In a recent study published on the medRxiv* preprint server, scientists evaluate the humoral and cellular immune responses in individuals who have received a third booster dose of messenger ribonucleic acid (mRNA)-based coronavirus disease 2019 (COVID-19) vaccine by Pfizer/BioNTech. The findings highlight that the booster dose induces a robust immune response, which is significantly higher than that induced by two vaccine doses alone.

Study: Cellular and humoral immune response to a third dose of BNT162b2 COVID-19 vaccine – a prospective observational study. Image Credit: Chaay_Tee / Shutterstock.com

Background

The beginning of COVID-19 mass vaccination campaigns at the end of 2020 led to an initial reduction in infection rates worldwide. However, due to the emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), variants, coupled with the gradual waning of vaccine efficacy, a resurgence of COVID-19 cases has been observed in many countries across the globe.

To improve vaccine efficacy and prevent breakthrough infections, many countries have begun administering the third booster of COVID-19 vaccines to susceptible individuals, including elderly people and front-line workers. Some countries have also selected a heterologous vaccination strategy to immunize at-risk populations. In this strategy, different types of vaccines targeting the same viral protein have been used to prime and boost antiviral immunity.

In the current study, the scientists evaluate the humoral and cellular immune responses induced by a third booster dose of Pfizer/BioNTech vaccine in individuals who have been primed with Pfizer/BioNTech vaccine (two doses), Oxford/AstraZeneca vaccine (two doses), or a combination of both vaccines.

About the study

The current study included 243 healthcare workers who received the third booster dose more than six months after the second vaccination. Among recipients of the booster dose, about 73% were primed with two doses of the Pfizer vaccine, 5% were primed with two doses of the adenovirus vector-based AstraZeneca vaccine, and 20% were primed with one dose each of Pfizer and AstraZeneca vaccines.  

Blood samples were collected from the participants before and four weeks after receiving the booster dose. All participants were also asked to complete a questionnaire that was designed to gather information on demographic characteristics, prior vaccination status, smoking status, and vaccine-related side effects.

The humoral response was evaluated by measuring the blood levels of binding and neutralizing antibodies targeting the SARS-CoV-2 spike protein. In addition, the cellular immune response was evaluated by measuring the interferon-gamma (IFN-γ) levels.  

Vaccine-induced immune responses in the entire study population

All participants showed detectable levels of anti-SARS-CoV-2 antibodies at baseline before receiving a third booster dose.

The average level of anti-SARS-CoV-2 binding antibodies increased significantly in all participants after booster vaccination as compared to that after the second vaccination. A similar induction was also noticed for anti-SARS-CoV-2 neutralizing antibodies.

About 73% of participants showed detectable T-cell levels at baseline before receiving a third booster dose. The frequency of participants with detectable T-cell responses increased to 96% after receiving a booster dose. A significant induction in IFN-γ levels was also observed after booster vaccination.

Vaccine-induced immune responses in specific study groups

Before booster vaccination, the highest levels of anti-SARS-CoV-2 binding antibodies were observed in individuals primed with two doses of AstraZeneca vaccine, followed by heterologous vaccine-primed individuals. The administration of a booster vaccine led to a significant induction in binding antibody levels in all subgroups analyzed.    

After receiving the booster vaccine dose, a significant induction in neutralizing antibody levels was observed in all three subgroups. Individuals primed with the Pfizer vaccine exhibited the lowest level of IFN-γ, followed by Pfizer/AstraZeneca vaccine-primed, and AstraZeneca vaccine-primed individuals.

A significant induction in T-cell responses was observed in all subgroups following booster vaccination. This induction was highest in individuals primed with Pfizer and AstraZeneca vaccines, followed by Pfizer vaccine-primed and AstraZeneca vaccine-primed individuals.

Factors influencing immune responses

The scientists conducted statistical analyses to identify factors that may influence antibody levels following booster vaccination. To this end, body mass index (BMI) and pre-booster antibody levels were found to be two strong predictors of booster-induced induction in antibody levels; however, no significant effect of age, sex, smoking status, and prior infection on post-booster antibody level was observed.

Regarding side effects of booster vaccination, most of the participants reported minor side effects, with about 22% reporting no local or systemic adversities.

Conclusions

The current study highlights the importance of COVID-19 booster vaccines in inducing robust humoral and cellular immune responses in individuals primed with homologous or heterologous vaccines. Importantly, the study reveals that pre-booster antibody levels and BMIs strongly predict the robustness of post-booster antibody responses.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Dr. Sanchari Sinha Dutta

Dr. Sanchari Sinha Dutta is a science communicator who believes in spreading the power of science in every corner of the world. She has a Bachelor of Science (B.Sc.) degree and a Master's of Science (M.Sc.) in biology and human physiology. Following her Master's degree, Sanchari went on to study a Ph.D. in human physiology. She has authored more than 10 original research articles, all of which have been published in world renowned international journals.