Impaired neutralisation of SARS-CoV-2 delta variant in vaccinated patients with B cell chronic lymphocytic leukaemia

Abstract Background Immune suppression is a clinical feature of chronic lymphocytic leukaemia (CLL), and patients show increased vulnerability to SARS-CoV-2 infection and suboptimal antibody responses. Method We studied antibody responses in 500 patients following dual COVID-19 vaccination to assess the magnitude, correlates of response, stability and functional activity of the spike-specific antibody response with two different vaccine platforms. Results Spike-specific seroconversion post-vaccine was seen in 67% of patients compared to 100% of age-matched controls. Amongst responders, titres were 3.7 times lower than the control group. Antibody responses showed a 33% fall over the next 4 months. The use of an mRNA (n = 204) or adenovirus-based (n = 296) vaccine platform did not impact on antibody response. Male gender, BTKi therapy, prophylactic antibiotics use and low serum IgA/IgM were predictive of failure to respond. Antibody responses after CD20-targeted immunotherapy recovered 12 months post treatment. Post-vaccine sera from CLL patients with Spike-specific antibody response showed markedly reduced neutralisation of the SARS-CoV-2 delta variant compared to healthy controls. Patients with previous natural SARS-CoV-2 infection showed equivalent antibody levels and function as healthy donors after vaccination. Conclusions These findings demonstrate impaired antibody responses following dual COVID-19 vaccination in patients with CLL and further define patient risk groups. Furthermore, humoural protection against the globally dominant delta variant is markedly impaired in CLL patients and indicates the need for further optimisation of immune protection in this patient cohort.

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Antibody responses after first and second Covid-19 vaccination in patients with chronic lymphocytic leukaemia

Blood Cancer Journal ◽

10.1038/s41408-021-00528-x ◽

2021 ◽

Vol 11 (7) ◽

Author(s):

H. Parry ◽

G. McIlroy ◽

R. Bruton ◽

M. Ali ◽

C. Stephens ◽

...

Keyword(s):

Antibody Response ◽

Chronic Lymphocytic Leukaemia ◽

Specific Antibody ◽

Lymphocytic Leukaemia ◽

Vaccination Strategy ◽

Severe Infection ◽

Dried Blood Spots ◽

Iga Deficiency ◽

Antibody Responses ◽

Healthy Donors

AbstractB-cell chronic lymphocytic leukaemia (CLL) is associated with immunosuppression and patients are at increased clinical risk following SARS-CoV-2 infection. Covid-19 vaccines offer the potential for protection against severe infection but relatively little is known regarding the profile of the antibody response following first or second vaccination. We studied spike-specific antibody responses following first and/or second Covid-19 vaccination in 299 patients with CLL compared with healthy donors. 286 patients underwent extended interval (10–12 week) vaccination. 154 patients received the BNT162b2 mRNA vaccine and 145 patients received ChAdOx1. Blood samples were taken either by venepuncture or as dried blood spots on filter paper. Spike-specific antibody responses were detectable in 34% of patients with CLL after one vaccine (n = 267) compared to 94% in healthy donors with antibody titres 104-fold lower in the patient group. Antibody responses increased to 75% after second vaccine (n = 55), compared to 100% in healthy donors, although titres remained lower. Multivariate analysis showed that current treatment with BTK inhibitors or IgA deficiency were independently associated with failure to generate an antibody response after the second vaccine. This work supports the need for optimisation of vaccination strategy in patients with CLL including the potential utility of booster vaccines.

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Interferon activation status underlies higher antibody response to viral antigens in patients with systemic lupus erythematosus receiving no or light treatment

Rheumatology ◽

10.1093/rheumatology/keaa611 ◽

2020 ◽

Author(s):

Albin Björk ◽

Rui Da Silva Rodrigues ◽

Elina Richardsdotter Andersson ◽

Jorge I Ramírez Sepúlveda ◽

Johannes Mofors ◽

...

