Optimized ACE2 decoys neutralize antibody-resistant SARS-CoV-2 variants through functional receptor mimicry and treat infection in vivo

As a result of evolution under the selective pressure of early-stage pandemic therapeutics and vaccines, plus natural immunity, ​​severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is becoming endemic. Concerns rise as SARS-CoV-2 variants continue to emerge with resistance to currently available monoclonal antibody therapeutics. Recent research led at Dana-Farber Cancer Institute and with direct involvement of the VIC team at Mass General Hospital, investigates the potential in developing a decoy drug therapy that may be capable of treating common and arising variants of SARS-COV-2. The decoy drug uses angiotensin-converting enzyme 2 (ACE2) decoy receptors, previously proposed as a therapeutic for COVID-19. These ACE2 decoy receptors engage the receptor binding domain of the viral S protein and outcompete human cell-surface viral binding, effectively neutralizing viral infection. Also, as the viral binding domain of the ACE2 decoy is identical to cell-surface ACE2, resistant variants are not likely to emerge as any mutations that reduce affinity of the virus for the decoy reduces viral infectivity. Research findings provide new insight to ACE2 decoy functionality and indicate potential in further development as a therapeutic for ACE2-dependent coronaviruses.
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Keystone Symposium selects Dr. Alagpulinsa for 2023 Fellows Program

David Alagpulinsa, PhD, Instructor in Medicine and Investigation at the MGH Vaccine and Immunotherapy Center (VIC) and Harvard Medical School, has been selected to participate in the 2023 Keystone Symposia Fellows Program. Commenting on his selection to the program, Dr. Alagpulinsa noted a previous encounter with Keystone Symposia: “Many years ago whilst studying for a master’s degree in Pharmacology in Ghana, I won a Keystone Symposia Global Health Travel Award to attend a Keystone Symposia conference in Banff, Canada. Attending this conference formed the genesis of my scientific career abroad; I felt left out by most of the science that was presented at the conference because I didn’t have the kind of training and expertise to fully understand. Prior to that, I didn’t have any interest in schooling abroad, but I suddenly developed a strong longing to pursue my doctorate degree abroad, specifically the US because most of the scientists I met were from there. Now, I’m here embarking on biomedical research that I’m passionate about, thanks to Keystone Symposia.”

Dr. Alagpulinsa’s current research at VIC focuses on defining the mechanisms that underlie abnormal bone marrow and hematopoietic stem cell function that may contribute to disease etiology, specifically type 1 diabetes and cardiovascular disease.

Expressing gratitude for his selection to participate in the Keystone Symposia Fellows program, Dr. Alagpulinsa comments that “This program aims to provide the necessary training, network, and skills for early-career scientists from diverse populations to take on leadership and decision-making roles in academia or industry and I’m looking forward to having a great experience.”

The Keystone Symposium has served the biomedical and life sciences community for more than 50 years, acting as a key connector between eminent scientists across academic, industry, and government disciplines to provide a space for cross-disciplinary discussion and collaboration that lead to scientific breakthroughs monumental to humankind. Through the Fellows Program, early-career scientists from underrepresented and disadvantaged backgrounds have access to unparalleled professional advancement opportunities including career-development workshops and related hands-on immersion experience, directly collaborating with distinguished scientists of the Scientific Advisory Board. The program focuses on accelerating the career development of selected scientists, generating a network to improve key skills necessary to pursue and achieve career goals.

Novel HIV vaccine approach shows promise in first-in-human clinical trial

Early findings from a publication between Scripps Research, IAVI, Dred Hutch, VRC, and other collaborators show encouraging results in hopes of boosting immunity against HIV. In the first- in-human test of the germline-testing strategy, the novel HIV vaccine approach showed promise, inducing broadly neutralizing antibodies (bnAbs), a rare antibody, previously indicated to protect against a wide range of HIV variants. Through the stimulation of the bnAb immune cells- precursor B cells, researchers have accomplished the first step to potential immunity against HIV. 

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Dr. Poznansky Gives an Invited Research Talk about Latest Advances at VIC

Dr. Poznansky gives an invited research talk about latest advances at VIC with the development of a novel self-assembling vaccine platform at the Vaccines R and D international summit in Boston this month. This work is partnered with Voltron Therapeutics Inc. The company and its leadership are supporting product development and progress towards first in human studies with a self-assembling vaccine for cervical and head and neck cancer.

