[James Thew/Adobe Stock]
While government agencies and international organizations are leading the charge on public health guidance, surveillance and research initiatives, private pharma firms are driving the development and manufacturing of H5N1 vaccines and antivirals, often in sync with academic institutions and with support from public funds.
Global efforts ramp up H5N1 pandemic preparedness
While the CDC has released interim guidance backing early antiviral treatment with oral oseltamivir (Tamiflu), inhaled zanamivir (Relenza), IV peramivir (Rapivab) or oral baloxavir (Xofluza), the effectiveness of these antiviral treatments for H5N1 specifically remains an open question. The agency acknowledges there are no clinical trial data from randomized clinical trials of antiviral treatment in patients with novel influenza A virus infection, but acknowledges positive outcomes from such trials in patients with seasonal influenza.
Oseltamivir (Tamiflu) and zanamivir (Relenza): The mainstays, but questions linger regarding pandemic potential
Questions regarding the potential of antivirals for pandemic influenza have persisted for years. In 2014, the charitable organization Cochrane reported modest symptom reduction from oseltamivir and zanamivir for seasonal influenza, but found no evidence of reduced complications, alongside an increased risk of adverse effects. As a result, some experts have questioned the rationale behind earlier stockpiling recommendations made by regulatory bodies in the 1990s and early 2000s.
More recently, experts have highlighted the importance of early antiviral treatment, particularly for high-risk groups, in reducing symptom duration, complications, hospitalizations and mortality associated with influenza. A 2021 network meta-analysis found that zanamivir was associated with the shortest time to alleviation of influenza symptoms compared to other antivirals and placebo, while baloxavir was associated with a lower risk of influenza-related complications. These findings underscore the potential benefits of antiviral medications in managing influenza, especially when administered within 48 hours of symptom onset.
Key players in H5N1 preparedness
The table below provides a snapshot of some notable players involved in H5N1 preparedness, outlining their roles, technologies, notable collaborations and ongoing clinical trials.
Entity |
Role in Pandemic Preparedness |
Product/Approach |
Technology |
Collaborations |
Testing/Guidance |
|---|---|---|---|---|---|
| CDC, WHO | Provide guidance on antiviral treatment for pandemic influenza, including novel avian influenza A viruses | Antiviral treatment recommendations | Neuraminidase inhibitors (oseltamivir, zanamivir, peramivir), cap-dependent endonuclease inhibitor (baloxavir) | – | CDC interim guidance recommends early antiviral treatment with oral oseltamivir (Tamiflu), inhaled zanamivir (Relenza), IV peramivir (Rapivab) or oral baloxavir (Xofluza) for outpatients and hospitalized patients with suspected, probable or confirmed novel influenza A virus infections associated with severe disease. |
| CSL Seqirus + GSK | Licensed Audenz H5N1 vaccine and ongoing trials. Adjuvant usage in vaccines has shown potential to reduce antigen doses needed. | Studies suggest fractional doses with adjuvants like MF59 may be effective, such as a 7.5 microgram dose producing a protective response in some adult populations, STAT has reported. | MF59 adjuvant, cell-based antigen manufacturing. Demonstrates effectiveness in generating protective antibody levels with reduced antigen amounts. | Collaboration with GSK, BARDA. Part of the National Pre-Pandemic Influenza Vaccine Stockpile (NPIVS). | CSL Seqirus is conducting a small human trial of an mRNA pandemic flu vaccine tailored to the new H5N1 2.3.4.4b subtype in the first half of 2024. The company aims to rapidly ramp up production if needed, potentially delivering tens of millions of doses within four to five months. |
| Sanofi | Major flu vaccine producer with a significant role in pandemic preparedness, developed the first licensed H5N1 vaccine in the U.S., and continues to expand capabilities for rapid pandemic response. | Fluzone High-Dose Quadrivalent, Flublok Quadrivalent, H5N1 avian influenza vaccine | Recombinant protein-based, egg-free (Flublok); involves recombinant technology for pandemic vaccines. | Collaboration with BARDA, significant investment in manufacturing capabilities for rapid production of pandemic vaccines. | Licensed the first H5N1 avian influenza vaccine for humans in the U.S. in 2007. In 2023, broke ground on a new facility to enhance pandemic flu vaccine production using both recombinant and adjuvant technologies. Has also explored the potential for mRNA flu vaccines, but has gone “back to the drawing board” on those efforts. |
| Pfizer | Developing a quadrivalent modified RNA (modRNA) vaccine for seasonal influenza. Pfizer and its partner BioNTech area also developing an mRNA-based combination vaccine candidate for influenza and COVID-19. | mRNA-based influenza vaccine | mRNA technology | Collaboration with BioNTech | Pfizer’s Phase 3 trials of its mRNA-based seasonal flu vaccine met primary goals, indicating efficacy in preventing influenza with a safety profile comparable to standard vaccines. Pfizer indicates that its influenza vaccine showed immune system reactions against H5N1 that were comparable to those produced by conventional flu vaccines. |
| Moderna | Developing mRNA flu vaccines, advancing rapid vaccine development for pandemic preparedness. | H5N1 vaccine from 2.3.4.4b subset | mRNA technology | – | Moderna is actively testing its mRNA-based H5N1 vaccine in human trials, targeting the 2.3.4.4b subset known for its pandemic potential. The company is also engaged in the CEPI’s 100 Days Mission to enhance rapid response capabilities using mRNA technology.
