scholarly journals Adaptive immunity and neutralizing antibodies against SARS-CoV-2 variants of concern following vaccination in patients with cancer: The CAPTURE study

2021 ◽  
Author(s):  
Annika Fendler ◽  
Scott Shepherd ◽  
Lewis Au ◽  
Katalin Wilkinson ◽  
Mary Wu ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Neutralizing Antibodies ◽  
Hematological Malignancies ◽  
Neutralizing Antibody ◽  
Patients With Cancer ◽  
Cell Responses ◽  
Solid Malignancies ◽  
Antibody Titers ◽  
Cancer Types ◽  
Anti Cd20

Abstract CAPTURE (NCT03226886) is a prospective cohort study of COVID-19 immunity in patients with cancer. Here we evaluated 585 patients following administration of two doses of BNT162b2 or AZD1222 vaccines, administered 12 weeks apart. Seroconversion rates after two doses were 85% and 59% in patients with solid and hematological malignancies, respectively. A lower proportion of patients had detectable neutralizing antibody titers (NAbT) against SARS-CoV-2 variants of concern (VOCs) vs wild-type (WT). Patients with hematological malignancies were more likely to have undetectable NAbT and had lower median NAbT vs solid cancers against both WT and VOCs. In comparison with individuals without cancer, patients with haematological, but not solid, malignancies had reduced NAb responses. Seroconversion showed poor concordance with NAbT against VOCs. Prior SARS-CoV-2 infection boosted NAb response including against VOCs, and anti-CD20 treatment was associated with undetectable NAbT. Vaccine-induced T-cell responses were detected in 80% of patients, and were comparable between vaccines or cancer types. Our results have implications for the management of cancer patients during the ongoing COVID-19 pandemic.

scholarly journals Adaptive immunity and neutralizing antibodies against SARS-CoV-2 variants of concern following vaccination in patients with cancer: the CAPTURE study

Nature Cancer ◽  
2021 ◽  
Author(s):  
Annika Fendler ◽  
Scott T. C. Shepherd ◽  
Lewis Au ◽  
Katalin A. Wilkinson ◽  
Mary Wu ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Hematological Malignancies ◽  
Neutralizing Antibody ◽  
Immune Monitoring ◽  
Wild Type ◽  
Patients With Cancer ◽  
Cell Responses ◽  
Solid Malignancies ◽  
Cancer Types ◽  
Anti Cd20

AbstractCoronavirus disease 2019 (COVID-19) antiviral response in a pan-tumor immune monitoring (CAPTURE) (NCT03226886) is a prospective cohort study of COVID-19 immunity in patients with cancer. Here we evaluated 585 patients following administration of two doses of BNT162b2 or AZD1222 vaccines, administered 12 weeks apart. Seroconversion rates after two doses were 85% and 59% in patients with solid and hematological malignancies, respectively. A lower proportion of patients had detectable titers of neutralizing antibodies (NAbT) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) versus wild-type (WT) SARS-CoV-2. Patients with hematological malignancies were more likely to have undetectable NAbT and had lower median NAbT than those with solid cancers against both SARS-CoV-2 WT and VOC. By comparison with individuals without cancer, patients with hematological, but not solid, malignancies had reduced neutralizing antibody (NAb) responses. Seroconversion showed poor concordance with NAbT against VOC. Previous SARS-CoV-2 infection boosted the NAb response including against VOC, and anti-CD20 treatment was associated with undetectable NAbT. Vaccine-induced T cell responses were detected in 80% of patients and were comparable between vaccines or cancer types. Our results have implications for the management of patients with cancer during the ongoing COVID-19 pandemic.

scholarly journals Functional antibody and T-cell immunity following SARS-CoV-2 infection, including by variants of concern, in patients with cancer: the CAPTURE study

2021 ◽  
Author(s):  
Annika Fendler ◽  
Lewis Au ◽  
Scott Shepherd ◽  
Fiona Byrne ◽  
Maddalena Cerrone ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Cellular Responses ◽  
Patients With Cancer ◽  
Cell Immunity ◽  
Clinical Annotation ◽  
Antibody Titers ◽  
Antibody Levels ◽  
Immune Profiling ◽  
Reactive Antibody

