Immune Response after 2 Doses of BNT162b2 mRNA COVID-19 Vaccinations in Children and Adolescents with Cancer and Hematologic Diseases

Background: The BNT162b2 mRNA COVID-19 vaccine has been administered to children and adolescents with cancer and hematologic diseases since they are at high risk of manifesting severe symptoms if they have COVID-19 infection but the adequate immune response after vaccination in these immunocompromised patients are questionable.Objective: To evaluate the immune response of children and adolescents with cancer and hematologic diseases after receiving 2 doses of the BNT162b2 mRNA COVID-19 vaccine. Methods: This is a prospective cohort study of patients with cancer and hematologic disease, who aged 12- 18 years old and received 2 doses the BNT162b2 vaccines at 4 weeks apart were enrolled. Immunogenicity was determined by measuring serum anti-SARS-CoV-2 immunoglobulin antibodies directed against the receptor binding domain (RBD) of S1 domain of the spike protein (Anti S-RBD), surrogated viral neutralization test (sVNT) of SARS-CoV-2 and Delta strain. Blood samples were collected and analyzed at 4 and 12 weeks after vaccination. The seroprotective rate was defined as sVNT ≥ 68%. Results: From Oct 2021 to Jan 2022, 43 children were enrolled, 21 were on-therapy and 22 were off-therapy. 25 were hematologic malignancy, 15 solid tumor and 3 hematologic diseases with immunosuppressive drugs. The GMT (95%CI) of a anti S-RBD IgG level at 4 weeks after vaccination were 56.05 (13.2,238.2) and 3633 (2689,4908) BAU/mL in on-therapy and off-therapy group, respectively, p<0.001. The sVNT (95%CI) of delta strain were 26% (5.85-73.55%) and 97.05% (96.0-97.4%) as the seroprotective level which were 33.3% in on-therapy group and 100% in off-therapy group (p<0.001). 14 children in on-therapy group need an additional dose. Conclusion: After complete vaccination, the seroprotective rate and antibody level in pediatric and adolescent patients with cancer and hematologic disease who receive immunosuppressive agents are quite low, compared with patients who had complete treatment. Additional dose of primary series should be offered.     

Immunogenicity of SARS-CoV-2 messenger RNA vaccines in patients with cancer

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Antibody response to three-dose anti-SARS-CoV-2 mRNA-vaccination in treated solid cancer patients

Solid cancer patients are at higher risk of SARS-CoV-2 infection and severe complications. Moreover, vaccine-induced antibody response is impaired in patients on anticancer treatment. In this retrospective, observational, hypothesis-generating, cohort study, we assessed the antibody response to the third dose of mRNA vaccine in a convenience sample of patients on anticancer treatment, comparing it to that of the primary two-dose cycle. Among 99 patients included, 62.6% were ≥60 years old, 32.3% males, 67.7% with advanced disease. Exactly 40.4% were receiving biological therapy, 16.2% chemotherapy only and 7.1% both treatments. After the third dose, seroconversion rate seems to increase significantly, especially in non-responders to two doses. Heterologous vaccine-type regimen (two-dose mRNA-1273 and subsequent tozinameran or vice versa) results in higher antibody levels. This explorative study suggests that repeated doses of mRNA-vaccines could be associated with a better antibody response in this population. Furthermore, heterologous vaccine-type three-dose vaccination seems more effective in this population. Since this is a hypothesis-generating study, adequately statistically powered studies should validate these results.     

SARS-CoV-2 Vaccine Immunogenicity in Patients with Gastrointestinal Cancer Receiving Systemic Anti-Cancer Therapy