Investigating Cancer Immunotherapy Effects on COVID-19 Outcomes

Recent findings from research led by University of Cincinnati researcher Trisha Wise-Drapher illuminate the effect of immunosuppression and immunotherapy for patients with cancer and COVID-19. This investigation began with a primary focus on understanding the effects of immunotherapy on COVID-19 severity, specifically if immunotherapy treatment is associated with worse clinical outcomes for cancer patients with COVID-19. The data of 12,046 patients was reviewed and evaluated with metrics including: whether patients were admitted to the hospital, if they required oxygen, or required ICU care. These analyses suggest that patients infected with SARS-CoV-2 that had baseline immunosuppression and followed immunotherapy treatment may have poorer clinical outcomes, whereas patients with immunotherapy alone had no change in outcome quality.
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A novel cuproptosis-related immune checkpoint gene signature identification and experimental validation in hepatocellular carcinoma

As current staging systems for cancer are typically found through anatomical evaluations of the disease, stratification of patients for treatment and further therapy strategies prove difficult. Much potential remains in cancer biomarker research for the identification of prognostic gene expression signatures capable of classifying tumor subgroups via their biological counterparts. With the advancements in genomic and transcriptomic technologies, researchers are making great discoveries in cancer biomarkers for detection, prediction of therapeutic response and prognoses of cancer. Recent research highlights a new cuproptosis (copper-induced death) related immune checkpoint gene signature recently investigated as a potential biomarker for anticancer therapy for hepatocellular carcinoma. 

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Cancer-seeking molecular delivery system could boost immunotherapy drug, research finds

For past decades, the treatment of cancer has generally meant surgery, radiation, chemotherapy, or a combination of the above. Through recent work from a collaboration of researchers from the University of Rhode Island and Yale University comes the promising new approach of delivering immunotherapy agents, STING agonists, via a cancer-seeking molecular delivery system. The delivery relies on the acid-seeking molecule- pHLIP. These molecules deliver cargo directly to the tumor environment via targeting of the high acidity of cancerous tumors. Through this novel drug delivery technique, cancer immunotherapy may become even more effective.

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VIC lab members enjoying social gatherings this summer.

Lab members gathered on a sunny July afternoon for the annual VIC at Myopia Polo event alongside VIC friends and family. Cocktails and hors d’ oeuvre’s were enjoyed while socializing and watching the competitive tournament play.

Liam Dwyer was presented with the Will Tankard Scholar Award as the most dedicated young scientist at VIC in 2022. This award is given out in memory of a courageous young polo player dedicated to improving his craft.

Lab members took the opportunity to gather for a pot luck picnic with many members contributing delightful homemade treats representative of their home countries.

Undergraduates enjoy a successful summer internship at VIC!

VIC hosted six undergraduate student interns this summer

Alice Barocco and Jacob Smith came from Imperial College, London. The Professor Dulcie Coleman Endowed Student Training Award is sponsored by Dr. Mark Poznansky in memory of his mother who was an eminent research scientist at Imperial College. This is a competitive application process and the top two students were both given the award this year.

James Adeosun came from Clare College, Cambridge University, where Dr. Poznansky studied for his PhD.. A top student is selected internally and interviewed and approved by Dr. Poznansky.

Saumya Maheshwari came from Edinburgh University Medical School. Dr. Poznansky gained his undergraduate and medical degrees at this institution. This is the first year this program has been implemented and there was an overwhelming number of applications.

Katie Lu is an undergraduate at Stamford University and successfully applied for the Vaccine and Immunotherapy Center Summer Research Studentship Program.

Jolade Adebekun is an undergraduate at Harvard University and joined us at VIC though the Summer Research Training Program (SRTP) organized by the Center for Diversity and Inclusion at MGH.

All of the students join us for a period of 12 weeks and are mentored by VIC Principal Investigators and Senior Scientists and have the opportunity to contribute to relevant ongoing research studies and to be included on the resulting publications. This has been a highly motivated group who have integrated into the lab exceptionally well over the summer and it has been a pleasure to spend time with them.