Abstract Patients with cancer have higher COVID-19 morbidity and mortality. Here we present the prospective CAPTURE study (NCT03226886) integrating longitudinal immune profiling with clinical annotation. Of 357 patients with cancer, 118 were SARS-CoV-2-positive, 94 were symptomatic and 2 patients died of COVID-19. In this cohort, 83% patients had S1-reactive antibodies, 82% had neutralizing antibodies against WT, whereas neutralizing antibody titers (NAbT) against the Alpha, Beta, and Delta variants were substantially reduced. Whereas S1-reactive antibody levels decreased in 13% of patients, NAbT remained stable up to 329 days. Patients also had detectable SARS-CoV-2-specific T cells and CD4+ responses correlating with S1-reactive antibody levels, although patients with hematological malignancies had impaired immune responses that were disease and treatment-specific, but presented compensatory cellular responses, further supported by clinical. Overall, these findings advance the understanding of the nature and duration of immune response to SARS-CoV-2 in patients with cancer.

scholarly journals Control of SARS-CoV-2 infection after Spike DNA or Spike DNA+Protein co-immunization in rhesus macaques

2021 ◽  
Author(s):  
Margherita Rosati ◽  
Mahesh Agarwal ◽  
Xintao Hu ◽  
Santhi Devasundaram ◽  
Dimitris Stellas ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Protective Efficacy ◽  
Rhesus Macaques ◽  
Neutralizing Antibody ◽  
Anatomical Site ◽  
Cell Responses ◽  
Cellular Immune Responses ◽  
Antibody Titers ◽  
Cellular Immune

The speed of development, versatility and efficacy of mRNA-based vaccines have been amply demonstrated in the case of SARS-CoV-2. DNA vaccines represent an important alternative since they induce both humoral and cellular immune responses in animal models and in human trials. We tested the immunogenicity and protective efficacy of DNA-based vaccine regimens expressing different prefusion-stabilized SARS-CoV-2 Spike antigens upon intramuscular injection followed by electroporation in rhesus macaques. Different Spike DNA vaccine regimens induced antibodies that potently neutralized SARS-CoV-2 in vitro and elicited robust T cell responses. The DNA-only vaccine regimens were compared to a regimen that included co-immunization of Spike DNA and protein in the same anatomical site, the latter of which showed significant higher antibody responses. All vaccine regimens led to control of SARS-CoV-2 intranasal/intratracheal challenge and absence of virus dissemination to the lower respiratory tract. Vaccine-induced binding and neutralizing antibody titers and antibody-dependent cellular phagocytosis inversely correlated with transient virus levels in the nasal mucosa. Importantly, the Spike DNA+Protein co-immunization regimen induced the highest binding and neutralizing antibodies and showed the strongest control against SARS-CoV-2 challenge in rhesus macaques.

scholarly journals Preclinical Immunological Evaluation of an Intradermally Administered Heterologous Vaccine Against SARS-CoV-2 Variants

2021 ◽  
Author(s):  
Qihan Li ◽  
Shengtao Fan ◽  
Kang Xiao ◽  
Dandan Li ◽  
Heng Zhao ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Challenge Test ◽  
Neutralizing Antibody ◽  
Cell Responses ◽  
Recent Emergence ◽  
New Strategy ◽  
Antibody Titers ◽  
Immune Efficacy ◽  
Immunological Evaluation ◽  
Intradermal Route

Abstract The recent emergence of new variants in the COVID-19 pandemic has led to new requirements for vaccines, with a focus on the capacity of vaccines to elicit high levels of neutralizing antibodies with specific recognition of S antigen variants based on the characterized vaccines licensed for use. A new strategy involving a heterologous vaccine composed of one or two doses of inactivated vaccine and a boost with the S1 protein with mutations (K-S) administered via the intradermal route was designed in this work and was found to improve immune efficacy by increasing neutralizing antibody titers and promoting specific T cell responses against 5 variants of the RBD peptide. A viral challenge test with the B.1.617.2 (Delta) variant confirmed that the both schedules of “1+1” and “2+1” administration ensured a clinical protective effect against this strain. All of these results not only suggested the feasibility of our strategy for protecting against new variants but also provided a technical pathway to enhance the anamnestic immune response in the immunized population.

