Many experts consider another influenza pandemic to be inevitable. Influenza virus subtype H5N1, lethal to birds, mammals and humans, is being closely monitored for its pandemic potential. Vaccines against influenza H5N1 have been developed. But the virus is constantly evolving, and new vaccine approaches are needed to ensure readiness and protection.

DelNS1 H5N1, a nasal spray vaccine in clinical development, generates an immune response that’s both quantitatively and qualitatively better than the response induced by the intramuscular shots for pandemic flu. Clinical studies show that a single dose of DelNS1 H5N1 achieves a serum antibody response (seroconversion) accepted by regulators as predictive of clinical benefit. Licensed pandemic vaccines require two doses to mount a comparable response.

The DelNS1 H5N1 immune response is qualitatively better because it recruits multiple arms of the complex immune response against multiple influenza virus targets. DelNS1 H5N1 induces antibodies in the linings of the nasal passages - creating a first line of defense at invading viruses’ point of entry, plus serum antibodies and T cells important in clearing the virus infection, enhancing the immune response, and enabling long-lasting protection. Available pandemic flu shots generate a comparatively narrow immune response, consisting of serum antibodies against a single target on a specific influenza virus strain.

DelNS1 H5N1 is well suited for use in the event of a pandemic. Immunization by nasal spray requires minimal training and is amenable to mass administration campaigns and even self-administration. Needle-free immunization also mitigates vaccine hesitancy, avoids the hazards of sharps handling and disposal, and side-steps significant issues of supply chain disruptions and shortages of syringes and needles that can cripple immunization programs.

A pandemic flu vaccine that blocks transmission would be unprecedented, providing a major advance in reducing disease spread and bringing the pandemic to an end. DelNS1 vaccines have been shown to block transmission of a wide range of influenza viruses in animal models.

Shots specifically matched to a pandemic strain are the standard of care, but developing and producing a strain-matched pandemic vaccine takes time. Data suggest that if deployed at the onset of a pandemic, a single dose of DelNS1 H5N1, with its broad immune response, could protect vulnerable individuals and populations no matter which particular influenza virus variant emerges to ignite a pandemic.

Used before or at the onset of a pandemic, DelNS1 H5N1 conceivably could block transmission, dampen the pandemic, and buy time for development of vaccines closely matched to the novel pandemic strain. DelNS1 H5N1 could be stockpiled and ready for use as an off-the-shelf priming dose before availability of a strain-matched vaccine, increasing the efficacy of an evenutal strain-matched vaccine, and cutting the need for strain-matched doses in half. Considering the need for hundreds of millions of doses that would be required in a pandemic, this dose-sparing benefit is a huge advantage in protecting the population. Our planned Phase 2 study will evaluate immunogenicity and safety of DelNS1 H5N1 as both a stand-alone, single-dose vaccine and as a prime vaccine followed by either a strain-matched shot or a second dose of DelNS1 H5N1.