BNT162b2 COVID vaccine humoral response substantially reduced after 6 months

The rollout of vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is expanding worldwide. However, little is known about the duration of protection offered by these vaccines. Real-world data on the kinetics of antibodies are beginning to appear, but a holistic picture of immunity duration is still not available.


Extensive randomized controlled trials and real-world studies have been conducted, which have revealed the efficacy of the BNT162b2 vaccine to be 94 to 95% in preventing symptomatic coronavirus disease 2019 (Covid-19), after seven days of receiving the second vaccine dose. The antibody levels in certain groups have been seen to be lower and these include the elderly, men, and immunosuppressed individuals. This observation suggests that the antibody titers could be declining faster in these groups.

Researchers monitored 197 vaccinated individuals and noted that anti-spike (S) antibody levels peaked at 21 to 40 days post-administration of the second dose of the vaccine. The anti-spike (S) antibody levels declined by a factor of two by the 84th day. A new research paper has been published in the New England Journal of Medicine that reports on a large-scale study involving health care workers in Israel to assess the kinetics of immune response over six months post-administration of the second dose of the BNT162b2 vaccine.

A New Study

The time period of the study was from December 19, 2020, to July 9, 2021. A total of 4,868 health care workers were recruited. The participants provided blood samples for serologic assays before receiving the first vaccine dose. Subsequently, blood samples were provided monthly for 6 months after receipt of the second dose. Only adults with no prior history of SARS-CoV-2 infection were included in the study. If participants had breakthrough infections, they were removed from the study. Antibodies were tested in the baseline period (4-17 days after receiving the second dose) and monthly thereafter. For this study, researchers selected a subgroup that included vulnerable individuals, such as individuals above 65 years of age and persons with pre-existing conditions.

Main Findings

The highest antibody titers were observed during days 4 through 30 (after receiving the second dose), which was defined as the peak period. Subsequently, a substantial reduction in Immunoglobulin G (IgG) levels was observed each month. The IgG levels had declined by a factor of 18.3 over the six-month study horizon. A similar pattern was observed for neutralizing antibodies, which decreased by a factor of 3.9 initially. The decline was much slower in the later months of the study horizon, i.e., by a factor of 1.2. The antibody titer decline was associated with age, sex, and pre-existing conditions. Older men and immunosuppressed individuals were identified to be the most vulnerable.

Neutralizing antibodies correlate with protection; however, neutralizing assays are time-consuming and complex. In this study, scientists found a strong correlation between anti-S IgG and neutralizing antibody levels, but this relationship was dependent on time. They also observed that antibody levels were higher in women and decreased with age. Significantly lower antibody response was found among immunosuppressed persons, whose neutralizing antibody titers were lower by a factor of 5, compared with healthier participants.

Researchers observed that obese individuals had a significantly higher neutralizing antibody titer during long-term follow-up. The previous research has shown that obesity correlates with severe COVID-19. Future research will need to investigate whether vaccinated obese persons are at higher risk of breakthrough infection and the kinetics of antibodies in obese individuals.

Scientists have also highlighted the superior durability of humoral response in persons recovered from SARS-CoV-2 infection. Such individuals showed a modest decline in IgG and neutralizing antibody levels at 8 to 10 months after the infection. This could be the reason for the significantly lower number of breakthrough infections among previously infected individuals compared to vaccinated persons. Overall, existing evidence indicates that long-term humoral response and vaccine effectiveness are higher in individuals previously infected by SARS-CoV-2 than vaccine recipients.


One limitation of the current study could be the under-representativeness of the population. The health care workers who participated in the study were primarily healthy individuals. To this end, however, scientists considered a sub-group comprising older persons or persons with coexisting conditions. The times ahead are still quite uncertain and as the pandemic continues to evolve, it will be important to determine the immune correlates of protection after vaccination. The data provided in the current study provides important insights into the kinetics of the immune response to BNT162b2 vaccination. More research is needed to develop new strategies to prolong host immunity to protect the global population against SARS-CoV-2 and its variants.

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Gemma Wilson

Gemma is a journalism graduate with keen interest in covering business news – specifically startups. She has as a keen eye for technologies and has predicted quite a few successful startups over the last couple of years.

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