This episode of "This Week in Virology" discusses two primary scientific papers: a meta-analysis on the therapeutic use of the HPV vaccine and a study on monoclonal antibodies for mpox treatment.
The first segment analyzes a meta-analysis published in Viruses, which consolidates findings on vaccinating HPV-positive adult women with Gardasil-9. The hosts discuss the surprising and significant results showing that the vaccine, traditionally used for prevention, has therapeutic benefits. It is shown to aid in the clearance of existing HPV infections, reduce the progression of precancerous cervical lesions (SIL/CIN), and lower the rate of lesion recurrence following surgical excision.
The second half of the podcast delves into a paper from Cell detailing the isolation and characterization of human monoclonal antibodies against the monkeypox virus (mpox). These antibodies target the A35 protein, a component of the extracellular enveloped virion responsible for cell-to-cell spread. The study demonstrates that these antibodies protect mice from lethal infection both prophylactically and therapeutically. Structural analysis reveals they bind to a highly conserved groove on the A35 protein, suggesting their potential as a broad treatment for orthopoxviruses. The discussion also touches on the practical challenges of antiviral timing in a clinical setting.
TWiV 1267: A Deep Dive into HPV Vaccine's Therapeutic Potential and a Novel Mpox Treatment
5:53 Endangered Research Monkeys: The podcast begins with a news item about the International Union for Conservation of Nature (IUCN) upholding its classification of long-tailed macaques as an endangered species. The hosts discuss the ethical complexities and potential impact this will have on biomedical research, which uses these primates as models.
13:52 Mosquitoes Found in Iceland: A second news story highlights the first-ever reported discovery of a breeding mosquito population in Iceland. The hosts discuss the implications of this finding, attributing it to a warming climate and increased global transportation.
17:45 A Cancer Vaccine as a Treatment: The first major paper discussed is a meta-analysis evaluating the use of the Gardasil-9 HPV vaccine as a therapeutic agent in adult women who are already HPV-positive or have confirmed precancerous cervical lesions (Squamous Intraepithelial Lesions, or SIL).
19:08 Key Findings on HPV Vaccine's Efficacy: The analysis of seven studies, involving over 19,000 women, showed that vaccination was linked to significant benefits:
Viral Clearance: It increased the rate of complete HPV remission (disappearance of the virus), with up to 72% of vaccinated women clearing the virus compared to 45% of unvaccinated women.
Reduced Progression: It lowered the risk of precancerous lesions progressing to higher grades.
Prevents Recurrence: It significantly reduced the recurrence of high-grade lesions after surgical removal (conization), with the best results seen when the first vaccine dose was given before the procedure.
24:40 HPV Biology and Cancer: The hosts provide a background on Human Papillomavirus (HPV), explaining it's a small DNA virus that can cause cancer. The viral genes E6 and E7 can accidentally integrate into the host cell's genome, driving uncontrolled cell division that leads to cancer, most notably cervical carcinoma.
52:40 A Surprising Therapeutic Mechanism: The hosts express fascination that a vaccine designed to elicit an antibody response (Gardasil-9 consists of virus-like particles) can treat an established infection, a role typically associated with a cellular immune response. They draw a parallel to the rabies vaccine, another rare example of a post-infection therapeutic vaccine.
59:28 Antibodies to Treat Mpox: The second paper focuses on developing a treatment for mpox by isolating human monoclonal antibodies from a convalescent individual. These antibodies target the A35 protein.
1:01:22 Poxvirus Forms Explained: The hosts explain that poxviruses like mpox have two main infectious forms: the Intracellular Mature Virion (IMV), which is stable and responsible for host-to-host transmission, and the Extracellular Enveloped Virion (EEV), which is crucial for spreading the virus from cell to cell within an infected host. The A35 protein is on the surface of the EEV.
1:11:51 Antibodies Protect Against Lethal Disease: In mouse models, the isolated anti-A35 antibodies were highly effective.
They blocked viral spread in vitro, as measured by a "comet assay."
They protected mice from lethal doses of vaccinia virus and mpox virus when given before infection (prophylactically).
Crucially, they were also effective when administered 24 hours after infection (therapeutically), demonstrating their treatment potential.
1:23:31 Potent Neutralization and Fc Function: The antibodies were shown to work through multiple mechanisms. While they could engage in Fc-dependent functions like ADCC, they remained highly protective even when their Fc function was removed. This indicates a potent ability to directly neutralize the virus and inhibit its spread, a desirable trait for a therapeutic.
1:28:04 A Promising and Conserved Target: Structural analysis revealed that the antibodies bind to a highly conserved groove formed by the A35 protein dimer. Because this site is conserved across different orthopoxviruses, these antibodies could be developed into a broad-spectrum treatment.
1:33:40 The Challenge of Antiviral Timing: Rich Condit points out a critical challenge for any therapy that inhibits viral spread. By the time a patient presents with symptoms (e.g., mpox lesions), the virus has already been spreading systemically for days or weeks. This delay can limit the effectiveness of treatments like these antibodies or the drug tecovirimat, underscoring the universal importance of early intervention.