Improving Flu Vaccine Effectiveness Through Clinical Research and Adjuvants

The flu is one of the most common infections people regularly encounter. Every year there are about a billion cases of the flu worldwide, causing millions of hospitalizations and hundreds of thousands of deaths. The flu is caused by the influenza virus. It’s seasonal, and really kicks up in winter in temperate climates (like in most of the U.S.). To fight the flu, we engage in a huge public health initiative every year: the flu shot. The flu shot prevents millions of illnesses and doctor’s visits, tens of thousands of hospitalizations, and thousands of deaths each year.^[1] These excellent outcomes are in spite of the limited effectiveness of the flu vaccines.^[2] In this context, “effectiveness” measures how much disease a vaccine prevents compared to those who aren’t vaccinated. Large-scale studies have found that the flu vaccine can reduce hospitalizations by about 70% in adults.^[3] Adults over 65 may have weaker immune systems, so this effectiveness drops to between 42-60%.^[2,3,4] Flu vaccines, like the annual flu shot, are safe and effective, reducing the risk of illness and severe complications. While they are far better than treating people after they become sick, there remains room for improvement in vaccine coverage and overall effectiveness of the vaccines.^[5]

Vaccines are pretty simple in principle, but complex in practice. The general idea is to present a potentially dangerous particle to the immune system so it can recognize it and prepare defenses. The challenging part is the safety and effectiveness of this process in an unpredictable human body. Critical to effective vaccines are many steps, including introducing the correct “potentially dangerous” item (called an antigen), making sure the antigen isn’t actually dangerous, and - critically - ensuring the immune system actually responds.

This last part is where adjuvants come in. An adjuvant, from the Latin word for “to help,” is added to a vaccine to help increase its effectiveness. The exact mechanism for some adjuvants remains unknown, but scientists think they work through one of a few proposed methods:^[5,6]

• Helping move antigens to the lymph nodes for a long-term adaptive immune response

• Protecting antigens for a longer-term, bigger response

• Increasing the perceived threat during injection to bring immune cells to the antigens

• Stimulating an increase in total immune cells through danger signaling

• Activating secondary immune systems for a robust response

• Helping the immune system detect similar threats (such as a similar strain of influenza) even if they aren’t exactly the same

Some of the most widely used adjuvants, including alum (used for over 100 years) and MF59 (used for over 30), trigger local inflammation at the injection site.^[5] This inflammation causes a nonspecific immune response that enhances the overall effectiveness of the vaccine.^[5] While there is some concern about these adjuvants for potential chronic inflammation, more than a century of evidence shows that these potential risks are far outweighed by the benefits - namely, avoiding hospitalization or death from the flu or other diseases.^[5] Think of it like a tornado siren: it can be loud and unpleasant, but that’s a pretty good trade-off compared to getting hit with a tornado.

Flu vaccines are generally safe and provide important protection against influenza, but they could be more effective, especially for those over 65, who are at higher risk for severe illness. With the help of clinical trials, adjuvants may help make one of the most successful public health efforts even more effective for our most vulnerable populations.

Creative Director Benton Lowey-Ball, BS, BFA

References:

[1] Grohskopf, L. A. (2019). Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices—United States, 2019–20 influenza season. MMWR. Recommendations and Reports, 68. https://www.cdc.gov/mmwr/volumes/73/rr/rr7305a1.htm

[2] Gross, P. A., Hermogenes, A. W., Sacks, H. S., Lau, J., & Levandowski, R. A. (1995). The efficacy of influenza vaccine in elderly persons: a meta-analysis and review of the literature. Annals of Internal medicine, 123(7), 518-527. https://www.ncbi.nlm.nih.gov/books/NBK66348/

[3] Puig-Barbera, J., Diez-Domingo, J., Arnedo-Pena, A., Ruiz-Garcia, M., Perez-Vilar, S., Mico-Esparza, J. L., ... & Schwarz-Chavarri, H. (2012). Effectiveness of the 2010–2011 seasonal influenza vaccine in preventing confirmed influenza hospitalizations in adults: A case–case comparison, case-control study. Vaccine, 30(39), 5714-5720. https://www.sciencedirect.com/science/article/pii/S0264410X12010079

[4] Kwong, J. C., Campitelli, M. A., Gubbay, J. B., Peci, A., Winter, A. L., Olsha, R., ... & Crowcroft, N. S. (2013). Vaccine effectiveness against laboratory-confirmed influenza hospitalizations among elderly adults during the 2010–2011 season. Clinical infectious diseases, 57(6), 820-827. https://academic.oup.com/cid/article/57/6/820/330306

[5] Wilson, K. L., Xiang, S. D., & Plebanski, M. (2017). Inflammatory/noninflammatory adjuvants and nanotechnology—The secret to vaccine design. In Micro and nanotechnology in vaccine development (pp. 99-125). William Andrew Publishing. https://www.sciencedirect.com/science/article/pii/B9780323399814000063

[6] Schijns, V. E. (2000). Immunological concepts of vaccine adjuvant activity: Commentary. Current opinion in immunology, 12(4), 456-463. https://doi.org/10.1016/S0952-7915(00)00120-5