Cellular and Humoral Immune Responses to Vaccination for COVID-19 Are Negatively Impacted by Senescent T Cells: A Case Report

Abstract

Background: Herein, we aimed to follow up on the cellular and humoral immune responses of a group of individuals who initially received the CoronaVac vaccine, followed by a booster with the Pfizer vaccine.

Methods: Blood samples were collected: before and 30 days after the first CoronaVac dose; 30, 90, and 180 days after the second CoronaVac dose, and also 20 days after the booster with the Pfizer vaccine.

Results: Whilst the positivity to gamma interferon-type cellular response increased after the first CoronaVac dose, neutralizing and IgG antibody levels only raised 30 days after the second dose, followed by a drop in these responses after 90 and 180 days. The booster with the Pfizer vaccine elicited a robust cellular and humoral response. A higher number of double-negative and senescent T cells, as well as increased pro-inflammatory cytokines levels were found in the participants with lower humoral immune responses.

Conclusion: CoronaVac elicited an early cellular response, followed by a humoral response, which dropped 90 days after the second dose. The booster with the Pfizer vaccine significantly enhanced these responses. Furthermore, a pro-inflammatory systemic status was found in volunteers who presented senescent T cells, which could putatively impair the immune response to vaccination.

Keywords: CoronaVac vaccine; Pfizer vaccine; cell senescence; immunophenotyping; inflammation; neutralizing antibodies.

Figure 1

Follow-up of eight volunteers from pre-CoronaVac vaccine to Pfizer booster. (A) SARS-CoV-2 Surrogate Virus % Neutralization Test, sVNT (cPass™ GenScript USA, Inc., Piscataway NJ, USA). There was no difference between the results of neutralizing antibody tests between the sVNT and CPE-VNT methods, p > 0.131. (B) Automated chemiluminescent assay (CMIA) SARS-CoV-2 IgG II Quant, performed on the ARCHITECT i System (Abbott Ireland Diagnostics Division).

Figure 2

Activated T cells are related to the production of neutralizing antibodies, and, on the other hand, senescent T cell populations can impair this production by volunteers vaccinated with CoronaVac. Whole blood collected before first Coronavac dose was analyzed by flow cytometry. Analysis were performed using FlowJo software. A total of 10,000 lymphocytes from each volunteer were concatenated before performing unsupervised analysis. Neutralizing antibody production was evaluated after first (22 to 34 days, time 1), second (30 to 38 days, time 2), and 90 days (88 to 103 days, time 3) after second dose Coronavac vaccine. (A) Colormap graphs for lymphocytes populations present in whole blood from volunteers before Coronavac vaccination. (B) UMAP graphs showing volunteers that produced (R—blue) or did not produce (NR—red) neutralizing antibodies after Coronavac vaccination. (C) Top: UMAP graph and histograms showing the cell populations found in responder (Pop 2—green) or non-responder (Pop 1—purple and Pop 3—orange) volunteers. Down: Frequencies of populations 1-3 for R and NR 90 days after second dose Coronavac vaccine, including individual values, median, and interquartile range. (D) UMAP graphs representative of each volunteer individually, considering R and NR 90 days after second dose Coronavac vaccine. EM = effector memory; Eff = effector; DN = double-negative.