This episode of This Week in Virology (TWiV) discusses several current events and scientific papers. Key news items include concerns over Vinay Prasad's appointment as the new CBER chief at the FDA, the Gates Foundation's plan to conclude its operations by 2045 after disbursing its wealth, and a new executive order imposing restrictions on "dangerous gain of function research," which the hosts critique for its premises and potential impact on science. The podcast then delves into two scientific papers. The first, published in Cell, investigates the origins of bat viruses ancestral to SARS-CoV and SARS-CoV-2, suggesting recent emergence from bat populations (1-6 years prior to human outbreaks) and implicating wildlife trade in their spread to human emergence sites, far from their likely ancestral locations. The second paper, from Nature Communications, details a single-dose Sudan virus replicon RNA vaccine using a novel LION nanocarrier, which demonstrated 100% protection in guinea pigs. The episode also features listener emails on various topics, including rabies vaccination for veterinarians and the challenges of science communication in the current political climate.
TWiV 1217: Discussions on New FDA Leadership, Pandemic Origins, and a Novel Sudan Virus Vaccine
0:00 Introduction & Host Updates: The hosts introduce the episode, discuss current weather conditions, and Rich Condit mentions a non-SARS-CoV-2 respiratory pathogen he's experiencing.
2:03 Respiratory Pathogen Panels: A listener letter prompts discussion about comprehensive PCR panels (e.g., BioFire) that can identify a wide range of respiratory pathogens beyond just SARS-CoV-2, highlighting a case of metapneumovirus.
4:56 Call for Support: Vincent Racaniello emphasizes MicrobeTV's non-profit, ad-free model and the importance of listener support for science communication, especially when science is under attack.
6:23 New CBER Chief V. Prasad: The hosts express significant concern over Vinay Prasad's appointment as the new CBER (Center for Biologics Evaluation and Research) chief at the FDA, replacing Peter Marks. They criticize Prasad's past statements on COVID-19 measures and the drug industry, fearing negative impacts on vaccine standards and regulatory predictability.
11:56 Gates Foundation to End by 2045: Discussion on the Gates Foundation's announcement that it will spend its remaining wealth and cease operations within the next 20 years (by 2045). Bill Gates' aspirations for global health are highlighted.
16:15 Executive Order on Gain of Function Research: The hosts critique a new executive order restricting "dangerous gain of function research." They find fault with its definitions, the underlying implication that SARS-CoV-2 was a lab leak, its political nature, and its potential to stifle important scientific research through top-down regulation and funding restrictions.
22:25 Smallpox Eradication Anniversary: A brief mention of the 45th anniversary of the declaration of smallpox eradication.
24:14 Paper on Bat Virus Origins of SARS-CoV & SARS-CoV-2:
25:02 Study Overview: Alan Dove introduces a Cell paper by Pecar et al. analyzing available viral sequence data (considering recombination) to determine the recency and geographical origins of bat viruses ancestral to SARS-CoV-1 and SARS-CoV-2.
26:51 Key Findings: The study suggests both viruses descended from distinct horseshoe bat coronaviruses that circulated 1-6 years before their respective emergences in humans.
27:11 Wildlife Trade Implication: The immediate ancestors of both viruses likely reached human emergence sites (Wuhan for SARS-CoV-2, Guangdong for SARS-CoV-1) much faster than typical bat dispersal rates, strongly implicating the wildlife trade in their movement.
30:02 Methodological Innovation: The study focused on non-recombining regions (NRRs) of the viral genomes to more accurately calibrate molecular clocks, estimating SARS-CoV-1's closest inferred bat ancestor to have circulated around 1996-2001 and SARS-CoV-2's around 2014.
43:32 Geographic Origins: Ancestors of SARS-CoV-1 likely circulated in western China (Yunnan, Sichuan, Guizhou), while SARS-CoV-2 ancestors were in Yunnan or northern Laos, both over 1000 km from their human emergence points.
50:01 Conclusion: The findings support a natural origin and zoonotic spillover facilitated by human-mediated animal transport, countering lab-leak theories.
54:11 Paper on Single-Dose Sudan Virus Replicon Vaccine:
54:17 Study Overview: Alan Dove introduces a Nature Communications paper on a single-dose Sudan virus replicon RNA vaccine. Sudan virus is a deadly Ebola virus species with no currently approved vaccines.
55:33 Replicon and LION Technology: The vaccine uses a self-amplifying RNA (replicon) delivered via a LION (Localizing Cationic Nanocarrier) formulation, where RNA is adsorbed to the surface, aiming for lower reactogenicity and single-dose efficacy.
1:05:10 Guinea Pig Study Results: A single dose of the LION-Sudan virus vaccine provided 100% protection against disease and death in guinea pigs challenged with Sudan virus three weeks post-vaccination. This was superior to a VSV-Sudan vaccine candidate in the same study.
1:09:10 Immune Response: The LION-Sudan vaccine significantly reduced viral load in blood, liver, and spleen, and minimized tissue pathology. Protection involved both neutralizing antibodies and Fc-mediated effector functions.
1:15:27 Rabies Vaccination for Vets: Multiple listeners (veterinarians) confirm that rabies vaccination (often a two-dose primary series with titer checks) is standard and typically mandatory for veterinary students in both the US and Canada.
1:17:21 Oprah's Endorsements: A listener questions if Oprah Winfrey has expressed regret for promoting figures like Dr. Phil and Dr. Oz.
1:19:29 Motivations Behind Current Political Climate: A listener suggests racism and misogyny as key drivers, which Rich Condit links to the "three poisons" of greed, hatred, and delusion.
1:23:59 Science Communication in Politicized Times: A listener praises TWiV for continuing science communication under difficult circumstances and acknowledges that remaining apolitical is a privilege lost when science itself is attacked.