Safety and immunogenicity of inactivated SARS-CoV-2 vaccines in people with gastrointestinal cancer

Abstract

Objectives: This study aimed to evaluate the safety and immunogenicity of inactivated COVID-19 vaccines in patients with gastrointestinal cancer (GI) cancer. The role of memory B cells (MBCs) in the humoral response to COVID-19 vaccination was also investigated.

Methods: In this prospective observational study, GI cancer patients and healthy individuals who had received 2 doses of inactivated COVID-19 vaccines were included. The data regarding adverse effects, serum anti-receptor binding domain (RBD)-IgG, neutralizing antibodies (NAbs), and frequencies of MBCs were collected prospectively.

Results: The inactivated COVID-19 vaccines were safe and well tolerated. Serum anti-RBG-IgG and NAbs were lower for cancer patients. Old age, high ASA score, and receiving active chemotherapy were risk factors for lower antibody titers. The frequencies of activated and resting MBCs decreased in (17.45% vs 38.11%, P = 0.002; 16.98% vs 34.13%, P = 0.023), while the frequencies of intermediate and atypical MBCs increased in cancer patients (40.06% vs 19.87%, P = 0.010; 25.47% vs 16.61%, P = 0.025). The serum antibody titer decreased gradually during follow-up but increased when a booster vaccine was given.

Conclusion: The inactivated COVID-19 vaccines were well tolerated in patients with GI cancer but with lower immunogenicity. The subpopulations of MBCs were disordered in cancer patients, and a booster vaccine may be prioritized for them.

Keywords: COVID-19; Inactivated vaccine; Memory B cells.

Figure 1

Flowchart of the study.

Figure 2

Antibody responses to inactivated SARS-COV-2 vaccines in patients with gastrointestinal cancer and healthy controls. The titers and seropositivity rate of anti-RBD-IgG (a-b) and NAbs (c-d) in cancer patients and healthy controls. The anti-RBD-IgG (e) and NAbs (f) titers are presented according to different numbers of days post vaccination. The trendlines were generated using a single linear model fit, and the shaded area represents the confidence interval for each fit with a 95% level of confidence. The correlation between the two antibodies (g) The horizontal dotted lines represent the limit of detection. The error bars represent the median (IQR). *P < 0.05, **P < 0.01. IQR = interquartile range; Nabs = neutralizing antibodies; RBD = receptor binding domain.

Figure 3

Antibody and specific MBC responses to inactivated SARS-COV-2 vaccines in participants of different ages. Subgroup analysis of the titers and seropositivity rate of anti-receptor binding domain (RBD)-IgG (a-b) and NAbs (c-d) in participants according to age. The frequencies of RBD-specific MBCs (e), resting MBCs (f), intermediate MBCs (g), activated MBCs (h), and atypical MBCs (i) in participants of different ages. The horizontal dotted lines represent the limit of detection. The error bars represent the median (IQR). *P < 0.05. MBCs = memory B-cell; Nabs = neutralizing antibodies; RBD = receptor binding domain.

Figure 4

Antibody and specific MBC responses to SARS-COV-2 vaccines in GI cancer patients with different ASA stages. Subgroup analysis of the titers and seropositivity rate of anti- RBD-IgG (a-b) and NAbs (c-d) in cancer patients with different ASA stages. The frequencies of RBD-specific MBCs (e), resting MBCs (f), intermediate MBCs (g), activated MBCs (h), and atypical MBCs (i) in cancer patients with different ASA stages. The horizontal dotted lines represent the limit of detection. The error bars represent the median (IQR). *P < 0.05, **P < 0.01, ***P < 0.001. MBCs = memory B-cell; Nabs = neutralizing antibodies; IQR = interquartile range; RBD = receptor binding domain.

Figure 5

Antibody and specific MBC responses to SARS-COV-2 vaccines in GI cancer patients with different treatments. The titers and seropositivity rate of anti-RBD-IgG (a-b) and NAbs (c-d) in cancer patients with different treatment statuses. The frequencies of RBD-specific MBCs (e), resting MBCs (f), intermediate MBCs (g), activated MBCs (h), and atypical MBCs (i) in cancer patients with different treatment statuses. The horizontal dotted lines represent the limit of detection. The error bars represent the median (IQR). *P < 0.05, **P < 0.01. GI = gastrointestinial; MBCs = memory B-cell; NAbs = neutralizing antibodies; IQR= interquartile range; RBD = receptor binding domain.

Figure 6

Antibody and specific MBC responses to SARS-COV-2 vaccines in GI cancer patients with or without chemotherapy. The titers and seropositivity rate of anti-RBD-IgG (a-b) and NAbs (c-d) in cancer patients with or without chemotherapy. The frequencies of RBD-specific MBCs (e), resting MBCs (f), intermediate MBCs (g), activated MBCs (h), and atypical MBCs (i) in cancer patients with or without chemotherapy. The horizontal dotted lines represent the limit of detection. The error bars represent the median (IQR). *P < 0.05, **P < 0.01. GI = gastrointestinial; MBCs = memory B-cell; Nabs = neutralizing antibodies; IQR = interquartile range; RBD = receptor binding domain.

Figure 7

Specific MBC responses to SARS-COV-2 vaccines in GI cancer patients and healthy controls. The frequencies of RBD-specific MBCs (a), rMBCs (b), intMBCs (c), actMBCs (d), and atyMBCs (e) in cancer patients and healthy controls. The change in frequencies of RBD-specific MBCs (f), rMBCs (g), intMBCs (h), actMBCs (i), and atyMBCs (j) over time in cancer patients and healthy controls. The error bars represent the median (IQR). The trendlines were generated using a single linear model fit, and the shaded area represents the confidence interval for each fit with a 95% confidence level of confidence. *P < 0.05, **P < 0.01. actMBCs = activated MBCs; atyMBCs = atypical MBCs; GI = gastrointestinial; Nabs = neutralizing antibodies; IQR = interquartile range; intMBCs = intermediate MBCs; MBCs = memory B-cell; RBD = receptor binding domain; rMBCs = resting MBCs.

Figure 8

Antibody responses to SARS-COV-2 vaccines in GI cancer patients and healthy controls during follow-up. The concentrations of anti-RBD-IgG (a, c) and NAbs (b, d) during follow-up. The red dots indicate samples collected before the BV, and the green dots indicate samples collected after BV (a-b). The blue dots indicate samples collected before BV, and the orange dots indicate samples collected after BV (c-d). The horizontal dotted lines represent the limit of detection. GI = gastrointestinial; BV = booster vaccine; NAbs = neutralizing antibodies; RBD = receptor binding domain.

Figure 9

Specific MBC responses to SARS-COV-2 vaccines in GI cancer patients and healthy controls during follow-up. The frequencies of RBD-specific MBCs (a, f), resting MBCs (b, g), intermediate MBCs (c, h), activated MBCs (d, i), and atypical MBCs (e, j) during follow-up. GI = gastrointestinial; MBCs= memory B-cell; RBD = receptor binding domain