Cancer Res Treat.  2023 Jul;55(3):746-757. 10.4143/crt.2022.1541.

Immunogenicity and Safety of Vaccines against Coronavirus Disease in Actively Treated Patients with Solid Tumors: A Prospective Cohort Study

• Baek YJ
• Lee YJ
• Park SR
• Kim KH
• Beom SH
• Lee Ck
• Shin SJ
• Rha SY
• Kim S
• Lee KH
• Kim JH
• Jeong SJ
• Ku NS
• Choi JY
• Yeom JS
• Jung M
• Ahn JY

• KMID: 2544158
• DOI: http://doi.org/10.4143/crt.2022.1541

Abstract

Purpose
We aimed to assess the humoral response to and reactogenicity of coronavirus disease 2019 (COVID-19) vaccination according to the vaccine type and to analyze factors associated with immunogenicity in actively treated solid cancer patients (CPs).
Materials and Methods
Prospective cohorts of CPs, undergoing anticancer treatment, and healthcare workers (HCWs) were established. The participants had no history of previous COVID-19 and received either mRNA-based or adenovirus vector–based (AdV) vaccines as the primary series. Blood samples were collected before the first vaccination and after 2 weeks for each dose vaccination. Spike-specific binding antibodies (bAbs) in all participants and neutralizing antibodies (nAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wild-type, Delta, and Omicron variants in CPs were analyzed and presented as the geometric mean titer.
Results
Age-matched 20 HCWs and 118 CPs were included in the analysis. The bAb seroconversion rate and antibody concentrations after the first vaccination were significantly lower in CPs than in HCWs. After the third vaccination, antibody levels in CPs with a primary series of AdV were comparable to those in HCWs, but nAb titers against the Omicron variant did not quantitatively increase in CPs with AdV vaccine as the primary series. The incidence and severity of adverse reactions post-vaccination were similar between CPs and HCWs.
Conclusion
CPs displayed delayed humoral immune response after SARS-CoV-2 vaccination. The booster dose elicited comparable bAb concentrations between CPs and HCWs, regardless of the primary vaccine type. Neutralization against the Omicron variant was not robustly elicited following the booster dose in some CPs, implying the need for additional interventions to protect them from COVID-19.

Keyword

Immunogenicity; Reactogenicity; COVID-19 vaccine; Solid cancer; Chemotherapy

Figure

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  Fig. 1 Spike-specific binding antibody (S-specific Ab) concentrations following each vaccination. S-specific Ab concentrations following severe acute respiratory syndrome coronavirus 2 vaccine in the solid cancer patients (CPs) and healthcare workers (HCWs) (A) after vaccination in CPs and HCWs receiving either mRNA or adenovirus vector vaccine. Comparison of binding antibody concentrations between CPs and HCWs stratified by the type of primary vaccination set after the first vaccination (B), after the second vaccination (C), and after the third vaccination (D). Antibody levels are represented as U/mL, and described as geometric mean with 95% confidence interval. Statistical analyses within each group were performed using the 2-tailed Mann-Whitney test. The Ca-mRNA group received a primary set of mRNA vaccines (either BNT162b2 or mRNA-1273), and the Ca-AdV group received a primary set of adenovirus vector vaccines (AZD1222); HCW-mRNA and HCW-AdV are groups of age-matched HCWs who received a primary series of mRNA vaccines and adenovirus vector vaccines, respectively. Each circle indicates the reciprocal binding antibody titer. ns, no significance; *p < 0.05, **p < 0.01, ***p < 0.001.

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  Fig. 2 Neutralization titers against wild-type virus and the Delta and Omicron variants following the second and third vaccination in patients with solid cancers, in accordance with the type of primary series of vaccine. Antibody titers are described as geometric mean with 95% confidence interval. Significance was analyzed using the 2-tailed Mann-Whitney test between two groups. The Ca-mRNA group received a primary series of mRNA vaccines (either BNT162b2 or mRNA-1273) and the Ca-AdV group received a primary series of adenovirus vector vaccines (AZD1222). Each circle indicates the reciprocal binding antibody titer. ns, no significance; *p < 0.05, **p < 0.01.

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  Fig. 3 Reactogenicity after each vaccination with mRNA and adenoviral vector vaccine among cancer patients and healthcare workers (HCWs). Participants were questioned about the duration and severity of each symptom with grades, within 7 days following each dose of vaccine. To calculate the cumulative symptom scores, the scores were summed and adapted to severity: asymptomatic (grade 0), mild (below 4 scores, grade 1), moderate (below 8 scores, grade 2), and severe (> 8 scores, grade 3). Proportion of adverse reactions stratified by severity in each group was calculated.

Reference

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