Long-term humoral response and its determinants after 2- and 3-dose COVID-19 mRNA vaccines

In a recently published study medRxiv* Preprint servers, the researchers compared the lapses in vaccine-induced immunity after two and three doses of the messenger ribonucleic acid (mRNA) coronavirus disease 2019 (COVID-19) Pfizer-BioNTech vaccine BNT162b2 by performing a repeat serological study to evaluate the prolonged perform humoral response.

Study: Durability and determinants of anti-SARS-CoV-2 spike antibodies after second and third doses of mRNA-COVID-19 vaccine. Image source: Christoph Burgstedt/Shutterstock


The concerted global effort to develop vaccines and to administer a two-dose primary vaccination schedule to large segments of the world population has resulted in limiting morbidity and mortality associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. guided.

Various studies have evaluated the long-term effectiveness and wear-off of the first two doses in different age groups, consisting of the elderly, women and people with previous SARS-CoV-2 infections. The results of these studies have been instrumental in formulating public health policy regarding booster vaccinations.

However, waning of antibody responses due to comorbidities such as obesity, immunosuppression, and other serious diseases has not been studied for the primary immunization regimen or the third booster dose. Understanding the factors that determine long-term humoral immunity is critical to formulating public health decisions during the ongoing COVID-19 pandemic.

About the study

In the present study, researchers conducted six serological surveys among staff at the National Center for Global Health and Medicine (NCGM) in Japan between July 2020 and June 2022. At NCGM, the in-house vaccination provided to employees consists of two doses of the Pfizer-BioNTech BNT162b2 mRNA vaccine between March and June 2021 and a booster dose between December 2021 and February 2022.

The survey measured antibodies against the SARS-CoV-2 nucleocapsid and spike proteins and collected patient information with data on COVID-19 vaccination status, previous SARS-CoV-2 infections, comorbidities, body composition and behavioral factors. Vaccination status and self-reported prior SARS-CoV-2 infection were confirmed from NCGM records.

Of the data collected, some were excluded due to lack of information on body mass index, immunosuppressive treatments, underlying health conditions, smoking or alcohol consumption behavior and discrepancy between SARS-CoV-2 infection reports and seropositive anti-SARS-CoV-2 nucleocapsid protein -Assays.

Information on demographic factors, body mass index, illness, history of immunosuppressive therapy, and tobacco and alcohol use were collected from a questionnaire survey after obtaining informed consent. The comorbidities recorded in the questionnaire included cardiovascular disease, renal disease, hypertension, cancer, dyslipidemia and diabetes. The survey also asked for information about cancer treatments, non-topical and non-inhaled steroids, and immunosuppressants. Drinking alcohol once a week was considered regular alcohol consumption.

Statistical analyzes were performed to find correlations between decreasing antibody titers and demographic, comorbidity, and lifestyle-related determinants.


The results showed an overall decrease in antibody decline rates after the booster dose. In addition, antibody decline rates in individuals with hybrid immunity have been further reduced by vaccination and previous SARS-CoV-2 infections. Individuals with three vaccine doses and a prior SARS-CoV-2 infection had a 21% decrease in antibodies per 30 days compared to individuals with two vaccine doses and a prior SARS-CoV-2 infection who had a rate of decrease every 30 days 16% had days.

Determinant variables such as advancing age, obesity, comorbidities, smoking, alcohol consumption, immunosuppressive therapy, and male gender were associated with decreasing antibody titers after the second dose. These correlations disappeared for antibody titers after the booster dose, except for immunosuppressive therapy and female sex.

While the results suggest that hybrid immunity resulted in a lower rate of decline in antibodies than vaccination-induced immunity alone, an interesting pattern was observed where two doses and previous SARS-CoV-2 infection resulted in more durable antibodies than three doses and a previous infection. This suggested that SARS-CoV-2 infection produced more durable antibodies than vaccination.

Furthermore, there were no differences in the durability of antibody titers based on the sequence of infections and vaccinations or the dominant variant circulating during infection, suggesting that the durability of antibody titers was not different from that for SARS-CoV-2 infection responsible variant was influenced.

The decline in antibody titers in subjects undergoing immunosuppressive therapy, regardless of the number of vaccine doses, suggested the need for ongoing infection monitoring and increased booster vaccinations for these subjects.


Overall, the results showed that antibody titers were more durable and long-lasting in people who received booster shots and had previous SARS-CoV-2 infections, regardless of the infectious variant.

While primary vaccinations were associated with decreasing antibody titers in elderly, comorbid, obese, male, or immunosuppressive therapy groups, these associations were no longer evident after the third dose of vaccination, except in women and those on immunosuppressive therapy. The results underscore the need to monitor infections and give booster doses to patients undergoing immunosuppressive therapy.

*Important NOTE

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

Leave a Comment