Influenza Vaccines: Didactics, Debates, and Developments

Every year, thousands of Canadians become infected with the influenza virus. At October’s IIDR Combined Joint Rounds, Dr. Mark Loeb and Dr. Matthew Miller reflect on how studying the virus at both a cellular and population-level can lead to valuable conclusions to help mitigate influenza epidemics.

Dr. Loeb began the seminar with a presentation on seasonal influenza vaccination trends over the last decade. Notably, following the 2009 H1N1 pandemic, controversy arose over the relative effectiveness of the live attenuated influenza vaccine (LAIV) and the inactivated influenza vaccine (IIV). It had first been suggested that LAIV was more effective than IIV, resulting in the preferential recommendation of LAIV, especially in children. However, in 2016, the CDC stopped recommending LAIV due to concerns over its apparent decreased effectiveness in comparison to IIV. Over the course of 3 influenza seasons from 2012 to 2015, Dr. Loeb conducted randomized blinded control trials in children of Hutterite colonies to explore this issue more conclusively and concluded that there was no significant difference between LAIV and IIV in offering protection against influenza. This CIHR-funded study is particularly meaningful as it used superior methodology when compared to the data used by the CDC to make its recommendation against using LAIV.

Dr. Loeb further presented the significant findings of another study, conducted with his MSc student Jessica Bartoszko on the impact of consecutive influenza vaccination. The team performed a meta-analysis of randomized controlled trials and observational studies to conclude that repeat seasonal vaccination does not reduce the effectiveness of current annual vaccination strategies.

Such epidemiologic and population-based studies are essential in shedding light on more efficient ways to reduce the community burden of influenza infection. Dr. Loeb hopes to continue conducting epidemiological studies in larger areas to further assess the efficacy of other widely available vaccines.

Dr. Miller followed Dr. Loeb with a discussion on how taking a closer look at the immunological properties of past influenza pandemics has led to novel avenues for vaccine development.

Dr. Miller first explained how current vaccinations against influenza virus are designed to stimulate the production of antibodies that neutralize the head of hemagglutinin surface proteins on the influenza virus. However, because the RNA genome of influenza A viruses (IAV) are highly susceptible to both rapid mutation and reassortment, these surface proteins change frequently, resulting in the need for new vaccinations to be developed each year. These reformulations depend on predictions of which viral strains may circulate in the upcoming season. In consequence, influenza infection still remains a prominent source of global illness.

Dr. Miller went further to explain how he and his colleagues were able to find innovative ways to overcome the limitations of seasonal vaccinations. In one study, the team found that the blood samples of human populations who were exposed to previous pandemics – such as the H3N2 pandemic in 1968 and the H1N1 pandemic in 2009 – contained higher levels of a unique group of antibodies. These antibodies were found to bind to the stalk of the HA surface protein, which unlike the globular head, does not tolerate mutation. In turn, Dr. Miller’s team concluded that exposing the immune system to antigenically divergent HAs similar to those found in pandemics can generate similar stalk-binding antibodies, leading to efficient protection across a wide range of IAV subtypes.

By further investigating how to successfully recruit white blood cells to destroy the viruses neutralized by these antibodies, Dr. Miller and his colleagues at McMaster University (Ontario), the Icahn School of Medicine at Mount Sinai (New York) and the University of Chicago (Illinois) were able to further inform the development of a “universal vaccine”. This vaccine, which is currently entering clinical trials, would protect against a wide variety of IAV strains, including future mutated subtypes, and would not need to be taken annually.

Dr. Loeb and Dr. Miller’s innovative studies reiterate the importance of multidisciplinary research in the fight against infectious disease. Through the IIDR’s principles of innovation, high-risk, high-reward research, and cross-collaboration, these leaders are paving the way for the future of healthcare.

IIDR Combined Joint Rounds are presented on the first Wednesday of every month at the McMaster University Medical Centre and are open to all IIDR members and trainees.