Vaccine Booster Shots

Vaccines trigger the production of disease-specific antibodies that ensure our bodies are prepped for subsequent exposure. However, this immunity does not necessarily last forever. Often, the body's level of immunity, whether it is triggered by exposure to a pathogen, either via direct infection or through vaccination, wanes over time. For virus-borne diseases, the evolution of new viral variants also presents our immune system with a novel challenge to overcome, as we are witnessing right now with the emergence of new and more transmissible variants of SARS-CoV-2. These are two scenarios that typically warrant the administration of vaccine boosters, providing the immune system with a renewed push in its preparedness to fight the infection.

What is a booster, and why are they needed?

Over time, antibodies produced by a vaccine degrade and when their levels fall below a critical threshold, they may not provide the intended protection. Vaccine boosters are additional doses of a vaccine that, as the name suggests, boost the protective effect of the vaccines. By triggering the immune system to generate the same response as if it were under attack by invading bacteria or viruses, the booster dose further strengthens the immunity provided by the vaccine. However, to boost or not to boost often depends on the individual as well as the particular vaccine.

To boost, or not to boost?

Professor Calman MacLennan, a vaccine immunologist at the University of Oxford, who leads BactiVac, a global bacterial vaccinology network and works for the Bill & Melinda Gates Foundation, explained why and when we need vaccine boosters: "Once you introduce a vaccine, there are longitudinal studies that follow what happens with people who are vaccinated."

Assessment of the necessity of boosters requires continuous monitoring of the vaccinated population over a long time. MacLennan explained, “The duration of protection is an important component of understanding how the vaccine works. If you start to see breakthrough cases of a disease that you were vaccinated against after a period of time, that's when the question about boosting will come in.”

Antibody decay occurs at different rates for immunity that is gained by an infection as opposed to that by vaccination, and also varies between individuals. Young children, the elderly and immunocompromised patients are generally most at risk of reinfection. This is why common vaccines for children, such as the DPT vaccine that protects against diphtheria, pertussis, tetanus or the polio vaccine, require multiple booster shots.

Vaccines and vaccine boosters also exist for endemic infectious diseases. These are diseases that persist in a particular population and frequently lead to local outbreaks. For some endemic diseases, you may not require vaccines in your home country, but they may be necessary for traveling abroad. For example, many African countries require proof of yellow fever vaccination for all incoming travelers. Poor access to vaccination and high density of mosquitoes, vectors for the virus that cause the disease, ensures that the virus perseveres in the local populations. In 2013, the WHO Strategic Advisory Group of Experts in Immunization concluded that a single dose provided sufficient immunity for most people, eliminating the need for boosters. However, recent evidence suggests that travelers spending a long time in areas that have seen recent outbreaks during peak transmission season would be better off with booster doses.

The how and when of designing vaccine boosters

Vaccine boosters are often an additional dose of a vaccine that was previously administered. In this case, their manufacture does not involve any special considerations beyond the initial vaccine manufacture. However, some vaccines may need an update in the design process, as is the case with annual flu shots.

“In some cases, we actually have a change in the vaccine. The annual influenza vaccine is changed every year, based on what is predicted to be the most prevalent circulating strains of influenza for the coming flu season,” said MacLennan. He stressed, however, that he doesn't call them "booster" shots in the strictest definition of the term and that they are reformulations of existing vaccines.

For these vaccines, the underlying technology remains the same with slight modifications that enable them to better target new strains or variants. The focus here, MacLennan emphasized, is "changing the antigenic composition or the antigens of the pathogen, in this case, influenza, which are essentially the proteins contained within the influenza virus".

Different strains emerge via two processes — antigenic drift and antigenic shift. In the former, there is a rapid accumulation of small mutations in the viral genome due to high immune selection pressure. This changes the structure of the surface proteins, hemagglutinin in the case of influenza, that the vaccines target. The latter, as its name suggests, is a more drastic change in the virus population and is a rarer event. In this case, two or more strains hybridize to form new subtypes that have antigens of the parent strains on the cell surface.

