Evaluation of immunogenicity after BNT162b2 booster vaccination

In a recent study published on Research Square* preprint server, researchers assessed levels of immunoglobulin (Ig) G and IgA antibodies in serum samples from healthcare workers (HCWs) before vaccination, after the first dose of vaccine, after eight months of the first dose and after receiving the booster.

Study: Evaluation of immunogenicity after BNT162b2 booster vaccination in healthcare workers. Image Credit: Steve Heap/Shutterstock


It is crucial to assess the decline of the immune response in healthcare workers, a high-risk population that remains in constant contact with patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

The world has entered the third year of the coronavirus disease 2019 (COVID-19) pandemic, but there is no specific treatment for this deadly infection. Therefore, vaccinations and the development of herd immunity are the only effective ways to mitigate the adverse effects of COVID-19.

In this scenario, monitoring the characteristics of HCWs and their response to vaccination provides an opportunity to examine vaccine effectiveness (VE), extrapolate it to a larger population, and guide public health decisions.

About the study

In the current study, researchers recruited 103 healthcare workers vaccinated with the BNT162b2 vaccine in January 2021. Test subjects included mostly females with an average age of 40.26 years. They had several comorbidities, including obesity, allergies, diabetes, hypothyroidism and cardiovascular disease.

Researchers followed test subjects before and after vaccination between May 2020 and October 2021 to assess serum IgG and IgA levels at different time points – immediately after the primary vaccination, at the eight-month follow-up, before the third booster dose. , and up to three weeks after receiving the booster dose.

The team performed an enzyme immunoassay (ELISA) to determine serum anti-SARS-CoV-2 IgG and IgA levels.

Study results

All subjects tested had elevated IgG and IgA levels after receiving the first dose of the vaccine, regardless of their pre-vaccination infection status. Moreover, age, sex or pre-existing comorbidities did not modify the antibody response after vaccination. Therefore, further studies are warranted to determine the correlation of age and sex with the immune response induced by BNT162b2 vaccination.

Eight months after the first vaccination cycle (between January and October 2021), the average levels of IgG and IgA decreased by 2.4 times and 2.7 times respectively. After the boost, IgG and IgA levels immediately increased 2.7 and 2.5 times, respectively. IgG levels after the booster vaccination were statistically higher than those obtained by the first vaccination; however, IgA levels after the booster were comparable to those achieved after the first vaccination.

In a study conducted on healthcare workers in Germany, researchers observed that SARS-CoV-2-specific IgM and IgA antibodies declined rapidly over time, while IgG decreased slowly. Additionally, subjects previously infected with SARS-CoV-2 induced higher IgG levels and lower IgA levels after a booster vaccination. The study clarified that the correlation between total antibodies and their neutralizing ability is not yet fully understood.

On the other hand, studies have demonstrated that the booster dose improves both the quantity and the quality of anti-SARS-CoV-2 antibodies, inducing neutralizing titers significantly higher than the titers obtained after the vaccination series in two doses.

In one of the cases, where there were no detectable IgG and IgA antibodies after eight months after the first vaccination, the booster rapidly induced high levels of IgG and IgA antibodies during the first week. IgG and IgA levels continued to rise two to three weeks after receiving the booster. Interestingly, anti-S IgG antibodies exceeded previously achieved antibody levels after the first vaccination dose, suggesting robust cellular memory.

Regarding post-vaccination side effects, the booster shot caused mild pain at the injection site in more than 75% of the subjects tested.

Nine study group subjects (8.73%) developed COVID-19 four months after the boost, demonstrating that novel, genetically distinct SARS-CoV-2 variants have the potential to evade established immune memory.


Although knowledge regarding antibody and cell persistence is sparse, the study highlighted the complex regulatory mechanisms that regulate the generation of immune memory after natural infection and vaccination.

The third dose of the BNT162b2 vaccine (booster) addressed the issue of waning immunity and initially circumvented ineffectiveness against SARS-CoV-2 variants; however, after five months, immune protection elicited by the booster dose declined dramatically. Therefore, further clinical studies are needed to verify its safety, assess its necessity, and determine whether it is necessary to take an additional dose after the booster.

*Important Notice

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

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