scholarly journals COVID-19-Vaccination Prioritization in Patients with Cancer

2021 ◽  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
B Cell ◽  
Cancer Patients ◽  
Hematological Malignancies ◽  
Performance Status ◽  
Poor Performance ◽  
Poor Performance Status ◽  
Patients With Cancer ◽  
Cell Responses

In patients with cancer, SARS-CoV-2 (COVID-19) can contribute to increasing morbidity and mortality and decreased survival was found in patients with hematological and intrathoracic malignancies, poor performance status, comorbidities, and increased age. Patients with hematological malignancies who were treated with stem cell transplantation and anti-CD-20 antibody demonstrated lower rates of seroconversion, compared to COVID-19-infected-cancer patients. Patients with hematological malignancies might have substantially compromised B-cell and T-cell responses.

scholarly journals Glycan-masking spike antigen in NTD and RBD elicits broadly neutralizing antibodies against SARS-CoV-2 variants

2021 ◽  
Author(s):  
Wei-Shuo Lin ◽  
I-Chen Chen ◽  
Hui-Chen Chen ◽  
Yi-Chien Lee ◽  
Suh-Chin Wu
Keyword(s):  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Fold Increase ◽  
Vaccine Antigen ◽  
Broadly Neutralizing Antibodies ◽  
Neutralization Titer ◽  
Cell Responses ◽  
Folded Structure ◽  
Antibody Titers ◽  
The Impact

Glycan-masking the vaccine antigen by mutating the undesired antigenic sites with an additional N-linked glycosylation motif can refocus B-cell responses to desired/undesired epitopes, without affecting the antigen overall-folded structure. This study examine the impact of glycan-masking mutants of the N-terminal domain (NTD) and receptor-binding domain (RBD) of SARS-CoV-2, and found that the antigenic design of the S protein increases the neutralizing antibody titers against the Wuhan-Hu-1 ancestral strain and the recently emerged SARS-CoV-2 variants Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2). Our results demonstrated that the use of glycan-masking Ad-S-R158N-Y160T in the NTD elicited a 2.8-fold, 6.5-fold, and 4.6-fold increase in the IC-50 NT titer against the Alpha (B.1.1.7), Beta (B.1.351) and Delta (B.1.617.2) variants, respectively. Glycan-masking of Ad-S-D428N in the RBD resulted in a 3.0-fold and 2.0-fold increase in the IC50 neutralization titer against the Alpha (B.1.1.7) and Beta (B.1.351) variants, respectively. The use of glycan-masking in Ad-S-R158N-Y160T and Ad-S-D428N antigen design may help develop universal COVID-19 vaccines against current and future emerging SARS-CoV-2 variants.

scholarly journals Glycan Masking of Epitopes in the NTD and RBD of the Spike Protein Elicits Broadly Neutralizing Antibodies Against SARS-CoV-2 Variants

2021 ◽  
Vol 12 ◽  
Author(s):  
Wei-Shuo Lin ◽  
I-Chen Chen ◽  
Hui-Chen Chen ◽  
Yi-Chien Lee ◽  
Suh-Chin Wu
Keyword(s):  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Fold Increase ◽  
Vaccine Antigen ◽  
Broadly Neutralizing Antibodies ◽  
Neutralization Titer ◽  
Cell Responses ◽  
Folded Structure ◽  
Antibody Titers ◽  
The Impact

Glycan-masking the vaccine antigen by mutating the undesired antigenic sites with an additional N-linked glycosylation motif can refocus B-cell responses to desired epitopes, without affecting the antigen’s overall-folded structure. This study examined the impact of glycan-masking mutants of the N-terminal domain (NTD) and receptor-binding domain (RBD) of SARS-CoV-2, and found that the antigenic design of the S protein increases the neutralizing antibody titers against the Wuhan-Hu-1 ancestral strain and the recently emerged SARS-CoV-2 variants Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2). Our results demonstrated that the use of glycan-masking Ad-S-R158N/Y160T in the NTD elicited a 2.8-fold, 6.5-fold, and 4.6-fold increase in the IC-50 NT titer against the Alpha (B.1.1.7), Beta (B.1.351) and Delta (B.1.617.2) variants, respectively. Glycan-masking of Ad-S-D428N in the RBD resulted in a 3.0-fold and 2.0-fold increase in the IC-50 neutralization titer against the Alpha (B.1.1.7) and Beta (B.1.351) variants, respectively. The use of glycan-masking in Ad-S-R158N/Y160T and Ad-S-D428N antigen design may help develop universal COVID-19 vaccines against current and future emerging SARS-CoV-2 variants.

