Humoral and cell-mediated immunity six months after BNT162b2 vaccination

A recent study by health professionals in Japan has evaluated vaccine-induced humoral and cellular immunity to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) six months after BNT162b2 (Pfizer-BioNTech, USA) vaccination.

Study: Vaccine-induced humoral and cellular immunity to SARS-CoV-2 6 months after BNT162b2 vaccination.  Image credit: cortex film / ShutterstockStudy: Vaccine-induced humoral and cellular immunity to SARS-CoV-2 6 months after BNT162b2 vaccination. Image credit: cortex film / Shutterstock

The research team observed a sharp decrease in IgG antibodies specific for nail protein (SP) six months after vaccination compared to the levels three weeks after the second vaccine dose. However, the decrease in the humoral index is weakly correlated with the observed cellular immune response.

A pre-printed version of the research paper is available at medRxiv* server while the article is undergoing peer review.


Vaccination has provided a strong strategy to control the pandemic with coronavirus disease-2019 (COVID-19). Pfizer-BioNTech’s BNT162b2 vaccine became the first to receive emergency validation from the World Health Organization (WHO) for use against SARS-CoV-2.

Phase 3 trials with most vaccines showed high efficacy. However, reports pointing to the long-term decline in vaccine efficacy and the prevalence of breakthrough infections have created a major concern across the globe. It is said that most vaccines have a declining effect six months after vaccination. However, it is reported that the potency of a vaccine to prevent serious illness persists at high levels.

The decrease in vaccine efficacy can be attributed to the decrease in antibody titers or humoral immunity. However, cellular immunity may just as well play an even greater role in the prevention of severe COVID-19 than has hitherto been understood.

What did the researchers do?

The study was performed on 98 healthy healthcare professionals from Yokohama City University Hospital, Japan, who had taken two doses of the BNT162b2 vaccine from March to April 2021.

The team determined SP immunoglobulin (IgG) levels against SARS-CoV-2 using chemiluminescent enzyme immunoassay (CLEIA) six months after vaccination. Data on SP IgG index titers for early weeks from this study were also compared with the observations at six months.

Later, a 50% neutralizing titer (NT50) was calculated from the neutralizing titer assay using an HIV-based pseudovirus carrying the SARS-CoV-2 tip.

In addition, SARS-CoV-2-specific T cell response in the form of spot-forming cell counts (SFC) was evaluated by interferon (IFN) -γ ELISpot assay to assess the status of cellular immunity six months after vaccination.

What did the researchers find out?

Humorous immune index

The team observed a surprising decrease in antibody titers, with only 1/15 titers noted after six months compared to those at three weeks after the second dose of the BNT162b2 vaccine. The geometric mean titers (GMT) of SP-specific IgG decreased from 95.2 (95% confidence interval (CI); 79.8-113.4) three weeks after vaccination to only 5.7 (95% CI; 4.9 -6.7) after six months.

A similar trend was noted for NT50, which also showed a marked decrease in GMT from 680.4 (95% CI; 588.0–787.2) after three weeks to 130.4 (95% CI; 104.2–163 , 1) after 6 months.

There were four patients with a history of breakthrough infections that occurred after completing the second dose of vaccine. In these, SP IgG index titers ranged from 146.1 to 459.1, while NT50 ranged from 1631 to 8756 after six months. High antibody titers observed in these patients are thought to be induced by the breakthrough infection cases.

The team observed a negative association between the SP IgG index titer and alcohol consumption. GMT for SP IgG index titers among non-drinkers was significantly higher than among current drinkers {7.57 (95% CI 5.89, 9.73) vs. 5.34 (95% CI 3.37, 8.44)}. In addition, multivariate regression analysis revealed that age was another factor that was negatively correlated with the SP IgG index titer.

Cellular immune index

The correlation between cellular immunity, assessed by the SP-specific T cell response, and humoral immunity, measured by SP IgG index titer, was weak, indicating a different dynamic for a cellular immune response from the humoral.

A previous study had reported 184 SFC / 106 peripheral blood mononuclear cells (PBMCs), a measure of SP-specific T cell response, immediately after BNT162b2 vaccination. The SP-specific T cell response observed in this study was 84 SFC / 106 PBMCs six months after vaccination. The decrease in cellular immunity was slower than the antibody titer, indicating that it is less negatively correlated with age, possibly explaining its long-term effect in protecting against developing the severe form of this disease.

*Important message

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


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