Preliminary CDC estimates of influenza burden in the US during the 2019–2020 season remain high, as it was for the 2016–2017, 2017–18, and 2018–2019 seasons. With over 2 million confirmed cases worldwide, COVID-19 is a public health emergency warranting international attention. However, influenza continues to be a significant public health threat with an estimated 49 million illnesses, 23 million medical visits, 620,000 hospitalizations, and 52,000 deaths in the US alone between October 2019 and February 2020.

While the public health impacts of influenza are substantial, vaccination rates remain low, plateauing around 60% over the course of the last 5 influenza seasons, having peaked at 63% during the 2018–19 season among children 6 months through 17 years. Although the number of COVID deaths continue to rise, 8,100 influenza-associated deaths occurred among working age adults during the 2018–19 season, when vaccination rates were considerably lower at 45.3%.

Misconceptions a Barrier to Vaccine Uptake

Misconceptions about the influenza vaccine may be a key barrier to vaccine uptake from season to season, particularly among adults ages 18–64. A variety of misconceptions may impact overall vaccine confidence and decrease the perceived value of influenza vaccination. These misconceptions pertain to:

• Vaccine effectiveness: There is a misconception that influenza vaccination is ineffective because the CDC estimates that vaccine effectiveness for the 2019–2020 season is around 45% (this figure may vary by age group). However, vaccine effectiveness has been as high as 60% when the vaccine strains are well matched to the circulating viruses. It is not the case that influenza vaccines are inherently ineffective but rather that they may be ineffective when strain drift occurs throughout the season. Thus, in some cases, vaccinated persons may still get the flu not because the vaccine itself was ineffective but rather because a different strain was the cause of infection. Vaccination remains the most effective way of preventing infection.
• Herd immunity: Vaccination maintains herd immunity, the indirect protection from infectious diseases, and protects particularly vulnerable populations, including infants, older adults, persons with chronic conditions, and those who are immunocompromised from severe infection. Currently, the Advisory Committee on Immunization Practices (ACIP) recommends routine influenza vaccination for all persons above the age of 6 months who do not have contraindications. ACIP recommends the use of any licensed, recommended, age-appropriate vaccine, meaning a number of influenza vaccines are available for children, older adults, and those with allergies. Maintaining adequate vaccination uptake ensures that populations who may be at particular risk for severe infection or who may be unable to receive the influenza vaccine are still protected from disease because others have been vaccinated.
• Protection against disease severity: Recent analysis suggest that influenza vaccination has reduced the severity of illness and has prevented nearly 6.2 million illnesses and 100,000 annual deaths. A CDC-supported study found that vaccination reduced the risk of severe illness and hospitalization by 37% and reduced admission to the intensive care unit by 82%. Vaccinated adults were 59% less likely to have severe illness. While influenza vaccination will not reduce the severity of COVID-19 infection, keeping people out of physician offices and hospitals may in turn simplify COVID-19 detection.
• Timing of vaccination: Seasonal vaccination is currently the most effective way to maintain pandemic preparedness. While it is often believed that vaccination does not provide needed protection after October, the recommended time for vaccination, CDC acknowledges that vaccination as late as January, can still provide protection for the remainder of the season, reducing overall burden of disease and severity of illness.
• Vaccine safety: Healthy adults have, in certain cases, forgone vaccination out of fear that the influenza vaccine could lead to infection. While some people do report instance of mild reactions to influenza vaccines, as they do with other vaccines, influenza vaccines have not been shown to lead to active infections. There are a host of reasons why some may experience flu-like symptoms following vaccination, including exposure to other respiratory illness, including rhinovirus and the body’s natural response to being exposed to the virus as it builds a strengthen immune response.

Technologies Reshaping the Influenza Vaccine Landscape

In 2019, President Trump signed an executive order (EO) directing Health and Human Services to encourage increased and modernized influenza vaccine production, as well as reduced national reliance on egg-based influenza vaccines. To ensure pandemic preparedness, the EO called for the further development of alternative and more rapid production methods, although it has not announced any further action or targeted technology advancements stemming from the EO.

Nevertheless, new and emerging technologies are poised to reshape the influenza vaccine market landscape and increase vaccination rates. These technologies include:

• Universal influenza vaccines: This vaccine could be at least 75% effective against all Type A influenza viruses known to cause significant seasonal illness. Although these vaccines are in early development, they may protect against H1N1 strains, which were the cause of the most recent 2009 pandemic, increasing overall vaccine confidence.
• Non-egg-based vaccine production: In addition to existing cell-based and recombinant manufacturing technologies, as well as an egg-free vaccine, increased production of non-egg-based vaccines offers several advantages over traditional egg-based production. Start-up times for manufacturing are considerably shorter compared to traditional production, allowing for faster response in the event of another major outbreak like the 2009 H1N1 pandemic. Egg-free vaccines create a pathway for vaccination for those with allergies. Overall, moving away from egg-based vaccine production to cell-based and recombinant will reduce the reliance on consistent egg supply, which—if compromised—could lead to significant disruptions in vaccine production and supply.
• High-dose and adjuvanted vaccines: A high-dose vaccine, indicated for adults ages 65 and older, and the recently-approved quadrivalent adjuvanted vaccine are currently leading in the older adult market, having accounted for the highest market share for every influenza season since 2015. High-dose vaccines, which contain considerably larger amounts of antigen than other vaccines, and adjuvanted vaccines are intended to induce a stronger immune response and may offer increased protection for vulnerable populations.
• Non-injectable vaccines: Most recently, ACIP reestablished its recommendation for a non-injectable influenza vaccine administered via intranasal spray for the 2018–2019 season. A needle-free influenza vaccine may significantly increase uptake, bypassing hesitation resulting from fear of needle stick.
• Self-administered vaccines: Possibilities for self-administering influenza vaccines have also entered the pipeline and present another opportunity to reshape the market, increase access to influenza vaccines, and improve uptake. A heat-stable, potentially painless vaccine may increase willingness to be vaccinated and additionally improve access, particularly during major outbreaks. Reducing the need to visit a physician’s office or pharmacy to be vaccinated can increase the ease of vaccination, while also reducing risk of exposure to both influenza and other infectious diseases.

As COVID-19 disease burden continues to rise, it is important to recognize the consistent burden of diseases associated with influenza infection. Several novel emerging products could make vaccination more accessible and effective, potentially reshaping the market and lowering influenza disease burden.

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