scholarly journals Antibodies elicited by SARS-CoV-2 infection and boosted by vaccination neutralize an emerging variant and SARS-CoV-1

2021 ◽  
Author(s):  
Leonidas Stamatatos ◽  
Julie Czartoski ◽  
Yu-Hsin Wan ◽  
Leah J. Homad ◽  
Vanessa Rubin ◽  
...  
Keyword(s):  
South Africa ◽  
Immune Response ◽  
Monoclonal Antibodies ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Fold Increase ◽  
Cd4 T Cell ◽  
Cell Responses ◽  
Previous Infection ◽  
Antibody Titers

AbstractThe emergence of SARS-CoV-2 variants raises concerns about their resistance to neutralizing antibodies elicited from previous infection, or from vaccination. Here we examined whether sera and monoclonal antibodies from convalescent donors, prior to and following a single immunization with the Pfizer or Moderna mRNA vaccines, neutralize the Wuhan-Hu-1 strain and a variant, B.1.351 from South Africa. Pre-vaccination sera weakly neutralized Wuhan-Hu-1 and sporadically neutralized B.1.351. Immunization with either vaccine generated anamnestic B and CD4+ T cell responses and a 1000-fold increase in neutralizing antibody titers against both strains and SARS-CoV-1. Neutralization was likely due to anti-RBD and anti-S2 antibodies. Our study highlights the importance of vaccination of both uninfected and of previously infected subjects, as the elicited immune response will neutralize distinct viral strains.

scholarly journals Functional antibody and T cell immunity following SARS-CoV-2 infection, including by variants of concern, in patients with cancer: the CAPTURE study

Nature Cancer ◽  
2021 ◽  
Author(s):  
Annika Fendler ◽  
Lewis Au ◽  
Scott T. C. Shepherd ◽  
Fiona Byrne ◽  
Maddalena Cerrone ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Wild Type ◽  
Patients With Cancer ◽  
Cell Immunity ◽  
Clinical Annotation ◽  
Antibody Titers ◽  
Antibody Levels ◽  
Immune Profiling ◽  
Reactive Antibody

AbstractPatients with cancer have higher COVID-19 morbidity and mortality. Here we present the prospective CAPTURE study, integrating longitudinal immune profiling with clinical annotation. Of 357 patients with cancer, 118 were SARS-CoV-2 positive, 94 were symptomatic and 2 died of COVID-19. In this cohort, 83% patients had S1-reactive antibodies and 82% had neutralizing antibodies against wild type SARS-CoV-2, whereas neutralizing antibody titers against the Alpha, Beta and Delta variants were substantially reduced. S1-reactive antibody levels decreased in 13% of patients, whereas neutralizing antibody titers remained stable for up to 329 days. Patients also had detectable SARS-CoV-2-specific T cells and CD4+ responses correlating with S1-reactive antibody levels, although patients with hematological malignancies had impaired immune responses that were disease and treatment specific, but presented compensatory cellular responses, further supported by clinical recovery in all but one patient. Overall, these findings advance the understanding of the nature and duration of the immune response to SARS-CoV-2 in patients with cancer.

scholarly journals Prioritization of Covid-19 Vaccination in Patients with Cancer

2021 ◽  
Vol 6 (3) ◽  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
B Cell ◽  
Cancer Patients ◽  
Hematological Malignancies ◽  
Performance Status ◽  
Poor Performance ◽  
Poor Performance Status ◽  
Patients With Cancer ◽  
Cell Responses

In patients with cancer, SARS-CoV-2 (COVID-19) can contribute to increasing morbidity and mortality and decreased survival was found in patients with hematological and intrathoracic malignancies, poor performance status, comorbidities, and increased age. Patients with hematological malignancies who were treated with stem cell transplantation and anti-CD-20 antibody demonstrated lower rates of seroconversion, compared to COVID-19-infected-cancer patients. Patients with hematological malignancies might have substantially compromised B-cell and T-cell responses.

Sign in / Sign up

Export Citation Format

Share Document