Keyword(s):

Antibody Response ◽

Specific Antibody ◽

Lupus Erythematosus ◽

Serum Proteins ◽

Light Treatment ◽

Antibody Responses ◽

Type I ◽

Specific Antibody Response ◽

Viral Antigens

Abstract Objectives Infections have been proposed as an environmental risk factor for autoimmune disease. Responses to microbial antigens may be studied in vivo during vaccination. We therefore followed patients with SLE and controls during split-virion influenza vaccination to quantify antibody responses against viral antigens and associated cellular and proteome parameters. Methods Blood samples and clinical data were collected from female patients with SLE with no or HCQ and/or low-dose prednisolone treatment (n = 29) and age- and sex-matched healthy controls (n = 17). Vaccine-specific antibody titres were measured by ELISA and IFN-induced gene expression in monocytes by quantitative PCR. Serum proteins were measured by proximity extension assay and disease-associated symptoms were followed by questionnaires. Results The vaccine-specific antibody response was significantly higher in patients compared with controls and titres of IgG targeting the viral proteins were higher in patients than controls at both 1 and 3 months after immunization. Clinical disease symptoms and autoantibody titres remained unchanged throughout the study. Notably, a positive pre-vaccination mRNA-based IFN score was associated with a significantly higher vaccine-specific antibody response and with a broader profile of autoantibody specificities. Screening of serum protein biomarkers revealed higher levels of IFN-regulated proteins in patients compared with controls and that levels of such proteins correlated with the vaccine-specific IgG response, with C-C motif chemokine ligand 3 exhibiting the strongest association. Conclusion Augmented antibody responses to viral antigens develop in patients with SLE on no or light treatment and associate with markers of type I IFN system activation at the RNA and protein levels.

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CpG Oligodeoxynucleotides Act as Adjuvants for Pneumococcal Polysaccharide-Protein Conjugate Vaccines and Enhance Antipolysaccharide Immunoglobulin G2a (IgG2a) and IgG3 Antibodies

Infection and Immunity ◽

10.1128/iai.68.3.1450-1456.2000 ◽

2000 ◽

Vol 68 (3) ◽

pp. 1450-1456 ◽

Cited By ~ 57

Author(s):

Rose S. Chu ◽

Tera McCool ◽

Neil S. Greenspan ◽

John R. Schreiber ◽

Clifford V. Harding

Keyword(s):

Antibody Response ◽

Specific Antibody ◽

Geometric Mean ◽

Fold Increase ◽

Antibody Responses ◽

Enzyme Linked Immunosorbent Assay ◽

Cpg Odn ◽

Conjugate Vaccines ◽

Specific Antibody Response ◽

Protein Conjugate

ABSTRACT Pneumococcal polysaccharide-protein conjugate vaccines elicit antipolysaccharide antibodies, but multiple doses are required to achieve protective antibody levels in children. In addition, the immunogenicity of experimental multivalent pneumococcal conjugate vaccines varies with different polysaccharide serotypes. One strategy to improve these vaccines is to incorporate an adjuvant to enhance their immunogenicity. Synthetic oligodeoxynucleotides containing unmethylated CpG motifs (CpG ODN) are adjuvants that promote T-cell and T-dependent antibody responses to protein antigens, but it has been unclear whether CpG ODN can enhance polysaccharide-specific antibody responses. The present studies demonstrate significant adjuvant activity of CpG ODN for antibody responses against Streptococcus pneumoniae polysaccharide types 19F and 6B induced by conjugates of 19F and 6B with the protein carrier CRM197. BALB/c ByJ mice were injected with 19F-CRM197 or 6B-CRM197with or without CpG ODN, and sera were tested for anti-19F or anti-6B antibodies by enzyme-linked immunosorbent assay. The polysaccharide-specific antibody response to 19F-CRM197alone was predominantly of the immunoglobulin G1 (IgG1) and IgM isotypes, but addition of CpG ODN markedly increased geometric mean titers of total anti-19F antibody (23-fold), anti-19F IgG2a (26-fold), and anti-19F IgG3 (>246-fold). The polysaccharide-specific antibody response to 6B-CRM197 alone consisted only of IgM, but addition of CpG ODN induced high titers of anti-6B IgG1 (>78-fold increase), anti-6B IgG2a (>54-fold increase), and anti-6B IgG3 (>3,162-fold increase). CpG ODN also increased anti-CRM197IgG2a and IgG3. Adjuvant effects were not observed with control non-CpG ODN. Thus, CpG ODN significantly enhance antipolysaccharide IgG responses (especially IgG2a and IgG3) induced by these glycoconjugate vaccines.

