano, Ph.D., and Nan Zhang, Ph.D., as assistant professors.

Escolano’s research focuses on the development of novel vaccine approaches against highly mutating viruses. She will join the Vaccine & Immunotherapy Center.

“My laboratory will investigate the immune responses elicited by a new form of vaccination that involves sequential immunization. Our goal will be to identify guidelines for the design of efficacious vaccines that induce broad protection for prolonged periods of time,” said Escolano. “I also plan to establish collaborations with members of Wistar’s Cancer Center in order to explore the use of our sequential vaccination approaches against cancer-related viruses and tumor neoantigens.”

Zhang, who joins the Immunology, Microenvironment and Metastasis Program of The Wistar Institute Cancer Center, studies the role of a group of white blood cells known as macrophages during ovarian cancer metastasis in the abdominal cavity.

“Because of recent developments in macrophage research, these cells are known to be highly plastic and heterogenous, meaning that depending on their surrounding environment they can either promote or suppress tumor growth and form different subgroups that are very difficult to identify and to target pharmaceutically,” said Zhang. “My lab will use cutting-edge technologies to better understand the functional differences among these macrophage subgroups and eventually find a treatment plan for this devastating disease.”

“We are delighted to be able to recruit top talent to our scientific community,” said Dario Altieri, M.D., Wistar president and CEO, director of The Wistar Institute Cancer Center and the Robert and Penny Fox Distinguished Professor. “Nan and Amelia have outstanding research records in finding answers to some of the most pressing and timely questions in cancer and HIV, and have done so using cutting-edge models and technologies. We can’t wait to witness their potential unfold and to see what new research frontiers they will conquer.”

“I’m excited to join an institution with such an important history of contributions to the vaccine design field and where my research can synergize with that of other outstanding members of the Vaccine & Immunotherapy Center,” said Escolano. “I am thrilled to have the opportunity to develop my own scientific ideas and create a community of researchers around them. It is my goal to transmit my passion for science to the new generations and train a solid group of researchers who will significantly influence scientific progress.”

“I have always admired the collaborative, world-class research environment at Wistar, particularly in cancer biology and immunology, and thought the Institute would be a perfect fit for me given my mutual research interests with other investigators,” Zhang said. “I feel like I’m about to embark on some of the most thrilling adventures one could ever have — making new discoveries that can potentially save people’s lives and mentoring next-generation scientists.”

Escolano earned her B.S. from the University of Oviedo, Spain, and University of Turku, Finland, and a master’s degree from Centro de Biología Molecular Severo Ochoa, Madrid, and Genome Research Institute (GRI), Cincinnati, Ohio. She obtained her Ph.D. in biochemistry and molecular biology from the Spanish Center for Cardiovascular Research, Madrid, and Autonoma University, Madrid, and completed her postdoctoral training at The Rockefeller University, New York.

Zhang received his B.S. in microbiology and immunology from Shandong University, China, and a Ph.D. in biochemistry and molecular biology from the University of Oklahoma Health Sciences Center. He completed his postdoctoral training in the Department of Pathology and Immunology of Washington University School of Medicine.

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The Wistar Institute is an international leader in biomedical research with special expertise in cancer research and vaccine development. Founded in 1892 as the first independent nonprofit biomedical research institute in the United States, Wistar has held the prestigious Cancer Center designation from the National Cancer Institute since 1972. The Institute works actively to ensure that research advances move from the laboratory to the clinic as quickly as possible. wistar.org.

Wistar Welcomes Assistant Professors Amelia Escolano, Ph.D., and Nan Zhang, Ph.D.

Wistar is pleased to welcome two new assistant professors starting September 1.

Dr. Amelia Escolano researches new vaccine approaches against highly mutating viruses. She will join the Vaccine & Immunotherapy Center.

“I am thrilled to have the opportunity to develop my own scientific ideas and create a community of researchers around them,” said Dr. Escolano. “I look forward to establishing new collaborations and exploring new branches of my research at Wistar, and am excited to have a platform from which I will be able to support women in science.”

Dr. Nan Zhang studies the role of immune cells called macrophages in ovarian cancer metastasis to find new therapies for this disease. He will join the Immunology, Microenvironment and Metastasis Program of the Cancer Center.

“Learning how to be proficient at securing funding for my lab, hiring and managing staff are big responsibilities,” Dr. Zhang said. “But these challenges bring some of the most thrilling adventures one could ever have — making new discoveries that can potentially save people’s lives and mentoring next-generation scientists.”

The Institute’s faculty continues to expand to include new relevant expertise and strengthen our scientific efforts on the forefront of cancer, immunology and infectious disease research.