By JCVI Staff

COVID-19 Further Complicating Flu Season

While the world is rightly focused on the ongoing COVID-19 pandemic, it’s important to know that influenza is always a significant public health burden, and the combination of the pandemic and flu season could converge to become a perfect storm of infectious diseases.

Influenza causes 3 to 5 million cases of severe illness and 300,000 to 500,000 deaths worldwide each year. Vaccination is still the best and often, only method in preventing infection and disease. Flu vaccines are aimed at preventing us all from getting sick, reducing the severity of illness, and decreasing the chance of spreading the disease to vulnerable individuals. However, despite vaccines and supportive medical interventions such as antivirals and antibiotics, influenza remains a public health problem that can be deadly for the very young, the elderly, and the immune compromised. These are the same populations who are also more at risk for COVID-19.

Gene Tan, Ph.D., assistant professor in JCVI’s Infectious Disease Group, is leading a project to construct a new type of RNA-based flu vaccine using synthetic biology techniques. The process involves delivering a self-replicating RNA platform that delivers pieces of the flu virus into cells via a fusogenic particle which can elicit a long-lived immune response comparable to a live attenuated vaccine (LAIV), and is superior to inactivated or protein-based vaccines.

Flu vaccines are typically inactivated vaccines and thus require annual reformulations to optimally protect against the latest strains. The majority of pharmaceutical companies still rely on the decades-old method of manufacturing influenza vaccines in embryonated chicken eggs, which poses two potential problems - individuals with egg allergies  cannot receive the vaccine and a large number of eggs (i.e., one to two eggs per dose) and a long lead time are required to manufacture influenza vaccines. The untimely distribution and administration of the H1N1 vaccine during the 2009 pandemic was a good example of the weakness of this current workflow.

The  immune response elicited by inactivated influenza vaccines (IIV) wanes in six to eight months after immunization, while immunity is maintained up to a year following LAIV administration. The latter, however, is contraindicated for the immunocompromised, pregnant women and the very young. Dr. Tan’s new approach combines the safety features of an inactivated influenza vaccine, with the immune responses elicited by a LAIV. RNA is also arguably more cost-effective and faster to manufacture. The replicon is also genetically modular and easy to manipulate.

Dr. Tan is also studying how modulation of innate immune cells, particularly alveolar macrophages, which are involved in antibody-mediated processes impacts immunity. Induction of antibodies against influenza A virus is a major factor in protection. Prior published works demonstrate that broadly protective antibodies require interactions with innate immune cells to work optimally to control and clear virus replication in vivo. Understanding the basis of how innate immune cells and antibodies work together will help in revealing pathways to exploit during vaccination or immunotherapy.