The 1918 Spanish flu pandemic was one of the deadliest in human history, claiming an estimated 20-100 million lives worldwide. Despite its devastating impact, the genetic makeup of the virus responsible for this pandemic had remained a mystery – until now.

Researchers from the University of Basel and Zurich have successfully reconstructed the genome of the influenza virus that ravaged Europe during the first wave of the pandemic in Switzerland. The study, led by paleogeneticist Verena Schünemann, used a 100-year-old specimen taken from an autopsy sample of an 18-year-old patient who died in July 1918.

The researchers identified three key adaptations that allowed the virus to spread and persist throughout the pandemic. These mutations made the virus more resistant to human immune system defenses, allowing it to bind more efficiently to human cells and increasing its infectiousness.

This breakthrough study has significant implications for tackling future pandemics. By understanding how viruses adapt and evolve over time, scientists can develop targeted countermeasures and improve public health responses. The researchers emphasize the importance of medical collections as archives for reconstructing ancient RNA virus genomes and highlight the need for further reconstructions to inform models for future pandemics.

The study’s authors stress that their interdisciplinary approach, combining historico-epidemiological and genetic transmission patterns, provides an evidence-based foundation for calculations and will be crucial in developing targeted strategies for addressing future pandemics.

The researchers analyzed 293 blood and tumor samples from 72 patients with non-small cell lung cancer, obtained at different times throughout their treatment journey. They used multiomic analyses to deeply characterize the immune system’s response to radiation therapy followed by immunotherapy. The team focused on immunologically “cold” tumors, which typically don’t respond to immunotherapy.

The study revealed that radiation can stimulate a systemic anti-tumor immune response in lung cancers, making them more responsive to treatment. The researchers found that patients who received radiation and immunotherapy had better outcomes than those who didn’t receive radiation therapy. They also confirmed that the T cells expanding in patients who received radiation and immunotherapy were indeed recognizing specific mutation-associated neoantigens from their tumors.

This breakthrough has significant implications for cancer treatment, particularly for patients with non-small cell lung cancer who don’t respond to immunotherapy. The researchers hope that this study will lead to the development of new treatments that combine radiation therapy with immunotherapy to improve patient outcomes.

The study was supported by the Johns Hopkins Bloomberg~Kimmel Institute for Cancer Immunotherapy and the National Institutes of Health. Additional co-authors on the study include various researchers from the Netherlands Cancer Institute, Radboud University Medical Center, and other institutions.

The lead author of the study, Dr. Valsamo Anagnostou, notes that this research highlights the importance of international, interdisciplinary collaboration in translating cancer biology insights to clinical relevance. She also emphasizes the value of this study in capturing the abscopal effect, linking the immune response with clinical outcomes, and confirming the body’s response to immunotherapy by detecting circulating tumor DNA (ctDNA) in the blood.

This research has significant potential for advancing cancer treatment and improving patient outcomes. As researchers continue to explore the benefits of combining radiation therapy with immunotherapy, they may uncover even more effective treatments for various types of cancer.

A groundbreaking study co-led by Australian researchers has shed new light on the life-threatening virus HTLV-1, which affects around 10 million people globally. Despite its prevalence, HTLV-1 remains a poorly understood disease with no preventative treatments or cure. However, the research team, comprising experts from WEHI and the Peter Doherty Institute for Infection and Immunity (Doherty Institute), has made significant strides in understanding the virus’s behavior and identifying potential therapeutic targets.

The study, published in Cell, found that existing HIV drugs can suppress the transmission of HTLV-1 in mice. This promising result could lead to the development of the first treatments to prevent the spread of this virus, which is endemic among many First Nations communities around the world, including Central Australia.

According to co-lead author and WEHI laboratory head Dr Marcel Doerflinger, “Our study marks the first time any research group has been able to suppress this virus in a living organism.” This achievement paves the way for further investigation into using HIV drugs as a pre-exposure prophylaxis against HTLV-1 acquisition.

The researchers also isolated the virus and developed a world-first humanized mouse model for HTLV-1, which enabled them to study how the virus behaves in a living organism with a human-like immune system. This breakthrough allowed the team to understand how different strains of the virus can alter disease symptoms and outcomes.

The study’s lead author, Professor Marc Pellegrini, emphasized that “the development of the humanized mouse models was not only critical in identifying potential therapeutic targets but also allowed researchers to understand how different strains of the HTLV-1 virus can alter disease symptoms and outcomes.”

In another remarkable finding, the team discovered that human cells containing HTLV-1 could be selectively killed when mice were treated with HIV drugs in combination with another therapy inhibiting a protein (MCL-1) known to help rogue cells stay alive. This discovery has significant implications for developing new treatments for HTLV-1.

The research team is currently in talks with the companies behind the HIV antivirals used in this study, to see if HTLV-1 patients can be included in their ongoing clinical trials. If successful, this would pave the way for these drugs to become the first approved pre-exposure prophylaxis against HTLV-1 acquisition.

The findings of this study are supported by The Australian Center for HIV and Hepatitis Virology Research, The Phyllis Connor Memorial Trust, Drakensberg Trust, and the National Health and Medical Research Council (NHMRC). These organizations recognize the importance of continued research into understanding and combating HTLV-1.