Humoral and cell-mediated immunity six months post BNT162b2 vaccination

A recent study of health care workers in Japan evaluated vaccine-induced humoral and cellular immunity against SARS-CoV-2 (SARS-CoV-2) six months after BNT162b2 vaccination (Pfizer-BioNTech, USA).

Study: Vaccine-induced humoral and cellular immunity against SARS-CoV-2 at 6 months after BNT162b2 vaccination. Image Credit: cortex-film / Shutterstock

The research team observed a sharp decrease in the spike protein (SP) IgG antibody six months after vaccination compared to levels at three weeks after the second vaccine dose. However, the decrease in the mixing index correlates poorly with the observed cellular immune response.

A hard copy of the research paper is available at medRxiv* Server while the article is subject to peer review.

background

Vaccination has provided a powerful strategy to control the coronavirus 2019 (COVID-19) epidemic. Pfizer-BioNTech’s BNT162b2 vaccine has become the first vaccine to receive emergency approval from the World Health Organization (WHO) for use against SARS-CoV-2.

Phase III trials for most vaccines have shown high efficacy. However, reports of the long-term decline in vaccine efficacy and the occurrence of paranormal infections have created a major concern around the world. Most vaccines are said to show a decrease in efficacy six months after vaccination. However, reports indicate that the effectiveness of the vaccine in preventing severe disease continues at high levels.

The decrease in vaccine efficacy can be attributed to a decrease in antibody titer or humoral immunity. However, cellular immunity may play a larger role in preventing acute COVID-19 than is yet understood.

What did the researchers do?

The study was conducted on 98 health care workers from Yokohama City University Hospital, Japan, who received two doses of BNT162b2 vaccine from March to April 2021.

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

Subsequently, a 50% neutralization titer (NT50) was calculated from a neutralization titer test that used an HIV-based, high SARS-CoV-2 pseudovirus.

In addition, the SARS-CoV-2-specific T-cell response was assessed in the form of a spot-forming cell (SFC) count by interferon (IFN)-ELISpot assay to assess cellular immune status at six months after vaccination.

What did the researchers find?

humoral immune index

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

A similar trend was observed for NT50, which also showed a significant decrease in GMT from 680.4 (95% CI; 588.0–787.2) at three weeks to 130.4 (95% CI; 104.2–163.1) at 6 months.

There were four patients with a history of penetrating injuries that occurred after completion of the second vaccine dose. In these, the SP IgG index ranged from 146.1 to 459.1, while NT50 ranged from 1631 to 8756 at six months. The elevated autoantibodies observed in these patients is thought to be due to the superinfections.

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

cellular immune index

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

A previous study 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 the current study was 84 SFC/106 PBMCs at six months after vaccination. The decline in cellular immunity was slower than that of the antibody titer, indicating that it is less negatively correlated with age, and may explain its long-term effect in protecting against infection with the acute form of the disease.

*Important note

medRxiv It publishes preliminary scientific reports that have not been peer-reviewed and therefore should not be considered conclusive, guide clinical practice/health-related behaviour, or be treated as established information.

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