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The Immune Enhancement of Sodium Lauryl Sulfoacetate in Chickens

Veterinary Medicine International ◽

10.4061/2010/485060 ◽

2010 ◽

Vol 2010 ◽

pp. 1-5

Author(s):

DaRong Cheng ◽

ShanYuan Zhu ◽

HuaiChang Sun

Keyword(s):

T Cell ◽

Antibody Response ◽

Specific Antibody ◽

Mononuclear Cells ◽

Control Group ◽

Peripheral Blood Mononuclear ◽

Specific Antibody Response ◽

Cell Ratio

The purpose of this study is to investigate feasibility of sodium lauryl sulfoacetate (SLS) as an immunoadjuvant in chickens. After treating with 62.5, 125, 250, or 500 μg/mL SLS in vitro, lymphocyte proliferation assay of chicken peripheral blood mononuclear cells showed that theOD570values of all experimental groups, as well as Con A-stimulated group, were significantly higher than that of the untreated control group. After injection with 1.0, 2.0, or 4.0 mg/kg of SLS for 3 consecutive days, chickens were vaccinated with an attenuated vaccine againstNewcastle disease virus(NDV), and the immunoadjuvant effects of SLS were evaluated on the basis of immune organ index, antibody response, andCD4+/CD8+T-cell ratio. The results confirmed that SLS could enhance NDV-specific antibody response and increaseCD4+/CD8+T-cell ratio in vivo. Furthermore, SLS could improve NDV-specific antibody response in thiamphenicol-treated chickens. These data indicate that SLS not only can improve humoral immune response but also reverse the immunosuppressive effect of thiamphenicol in chickens.

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The effects of immunization with recombinant Sm14 (rSm14) in reducing worm burden and mortality of mice infected with Schistosoma mansoni

Revista da Sociedade Brasileira de Medicina Tropical ◽

10.1590/s0037-86822002000100003 ◽

2002 ◽

Vol 35 (1) ◽

pp. 11-17 ◽

Cited By ~ 6

Author(s):

Fábio Ribeiro ◽

Cristiane dos Santos Vieira ◽

Adriana Fernandes ◽

Neusa Araújo ◽

Naftale Katz

Keyword(s):

Antibody Response ◽

Schistosoma Mansoni ◽

Specific Antibody ◽

Post Infection ◽

Worm Burden ◽

Challenge Infection ◽

Control Group ◽

Significant Protection ◽

Lethal Challenge ◽

Specific Antibody Response

To investigate whether mice immunization with the recombinant form of a 14.7 KDa Schistosoma mansoni protein (rSm14) confers protection against a S. mansoni lethal challenge infection, rSm14-immunized mice were challenged with different cercarial burdens. A significant protection was detected in immunized mice challenged with 100 or 1,000 S. mansoni cercariae when compared with their controls (p< 0.004 and p< 0.01 respectively). Differently from previous report, none of the mice from the control group (not immunized and infected with 1000 cercariae) died before the 30th day post-infection. A direct correlation between the number of challenge cercariae and the precocity of mice death was found. IgM anti-rSm14 antibodies were significantly produced (p< 0.05) mainly in the groups of immunized mice infected with 500 or 1000 cercariae. IgG and IgA anti-rSm14 antibodies were not significantly detected. In Western immunoblots, all mice sera showed a specific antibody response with a 14.7 KDa antigen being reacted with particular intensity in sera from immunized mice. The results show that immunization with rSm14 reduced mice worm burden independently of the cercariae load of challenge infection. No correlation was found between serum antibodies and worm burden reduction. In relation to cercarial load and the rate and precocity of mice mortality a direct correlation was found.

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