Moderna has a trial underway for an H5N1 flu vaccine candidate called mRNA-1010. It intends to file for regulatory approval later in 2024. |
| St. Jude | Has an initiative to combat avian influenza | Provided genetic material for TROVAC AIV H5 and Poulvac FluFend H5N3 RG vaccines. | Genetic material sharing, plasmid rescue system and technology licensing | Provided genetic material for TROVAC AIV H5 and Poulvac FluFend H5N3 RG vaccines. Contributed the H5 hemagglutinin (HA) gene to Virogenetics for the development of TROVAC AIV H5. Collaborations with Virogenetics (now part of Sanofi) and Fort Dodge Animal Health (a division of Wyeth, later acquired by Pfizer). | St. Jude has been instrumental in the development of avian influenza vaccines, sharing technology that led to the creation of vaccines like TROVAC AIV H5 and Poulvac FluFend H5N3 RG. These contributions stem from decades of research into avian flu, with licensing agreements that have led to the distribution of vaccines globally. |
| University of Pennsylvania | Developing multi-strain and single-strain mRNA flu vaccines including H5N1 | 20-subtype mRNA flu vaccine, single-strain mRNA H5N1 vaccine | mRNA technology | Drew Weissman’s lab at the University of Pennsylvania, has partnered with BioNTech, Moderna, Chulalongkorn University and internal Penn colleagues including Scott Hensley’s lab. | Engaged in pre-clinical testing of a single-strain mRNA H5N1 vaccine in animal models, aiming to broaden flu vaccine efficacy across multiple flu virus subtypes, including pandemic strains. |
| University of Washington | Developing a universal flu vaccine using DNA technology and a novel delivery method to provide broad protection against diverse influenza strains, including H5N1. | Universal flu vaccine using a “gene gun” device to deliver DNA vaccines encoding conserved flu antigens | DNA vaccine technology with a “gene gun” delivery device | Collaborating with the National Institutes of Health (NIH) on developing a universal flu vaccine using mRNA technology. | The University of Washington researchers are using a “gene gun” device to deliver DNA vaccines encoding conserved flu antigens along with an immune stimulant. This dry powder vaccine can be stored at room temperature, making it suitable for low-resource regions. The gene gun approach has shown effectiveness against various human, avian, and swine flu strains in animal studies. Clinical trials are planned to evaluate its efficacy in humans. |
| Duke University | Engaged in developing broadly reactive influenza vaccines, including against avian influenza. | Universal influenza vaccines, including coverage against avian strains | Influenza program at the Duke Human Vaccine Institute, CIVICs program partnership | Duke Human Vaccine Institute (DHVI), Institutional Biosafety Committee (IBC) | Part of NIAID’s CIVICs program aiming for durable protection against influenza; conducts iterative vaccine design, preclinical studies, and early-phase clinical trials. Duke’s IBC ensures stringent biosafety and compliance with NIH guidelines for handling pathogenic agents. |
| NIAID | Leading research for a universal influenza vaccine; conducting trials for several vaccine candidates. | H1ssF-3928 mRNA-LNP, FluMos-v2 nanoparticle vaccine | mRNA technology, nanoparticle technology | Collaborative Influenza Vaccine Innovation Centers (CIVICs), various universities, NIH Clinical Center | In 2023, NIAID initiated Phase 1 trials for H1ssF-3928, an mRNA universal flu vaccine, and FluMos-v2, a nanoparticle vaccine aiming to protect against multiple flu strains. The trials assess safety, immunogenicity, and potential for long-lasting protection against diverse influenza strains. |
Filed Under: clinical trials, Drug Discovery, Immunology, Infectious Disease, Regulatory affairs
