Why are (COVID) Vaccines Not Perfectly Effective?

And what does this mean for the pandemic?

Prefer to listen to this story? Tune in here.

Medical science has always been imperfect. Stories of individuals’ cancer relapsing, not everyone treated for a heart attack making it, and antibiotics not enough for bacterial infections are all too familiar. Before COVID-19, it was not uncommon to hear of someone who got the flu shot and still developed the illness.

There are ready answers to why medical science was imperfect in the past and why it remains imperfect with COVID-19 vaccines (and most other things). Ultimately, it rests in finding treatments that meet the combined diversity of individuals, diseases, and infectious organisms. COVID-19 vaccines must navigate all these systems, which is hard even for conditions we have had more time to think about, such as influenza.

The interaction of systems inherent to our biology, such as genetics, with what we are exposed to in the environment forms the basis of a living system. Such interactions drive disease, including infectious disease, and make it hard to model and create predictions. Complex genetic traits can influence one’s chance of developing lung cancer. Smoking for a few decades can contribute to this risk while being enough in some cases to develop the condition. While this is a fairly basic example, many other interactions can contribute, many remain poorly understood.

As we know, there are multiple types of this virus that causes COVID-19. The current convention in the literature is to differentiate these variants by their nuances in a small part of the viral genome, specifically in the spike protein. These interactions are relevant to COVID-19 with the additional interaction of another organism, SARS-CoV-2. For purposes of the vaccine, which relies on stimulating an immune response against this protein, this level of understanding is enough because it forms a key component of what is required for SARS-CoV-2 to cause infection.

When vaccines are made for infectious diseases, whether for COVID-19 or influenza, the objective is to create a treatment that can offer protection against all (or almost all) the known variability in a virus. What makes this challenging is that viruses change, as we have seen. The subunits that make up the spike protein have changed to different subunits.

Some of these changes have made the virus more infectious, which means that the specific variant is more likely to become common. When we think of all the spike protein subunits of everyone infected with COVID-19 and people at risk of developing the infection, we can imagine how the more infectious subunits could ultimately dominate. This is what has happened with the Delta and Omicron variants.

While computer modelling is pretty good in predicting how these subunits will change over time, it is not perfect. It is impossible to know the future. All we can do is predict. Predictions inherently come with a risk of imperfection. Think of the last weather forecast you read. Fortunately, estimates of how the virus would change have been pretty good, and vaccines still afford a lot of protection against SARS-CoV-2, including the Omicron variant. It is also clear how a changing landscape could pose challenges for future vaccine effectiveness.

SARS-CoV-2 is changing. Vaccine developers knew this would happen and did a great job producing a therapy that would afford protection despite this. One can understand how making predictions is challenging, especially when considering how rapidly the virus can change when many people get infected. Fortunately, vaccine makers have already started clinical trials for vaccines more suited to the current and future climate of SARS-CoV-2. While we may need additional shots in the future, we can rest assured that they will afford the protection required for the time. They may not be perfect, but as we have seen, imperfect is still pretty good and largely prevents the fundamental issue of severe disease.


Medika Life has provided this material for your information. It is not intended to substitute for the medical expertise and advice of your health care provider(s). We encourage you to discuss any decisions about treatment or care with your health care provider. The mention of any product, service, or therapy is not an endorsement by Medika Life

Julian Willett, MD
Julian Willett, MD

M.D. trained in the US, now researching SARS-CoV-2 and COVID-19 in Canada for his Ph.D. After earning my Ph.D., I will be pursuing an Anatomic Pathology residency embracing my path towards being a physician-scientist. My academic interests are directed towards topics that provide the greatest net benefit for the greatest number of people. I love complicated, messy, and poorly understood topics.

I enjoy writing in my spare time, along with 3D printing and staying connected with my family. I have been a longstanding proponent for global health with projects ranging from supporting Doctors without Borders (MSF) to Syrian refugees (Syrian American Medical Society). 

More from this author