Objective 2: Enhanced Protection – Improved Vaccines against Pandemic Influenza 

BARDA seeks to advance novel vaccines for pandemic influenza that can maximize protection during a future outbreak or pandemic. Improved vaccines for pandemic influenza may incorporate multiple characteristics, such as providing early protection in advance of an outbreak, being rapidly deployable in the event of an outbreak, and/or providing easier distribution and administration through alternative, non-needle-based delivery systems. 

Current Preparedness Activities

RNA vaccine development programs

In partnership with the Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND) in the Department of Defense (DOD), BARDA is advancing three self-amplifying RNA (saRNA) vaccine candidates for H5Nx influenza. saRNA vaccines may require lower doses and provide a longer-lasting immune response, making them appealing as a potentially more scalable RNA-based vaccine technology. One partner, the Access to Advanced Health Institute (AAHI), is developing a bivalent H5N1/H7N9 saRNA vaccines for both intramuscular and intranasal administration. A second partner, AstraZeneca, is developing a bivalent H5N1/H7N9 saRNA vaccine for intramuscular and/or transdermal patch administration. The third partner, Arcturus Therapeutics, is developing a saRNA vaccine for H5N1 for intramuscular administration. All of these vaccine candidates are in preclinical development.

Alternative Delivery

A key element in executing a mass immunization campaign during a public health emergency is having the capability to administer the vaccine to the entire population. Current vaccination strategies, almost all require injection of a liquid via needle and syringe, place a tremendous burden on the healthcare system and supply chain, especially during a pandemic. Novel alternative delivery systems such as oral, intranasal, transdermal, and subcutaneous microarray patches (MAPs) offer several advantages over the injectable preparations, including the potential for rapid delivery, ease of administration and improved vaccine performance. These novel vaccination delivery systems have the potential to increase antigen stability and improve overall immunogenicity as well. BARDA is partnering with companies to advance needle-free vaccine technologies, some of which may induce mucosal immunity. BARDA currently supports Vaxxas, which is developing an adjuvanted vaccine for pandemic influenza with a high-density patch. BARDA is also supporting Vaxess and their microneedle patch technology in partnership with AstraZeneca’s pandemic influenza saRNA vaccine under development.

The Project NextGen Enable program is spurring innovation in vaccine formulation and administration by using a prize competition to reward developers that are first to achieve key development goals. In the first competition, BARDA aims to advance patch-based delivery of RNA vaccines for COVID-19, pandemic influenza, and/or seasonal influenza into clinical testing. The second competition aims to reduce the number of primary series doses needed for protection to a single shot and will leverage pandemic influenza as a model. These approaches complement the ongoing influenza patch development effort, with the potential to improve efficacy and accessibility of not just COVID-19 and pandemic influenza vaccines, but a broad range of mRNA-based vaccines. 

Advancing Decentralized Clinical Trial Capabilities for Vaccine Studies

Project NextGen is also approaching accessibility from the perspective of enabling more robust vaccine correlate of protection studies. BARDA is supporting decentralized clinical trials (DCTs) where various trial elements, like clinical sample collection and symptom monitoring, will occur either in the home or at a retail pharmacy location. Using DCTs to reduce the participation barrier has the potential to increase the breadth and diversity of participants and improve accessibility. BARDA is also advancing development of an algorithm that uses data collected from wearable fitness devices to identify asymptomatic/pre-symptomatic respiratory virus infection (COVID-19, Influenza A, Influenza B, and/or RSV). These envisioned capabilities enable the critical link between sample collection for immune analysis and correlation with infection, which will be a key component of preparing for and responding to an influenza pandemic.

Future Research Priorities

Enhanced Protection: Broadly Protective Vaccines

Vaccines that could be deployed before an outbreak begins and provide immune responses to a broad range of influenza viruses could enable the population to have some level of protection against H5Nx viruses prior to a pandemic. Incorporating broadly conserved immunogens into existing seasonal vaccines could provide some improved seasonal influenza protection but would critically have the additional benefit of enhancing immunity to pandemic influenza in the population so that individuals are protected from severe disease and death before a matched vaccine is deployed. These vaccines could also be explored for their ability to delay spread. BARDA currently supports Janssen’s mini-HA stem-based recombinant protein influenza vaccine, which targets the conserved HA-stem region of influenza A viruses. BARDA seeks development of supra-seasonal vaccines to mitigate the impact that any influenza pandemic would have during the time needed to develop and deploy a matched vaccine, decreasing severe disease and death for the entire population and potentially delaying incidence and spread.