Science-Watching: Proton-Coupled Energy Transfer/Omicron Spike Function

[from Science, First Release Notification for July 21]

Proton-Coupled Energy Transfer in Molecular Triads

Abstract

A photochemical mechanism was experimentally discovered and denoted proton-coupled energy transfer (PCEnT). A series of anthracenephenolpyridine triads formed the local excited anthracene state after light excitation at ca. 400 nm, which led to fluorescence around 550 nm from the phenolpyridine unit. Direct excitation of phenolpyridine would have required light around 330 nm, but the coupled proton transfer within the phenolpyridine unit lowered its excited state energy so that it could accept excitation energy from anthracene. Singlet-singlet energy transfer thus occurred despite the lack of spectral overlap between the anthracene fluorescence and the phenolpyridine absorption. Moreover, theoretical calculations indicated negligible charge transfer between the anthracene and phenolpyridine units. PCEnT was suggested as an elementary reaction of possible relevance to biological systems and future photonic devices.

Access the full paper [via institutional access or paid download].

Omicron Spike Function and Neutralizing Activity Elicited by a Comprehensive Panel of Vaccines

Abstract

The SARS-CoV-2 Omicron variant of concern comprises several sublineages with BA.2 and BA.2.12.1 having replaced the previously dominant BA.1, and BA.4 and BA.5 increasing in prevalence worldwide. We show that the large number of Omicron sublineage spike mutations lead to enhanced ACE2 binding, reduced fusogenicity, and severe dampening of plasma neutralizing activity elicited by infection or seven clinical vaccines relative to the ancestral virus. Administration of a homologous or heterologous booster based on the Wuhan-Hu-1 spike sequence markedly increased neutralizing antibody titers and breadth against BA.1, BA.2, BA.2.12.1, and BA.4/5 across all vaccines evaluated. Our data suggest that although Omicron sublineages evade polyclonal neutralizing antibody responses elicited by primary vaccine series, vaccine boosters may provide sufficient protection against Omicron-induced severe disease.

Read the full paper. [Archived PDF]

“2022 Monkeypox Outbreak: Situational Awareness” with Syra Madad [Zoom]

[from Harvard Kennedy School’s Belfer Center, part of Harvard University]

Thursday, July 21, 2:30-4:00 PM EDT

RSVP (Required)

The 2022 Monkeypox outbreak continues to expand with case counts mounting in many countries. This seminar will cover where we are in the global fight against monkeypox, where we may be headed as a nation, and what we need to do right now to mitigate the growing threat of monkeypox. Join Belfer Fellow Dr. Syra Madad in conversation with Kai Kupferschmidt, Dr. Krutika Kuppalli, Dr. Anne Rimoin, Dr. Boghuma Kabisen Titanji, and Dr. Jay K. Varma.

About the Speakers

Dr. Anne Rimoin is a Professor of Epidemiology at the UCLA Fielding School of Public Health. She is the Gordon-Levin Endowed Chair in Infectious Diseases and Public Health. Dr. Rimoin is the director of the Center for Global and Immigrant Health and is an internationally recognized expert on emerging infections, global health, surveillance systems, and vaccination.

Rimoin has been working in the DRC since 2002, where she founded the UCLA-DRC Health Research and Training Program to train U.S. and Congolese epidemiologists to conduct high-impact infectious disease research in low-resource, logistically-complex settings.

Dr. Rimoin’s research focuses on emerging and vaccine-preventable diseases. It has led to fundamental understandings of the epidemiology of human monkeypox in post-eradication of smallpox, long-term immunity to Ebola virus in survivors and durability of immune response to Ebola virus vaccine in health workers in DRC. Her current research portfolio includes studies of COVID-19, Ebola, Marburg, Monkeypox and vaccine-preventable diseases of childhood.

Boghuma Kabisen Titanji (MD, MSc., DTM&H, PhD) is a Cameroonian born physician-scientist and Assistant Professor of Medicine at Emory University in Atlanta. She obtained her MD from the University of Yaoundé I in Cameroon and worked for two years after graduation as a medical officer, before pursuing post-graduate research training in London, United Kingdom. As an awardee of the prestigious Commonwealth Scholarship program, she obtained a Masters Degree in Tropical Medicine and International Health from the London School of Hygiene and Tropical Medicine, a diploma in Tropical Medicine and Hygiene from the Royal College of Physicians and a Ph.D. in Virology from University College London. Dr. Titanji joined Emory University School of Medicine in 2016 where she completed a residency in Internal Medicine, on the ABIM research pathway and a fellowship Infectious Diseases. She has three parallel career interests: translational and clinical research in HIV and emerging virus infections, science communication, and global health. Her clinical focus is general infectious diseases and people with HIV. Her current research focuses on chronic inflammation as a mediator of cardiovascular disease in people with HIV. She is passionate about leveraging translational research to improve the care of people with HIV, global health equity and using science to influence health policy through science communication and advocacy.