IntroductionPatients with gastrointestinal (GI) cancers have an increased risk of serious complications and death from SARS-CoV-2 infection. The immunogenicity of vaccines in patients with GI cancers receiving anti-cancer therapies is unclear. We conducted a prospective study to evaluate the prevalence of neutralizing antibodies in a cohort of GI cancer patients receiving chemotherapy following SARS-CoV-2 vaccination.Materials and MethodsBetween September 2020 and April 2021, patients with cancer undergoing chemotherapy were enrolled. At baseline (day 0), days 28, 56, and 84, we assessed serum antibodies to SARS-CoV-2 spike (anti-S) and anti-nucleocapsid (anti-NP) and concomitantly assessed virus neutralization using a pseudovirus neutralization assay. Patients received either the Pfizer/BioNTech BNT162b2, or the Oxford/AstraZeneca ChAdOx1 vaccine.ResultsAll 152 patients enrolled had a prior diagnosis of cancer; colorectal (n = 80, 52.6%), oesophagogastric (n = 38, 25.0%), and hepato pancreatic biliary (n = 22, 12.5%). Nearly all were receiving systemic anti-cancer therapy (99.3%). Of the 51 patients who did not receive a vaccination prior to, or during the study, 5 patients had detectable anti-NP antibodies. Ninety-nine patients received at least one dose of vaccine prior to, or during the study. Within 19 days following the first dose of vaccine, 30.0% had anti-S detected in serum which increased to 70.2% at days 20-39. In the 19 days following a second dose, anti-S positivity was 84.2% (32/38). However, pseudovirus neutralization titers (pVNT80) decreased from days 20 to 39.ConclusionDespite the immunosuppressive effects of chemotherapy, 2 doses of SARS-CoV-2 vaccines are able to elicit a protective immune response in patients’ ongoing treatment for gastrointestinal cancers. Decreases in pseudoviral neutralization were observed after 20-39 days, re-affirming the current recommendation for vaccine booster doses.Clinical Trial Registration Number{"type":"clinical-trial","attrs":{"text":"NCT04427280","term_id":"NCT04427280"}}NCT04427280.     

Immunogenicity of two doses of inactive COVID-19 vaccine and third booster dose mRNA vaccine in patients with cancer receiving active systemic therapy

We aimed to evaluate the seroconversion rates after two doses of inactive COVID-19 vaccine (CoronaVac) and the benefit of a third dose mRNA vaccine booster in patients with cancer receiving active treatment. Patients with solid tumors receiving active treatment (n = 101) and patients with no-cancer (n = 48) as the control group were included in the study. All the patients and controls had received two doses of CoronaVac and a third booster dose of the mRNA vaccine (Bnt162b2). Anti-SARS-CoV-2 Spike Receptor Binding Domain IgG antibody levels after the second and third dose were measured with quantitative ELISA. The median age of the patients was 66 (IQR 60-71). 79% of the patients were receiving chemotherapy, and 21% were receiving immunotherapy at the time of vaccination. Antibody levels measured after two doses of CoronaVac were significantly lower in patients with cancer than in the control group (median 0 μg/ml [IQR 0-1.17 μg/ml] vs median 0.91 μg/ml [IQR 0-2.24 μg/ml], respectively, P = .002). Seropositivity rates were 46.5% in patients with cancer and 72.9% in the control group (P = .002). Antibody measurement was performed in 26 patients after the third dose. Seroconversion rate increased from 46.5% to 88.5% (P < .001), and the antibody titers significantly increased with the third-dose booster (median 0 μg/ml [IQR 0-1.17 μg/ml] after two doses vs 12.6 μg/ml [IQR 1.8-69.1 μg/ml] after third booster dose, P < .001). Immunogenicity of CoronaVac is low in patients with cancer receiving active treatment, and administering a third dose of an mRNA vaccine is effective in terms of improving seroconversion rates.     

Seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with cancer and the impact of anti-tumor treatment on antibodies

Objective The aim of this study was to examine the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among patients with cancer and followed up changes in SARS-CoV-2-specific antibodies to explore the impact of anti-tumor treatment in patients. Methods Patients with cancer who visited the Outpatient Clinic of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China between March 9 and April 30, 2020 were enrolled in this retrospective cohort study. SARS-CoV-2 immunoglobulin (Ig) G, IgM, and viral load at various time points during the disease course were determined. Results We examined the serological results of 779 patients with cancer. The overall seroprevalence (IgG-positive or IgM-positive) rate of SARS-CoV-2 was 3.4％. The probability of seropositivity was significantly higher in patients with gastric cancer than in those without gastric cancer (odds ratio: 6.349, 95％ confidence interval: 2.191–18.396). Follow-up data showed that SARS-CoV-2 IgM and IgG levels decreased and the polymerase chain reaction test result remained negative in seropositive patients with cancer. Conclusion This study investigated the seroprevalence of SARS-CoV-2 in coronavirus disease (COVID-19)-positive patients with cancer in Wuhan, China. The seropositivity in patients with cancer was lower than or similar to that in the general population. Irrespective of anti-tumor therapy, the levels of SARS-CoV-2 antibodies decreased in these patients. More studies are needed to better understand the impact of anti-tumor therapy on change in the levels of SARS-CoV-2 antibodies.     

Neutralization breadth of SARS-CoV-2 viral variants following primary series and booster SARS-CoV-2 vaccines in patients with cancer

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