Does a COVID-19 vaccine booster improve the immune response of a poor responder?

Scientists have reported that the immune response elicited via coronavirus disease 2019 (COVID-19) vaccination or natural infection wanes off over time. The rapid outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) resulted in the COVID-19 pandemic that has claimed more than 5.27 million lives worldwide.

Study: Third COVID-19 Vaccine Dose Boosts Neutralising Antibodies in Poor Responders. Image Credit: davide bonaldo/ShutterstockStudy: Third COVID-19 Vaccine Dose Boosts Neutralising Antibodies in Poor Responders. Image Credit: davide bonaldo/Shutterstock

To date, all the available COVID-19 vaccines and therapeutics have been designed to target the spike protein of SARS-CoV-2. Particularly, antibodies generated after natural infection or COVID-19 vaccination neutralize the virus by binding to the receptor-binding domain (RBD). Therefore, neutralizing antibodies (NAbs) inhibit the spike protein of SARS-CoV-2 from binding to the angiotensin-converting enzyme 2 (ACE2) receptor of the host cell receptor and, thereby, protecting an individual from the infection.


Several COVID-19 vaccines have received emergency use authorization (EUA). Scientists have stated that these vaccines protect individuals from severe illness and help reduce the mortality rate. Many reports of breakthrough infection have been reported, and some studies have indicated that 5% of vaccinated individuals remain susceptible to infection and acute disease.

Typically, antibodies specific to SARS-CoV-2 are generated via natural infection or COVID-19 vaccination, protecting an individual from infection. Another type of immune protection is the production of T-cells which protects a person from a viral infection; however, its activity is difficult to gauge at scale.

Previous studies have shown that two doses of BNT162b2 or mRNA1273 COVID-19 vaccine produce antibodies against the spike protein, and these studies also determined the durability of these antibodies. The levels of nAb in an individual are mostly correlated with the degree of protection one possesses against the infection. Some studies have indicated that antibodies are not produced in everyone administered with the vaccine, and these individuals/groups are referred to as poor responders to the SARS-CoV-2 vaccine.

A new study

A new study, published on the medRxiv* preprint server, has focussed on determining the levels of nAb in individuals who received the second and third doses of the RNA vaccines developed by Pfizer and Moderna. In this study, researchers collected blood samples from participants at a particular time interval, i.e., 2-4 weeks and 2-4 months after their second RNA vaccination. They also collected samples during pre and post third RNA vaccine doses.

The authors quantified the NAb levels, using a semi-quantitative rapid test, among 269 healthy individuals whose ages ranged from 19 to 80 years. The study cohort included 165 female and 104 male participants.

Twenty-three of the participants received either three doses of BNT162b2 or the mRNA-1273 vaccine. Some participants received two doses of BNT162b2 followed by a third dose of mRNA-1273. In this study, researchers aimed to determine the levels of antibodies after the third dose of the COVID-19 vaccine.

Main findings

After the second dose of the vaccine, i.e., 2-4 weeks post-vaccination, researchers found that the neutralization ranged between 0% and 99% in the study cohort. They found that 57% of vaccine recipients demonstrated nAb levels above 75%. Interestingly, scientists observed that 25% of the study cohort did not show neutralization above 50% (<1:80) within a month of their second dose of RNA vaccine. However, the possibility of COVID-19 infection for this group or vaccine-poor responders (VPRs) is not yet determined. Although the average age of VPRs was 57 years, the age ranged between 19-80 years, and the average age of non-VPRs was 50 years.

This study has reported that twenty-three VPRs whose ages ranged from 31 to 79 years obtained a third dose of either RNA vaccine between 1-8 months after their second dose. Most importantly, this group showed an average 20-fold increase in nAb levels, i.e., 46%-99%. This finding holds extreme importance as previous studies have strongly suggested waning nAb levels with time after vaccination. The results of this study strongly indicate the effectiveness of the booster vaccination strategy. The third dose would ensure high nAb levels that would prevent infection, asymptomatic viral replication, and potential transmission.

Another important factor indicated by this study is that individuals must evaluate their nAb levels via inexpensive, rapid tests. This would distinguish individuals who should receive a booster vaccine from those who do not. Researchers believe VPRs could be a source of breakthrough infections.


The authors mentioned some of the limitations of this study, which include that it is still unclear what levels of neutralizing antibodies protect against infection. Previous studies have reported that the N-terminal domain of spike protein has also been shown to neutralize SARS-CoV-2; however, this study did not determine its level as it is considered a minor component of neutralizing antibodies.

The current study has shown the importance of booster dose strategy, especially for those who responded poorly to two doses of COVID-19 vaccines. At present, longitudinal studies are being conducted to determine if high levels of nAb in recipients of a third vaccine dose are more sustainable than nAb levels after two doses of RNA vaccines.

*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.

Journal references:
Dr. Priyom Bose

Written by

Dr. Priyom Bose

Priyom holds a Ph.D. in Plant Biology and Biotechnology from the University of Madras, India. She is an active researcher and an experienced science writer. Priyom has also co-authored several original research articles that have been published in reputed peer-reviewed journals. She is also an avid reader and an amateur photographer.


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The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
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