Jay K. Varma, MD is a Professor of Population Health Sciences and Director of the Cornell Center for Pandemic Prevention and Response at Weill Cornell Medicine. Dr. Varma is an expert on the prevention and control of diseases, having led epidemic responses, developed global and national policies, and led large-scale programs that have saved hundreds of thousands of lives in China, Southeast Asia, Africa, and the United States. After graduating magna cum laude with highest honors from Harvard, Dr. Varma completed medical school, internal medicine residency, and chief residency at the University of California, San Diego School of Medicine. From 2001-2021, he worked for the U.S. Centers for Disease Control and Prevention with postings in Atlanta, Thailand, China, Ethiopia, and New York City. From April 2020 – May 2021, he served as the principal scientific spokesperson and lead for New York City’s COVID-19 response. Dr. Varma has authored 143 scientific manuscripts, 13 essays, and one book.

Kai Kupferschmidt is a science journalist based in Berlin, Germany. He is a contributing correspondent for Science where he often covers infectious diseases. Kai received a diploma in molecular biomedicine from the University of Bonn, Germany and later visited the Berlin Journalism School. He has won several awards for his work, including the Journalism Prize of the German AIDS Foundation. Together with two colleagues he runs a podcast on global health called Pandemia [German]. He has also written two books, one about infectious diseases and one about the science of the color blue.

Krutika Kuppalli, MD, FIDSA is a Medical Officer for Emerging Zoonotic Diseases and Clinical Management in the Health Emergencies Program at the World Health Organization where she currently supports activities for the Monkeypox outbreak and COVID-19 pandemic. She completed her Internal Medicine residency and Infectious Diseases fellowship at Emory University, a Post-Doctoral Fellowship in Global Public Health at the University of California, San Diego and the Emerging Leader in Biosecurity Fellowship at the Johns Hopkins Center for Health Security. Dr. Kuppalli currently serves on the American Society of Tropical Medicine and Hygiene (ASTMH) Trainee Committee and is the Chair of the Infectious Diseases Society of America (IDSA) Global Health Committee.

Dr. Kuppalli was previously awarded the NIH Fogarty International Clinical Research Fellowship and conducted research in Southern India to understand barriers to care and how emerging infections impacted persons living with HIV/AIDS. She was the medical director of a large Ebola Treatment Unit in Sierra Leone during the 2014 West Africa Ebola outbreak, helped lead the development and implementation of pandemic response preparedness activities in resource limited settings, and has consulted on the development of therapeutics for emerging pathogens. Her clinical and research interests focus on health systems strengthening in resource limited settings, research and clinical care for emerging infections, outbreak preparedness and response, and policy. She has worked in numerous countries including Ethiopia, India, Sierra Leone, Uganda, and Haiti.

During the COVID-19 pandemic Dr. Kuppalli served as a consultant for the San Francisco Department of Health and helped develop and operationalize a field hospital. She served as an expert witness to the U.S. Congress, Financial Services Committee Task Force on Artificial Intelligence (AI) about how digital technologies may be leveraged for exposure notification and contact tracing to improve the pandemic response. She also collaborated with the Brennan Center for Justice to develop guidelines to inform “Healthy in-person Voting” in advance of the 2020 U.S. election and testified before the U.S. House Select Subcommittee regarding these recommendations. Prior to her position at WHO, she was the medical lead for COVID-19 vaccine rollout at the Medical University of South Carolina (MUSC) and helped coordinate vaccine education events for the staff and community and oversaw the reporting of adverse vaccine events.

Since joining WHO in August 2021, Dr. Kuppalli has been part of the WHO headquarters incident management team (IMST) for COVID-19, the clinical characterization and management working group for COVID-19, the COVID-19 therapeutics steering committee, and is the technical focal point for the post COVID-19 condition (Long COVID) steering committee. She is a member of the secretariat on the scientific advisory group on the origins of emerging and re-emerging infectious diseases (SAGO) which was convened by the Director General to understand and investigate the origins of SARS-CoV-2 and other novel pathogens. More recently since the development of the multi-country monkeypox outbreak she has been part of the IMST at WHO as one of the clinical management focal points. In this capacity she was part of the WHO core group that helped write the recently published Clinical Management and Infection Prevention and Control guidelines for Monkeypox and advising on the clinical endpoints for the global CORE therapeutics protocol.

Dr. Kuppalli is recognized as a scientific expert in global health, biosecurity and outbreak response. She was recognized by NPR Source of The Week early in the pandemic as an expert to follow and named to Elemental’s 50 Experts to Trust in a Pandemic. She has been a frequent contributor to numerous domestic and international media outlets including The New York Times, NPR, Reuters, The Washington Post, Vox, Stat News, San Francisco Chronicle, Forbes, NBC Bay Area, BBC News.