Objective 1: Strategic Implementation and Deployment of the U.S. National Pre-pandemic Influenza Vaccine Stockpile (NPIVS)
BARDA has established the Medical Countermeasures (MCMs) for Pandemic Influenza and Emerging Diseases Preparedness and Response Program, which includes administration of the U.S. National Pre-pandemic Influenza Vaccine Stockpile (NPIVS). The NPIVS contains pre-pandemic influenza vaccine, contracts with domestic vaccine manufacturers, and procures vaccine to mitigate the public health impact of emerging disease threats. Unlike seasonal influenza vaccines, pandemic vaccines are given to an immunologically naïve population (all age groups) that require two doses of an adjuvanted vaccine for protection; the first dose to prime the immune system and the second to boost the immune response. Adjuvant is required for egg-, cell- and recombinant protein-based vaccines to achieve antigen-sparing and robust protection.
Current Preparedness Activities
Stockpiled H5Nx Vaccines
The current NPIVS inventory includes several bulk lots of H5Nx antigen including for clade 2.3.4.4b, the clade responsible for the human cases in Colorado, Texas, and Michigan, as well as closely related 2.3.4.4a, c, f, and h clades. In 2022, BARDA awarded task orders to manufacture cGMP seed lots for egg-, cell- and recombinant protein-based vaccines for A/Astrakhan H5N8 and proactively manufacture A/American wigeon/SC H5N1 CGMP (cell-based) seed lot and bulk lot. As manufacturing and clinical testing remain significant bottlenecks in vaccine development, this advanced vaccine production has allowed rapid movement of these vaccines into clinical development. To further lean into preparedness for H5N1, BARDA finalized an agreement with CSL Seqirus in May 2024 to fill ~4.8 million additional doses of the bulk A/Astrakhan H5N8 vaccine into vials.
Clinical Trials
To generate the necessary clinical evidence to support regulatory approval, BARDA is currently supporting three clinical trials to evaluate vaccine candidates derived from A/Astrakhan H5N8: 1) a cell-based vaccine adjuvanted with MF59 from CSL Seqirus, 2) an egg-based vaccine adjuvanted with AS03 from GlaxoSmithKline (GSK), and 3) an egg-based vaccine from Sanofi adjuvanted with either AS03 or MF59. The trials for CSL Seqirus and GSK are fully enrolled, while the trial for Sanofi will begin in Summer 2024 with safety data expected by Q4 2024.
Future Research Priorities
Expanded Capabilities – Immune Assays
To rapidly respond to the emergence and spread of new strains of influenza virus or emerging infectious diseases with pandemic potential, capacity for rapid development, qualification, and validation of immunogenicity assays to support clinical trials that ensure pandemic readiness are needed. To achieve this, BARDA also seeks to partner with laboratories with existing capabilities to perform centralized immune assays using samples collected from nonclinical studies and from subjects enrolled in influenza vaccine clinical trials conducted under the U.S. Food and Drug Administration (FDA) Investigational New Drug (IND) applications and to perform cross-reactive immune response testing of clinical samples for pandemic preparedness and response. Data from these assays may be used in primary, secondary, and exploratory endpoint analyses for vaccine clinical trials, cross-reactivity testing for pandemic readiness purposes, or perform correlates of protection analyses. Data may be used to support an FDA Emergency Use Authorization (EUA) or a Biological License Application (BLA).
Expanded Stockpile Capabilities – mRNA-based vaccines for pandemic influenza response
The mRNA vaccine platform has unique advantages compared to current egg-, cell- and recombinant protein-based vaccines due to the short period of time needed for development and manufacturing of a vaccine against a novel virus. From the availability of the genetic sequence for a target antigen from an emerging pathogen, it takes only 14 weeks for an mRNA-based vaccine to be put into large-scale production. In particular, mRNA-based vaccine platforms can be switched to a new viral strain swiftly, which is an important attribute when responding to a new influenza strain that emerges and spreads rapidly. Finally, pandemic and seasonal influenza mRNA vaccines have identical supply chains whereas for egg-, cell- and recombinant protein-based vaccines require adjuvant components that are not widely used in seasonal influenza or other licensed vaccines, posing major challenges to the sustainability pandemic influenza vaccine preparedness programs.
Currently, there is no licensed mRNA influenza vaccine for either seasonal or pandemic influenza. Since 2020, BARDA has funded development of several RNA-based influenza vaccine candidates, and in late 2023, BARDA released a solicitation “Accelerating Near-Term Availability of mRNA-based Pandemic Influenza Vaccine,” which seeks to partner with companies to fill the mRNA vaccine gap for influenza virus. In the future, BARDA will seek to incorporate licensed mRNA-based pandemic influenza vaccines for influenza viruses of pandemic potential, e.g., H5Nx and H7Nx, into the NPIVS, adding a more rapid option to the arsenal for the nation’s pandemic influenza preparedness and response.