For most other vaccines, and for most people, boosters are not required annually, excluding the children, immunocompromised patients, and the elderly. Understanding when boosters are needed requires tracking how the protection from a vaccine fares over time for particular diseases. “If you understand what correlates with protection, then you don't have to look much for the disease,” MacLennan explained. “You can actually follow up [on] people who've been vaccinated, take repeat blood samples, so you can then see what's happened to their immunity. Now that's beneficial because it's much easier to take a blood test and measure someone's immunity than it is to wait for them to see if they get a disease or not because those disease events can be quite rare.”

Even though waning immunity in individuals is a metric that indicates a need for boosters, it’s not sufficient evidence on its own. Researchers need to correlate these measurements with a significant increase in cases. As MacLennan described, “At the end of the day, you're not vaccinating people to make sure that they have a particular immune response but to protect them against diseases."

Do we need COVID vaccine boosters?

Recently, the US government announced that it plans to administer COVID-19 booster shots. This sparked a debate among epidemiologists, vaccine researchers and public health experts about the need for this move, especially when there are billions of unvaccinated people globally, including tens of millions in the US. Currently, less than two percent of people in low-income countries have received a single dose.

Those in support of the US government's announcement suggest that booster shots are necessary to tackle the spread of the Delta variant. Dr. Jennifer Balkus, an infectious disease epidemiologist at the University of Washington, thinks otherwise. She and many other researchers are not convinced that the general population needs COVID-19 boosters right now. The ongoing debate is an excellent example of the kind of real-time questions experts ask about the need for vaccine boosters while tackling a pandemic.

“The US government’s recommendations for general population boosters are really based on data, some of which are not fully clear about possible reductions in efficacy against transmission and mild to moderate infection,” Dr. Balkus said. For instance, even though a recent report by the Center for Disease Control showed that 25% of the new cases in Los Angeles between May and July were among fully vaccinated people, the unvaccinated people were still nearly 5 times as likely to be infected and 29 times as likely to require hospitalization.

Dr. Balkus emphasized that “new variants are emerging through mutation, at least so far, in areas with limited vaccination". To address this situation, the priority continues to be vaccine distribution. She further argued that COVID-19 boosters for the general population are unethical as they essentially take resources away from the unprotected population. So, what kind of data in the future would be needed to convince Dr. Balkus of a need for vaccine boosters for the general population? “If we continue to see climbing rates of hospitalization and severe disease for individuals that have been vaccinated and the frequency of that becoming more similar to that we see among the unvaccinated," she said there would be cause for concern. That is a scenario that would "really indicate that vaccination is not having the ultimate protective effect", she added.

Conclusions and challenges

For researchers monitoring the COVID-19 pandemic, the question of whether boosters are reasonable will continue to be debated for the foreseeable future. Some suggest that all of us may require annual boosters for COVID-19, but others suggest that may be the case only for the most vulnerable.

For researchers working on influenza vaccines, the holy grail seems to be a universal flu vaccine – one that is applicable for preventing all strains. Such a vaccine would eliminate the need for the development of annual boosters, as well as minimize the possibility of influenza epidemics that break out when there is a mismatch between the antigen used in a vaccine and the antigen presented by the most prevalent strain.

Analyzing the necessity of booster vaccines for different diseases continues to be a challenge. In many developing countries, as well as poorer regions of developed countries, public health resources are generally stretched thin. Spending efforts on unnecessary vaccination diverts money and other resources from expanding the reach of first immunization. On the other hand, not giving boosters when there is a need carries the great risk of re-emergence or outbreaks of vaccine-preventable diseases. For example, the re-emergence of measles – a vaccine-preventable disease for which boosters are not recommended – is increasingly a cause of concern.

It is a complex situation that requires the continued, combined efforts of vaccine researchers, immunologists, epidemiologists and public health researchers.

About the author

Sachin Rawat is a freelance science and tech writer, currently working on data-driven content covering start-ups and technologies at StartUs Insights.