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

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.

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

2022 ◽  
Vol 15 (1) ◽  
Author(s):  
Helen Parry ◽  
Graham McIlroy ◽  
Rachel Bruton ◽  
Sarah Damery ◽  
Grace Tyson ◽  
...  
Keyword(s):  
Antibody Response ◽  
Chronic Lymphocytic Leukaemia ◽  
Specific Antibody ◽  
Lymphocytic Leukaemia ◽  
Risk Groups ◽  
Antibody Responses ◽  
Clinical Feature ◽  
Control Group ◽  
Vaccine Platform ◽  
Specific Antibody Response

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.

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

Rheumatology ◽  
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.

scholarly journals The study of antibody responses to influenza neuraminidase using a lentiviral pseudotype based ELLA

2017 ◽  
Author(s):  
Fabrizio Biuso ◽  
George Carnell ◽  
Emanuele Montomoli ◽  
Nigel Temperton
Keyword(s):  
Antibody Response ◽  
Specific Antibody ◽  
Virus Entry ◽  
Antibody Responses ◽  
Surface Glycoprotein ◽  
Wild Type Virus ◽  
Target Cells ◽  
Type Virus ◽  
Wild Type ◽  
Reassortant Viruses

AbstractInfluenza pseudotypes represent an alternative to wild type virus for serological assays. To date, pseudotypes (PV) have predominantly been used as surrogates for wild type viruses in microneutralisation assays, where the surface glycoprotein of interest and a reporter gene (such as Luciferase) are used to assess if virus entry into target cells could be inhibited by serum antibodies. The influenza neuraminidase (NA) has the ability to bud and release new virions with or without the contribution of Haemagglutinin (HA). Influenza pseudotypes expressing NA alone, or with HA, were produced to evaluate the antibody response against NA using the enzyme-linked lectin assay (ELLA). The expression of an avian HA with human NAs has enabled the detection of specific antibody reponses against the human circulating subtypes of NA. Within this study a PV-based ELLA assay has been investigated with a pilot panel of sera prepared for an international CONSISE study. Preliminary results have confirmed that the assay is sensitive and could potentially represent a valid alternative to the classical ELLA assay, which requires the employment of reassortant viruses.

scholarly journals Antibody Responses After First and Second COVID-19 Vaccination in Patients With Chronic Lymphocytic Leukaemia

2021 ◽  
Author(s):  
Helen Marie Parry ◽  
Graham McIlroy ◽  
Rachel Bruton ◽  
Myah Ali ◽  
Christine Stephens ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukaemia ◽  
Lymphocytic Leukaemia ◽  
Antibody Responses

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

2000 ◽  
Vol 68 (3) ◽  
pp. 1450-1456 ◽  
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.

scholarly journals Novel, Chimpanzee Serotype 68-Based Adenoviral Vaccine Carrier for Induction of Antibodies to a Transgene Product

2002 ◽  
Vol 76 (6) ◽  
pp. 2667-2675 ◽  
Author(s):  
Zhiquan Xiang ◽  
Guangping Gao ◽  
Arturo Reyes-Sandoval ◽  
Christopher J. Cohen ◽  
Yan Li ◽  
...  
Keyword(s):  
Antibody Response ◽  
Rabies Virus ◽  
Specific Antibody ◽  
Lethal Dose ◽  
Antibody Responses ◽  
Distinct Advantage ◽  
Rabies Virus Glycoprotein ◽  
Virus Glycoprotein ◽  
Virus Specific Antibody ◽  
Vaccine Carrier

ABSTRACT An E1-deletion-containing adenoviral recombinant based on the chimpanzee serotype 68 (AdC68) was developed to express the rabies virus glycoprotein. Mice immunized with this construct (AdC68rab.gp) developed antibodies to rabies virus and remained resistant to challenge with an otherwise lethal dose of rabies virus. In naïve mice immunized intranasally, the rabies virus-specific antibody responses elicited by AdC68rab.gp were comparable with regard to both titers and isotype profiles to those induced by an adenoviral recombinant based on human serotype 5 (Adhu5) expressing the same transgene product. In contrast, subcutaneous immunization with the AdC68rab.gp vaccine resulted in markedly lower antibody responses to the rabies virus glycoprotein than the corresponding Adhu5 vaccine. Antibodies from AdC68rab.gp-immunized mice were strongly biased towards the immunoglobulin G2a isotype. The antibody response to the rabies virus glycoprotein presented by Adhu5rab.gp was severely compromised in animals preexposed to the homologous adenovirus. In contrast, the rabies virus-specific antibody response to the AdC68rab.gp vaccine was at most marginally affected by preexisting immunity to common human adenovirus serotypes, such as 2, 4, 5, 7, and 12. This novel vaccine carrier thus offers a distinct advantage over adenoviral vaccines based on common human serotypes.

scholarly journals Antibody signatures of asymptomatic Plasmodium falciparum malaria infections measured from dried blood spots

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Christine F. Markwalter ◽  
Myat Htut Nyunt ◽  
Zay Yar Han ◽  
Ricardo Henao ◽  
Aarti Jain ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Specific Antibody ◽  
Predictive Value ◽  
Dried Blood Spots ◽  
Protein Microarrays ◽  
Antibody Responses ◽  
Antibody Activity ◽  
Low Density ◽  
Blood Spots ◽  
Diagnostic Characteristics

Abstract Background Screening malaria-specific antibody responses on protein microarrays can help identify immune factors that mediate protection against malaria infection, disease, and transmission, as well as markers of past exposure to both malaria parasites and mosquito vectors. Most malaria protein microarray work has used serum as the sample matrix, requiring prompt laboratory processing and a continuous cold chain, thus limiting applications in remote locations. Dried blood spots (DBS) pose minimal biohazard, do not require immediate laboratory processing, and are stable at room temperature for transport, making them potentially superior alternatives to serum. The goals of this study were to assess the viability of DBS as a source for antibody profiling and to use DBS to identify serological signatures of low-density Plasmodium falciparum infections in malaria-endemic regions of Myanmar. Methods Matched DBS and serum samples from a cross-sectional study in Ingapu Township, Myanmar were probed on protein microarrays populated with P. falciparum antigen fragments. Signal and trends in both sample matrices were compared. A case-control study was then performed using banked DBS samples from malaria-endemic regions of Myanmar, and a regularized logistic regression model was used to identify antibody signatures of ultrasensitive PCR-positive P. falciparum infections. Results Approximately 30% of serum IgG activity was recovered from DBS. Despite this loss of antibody activity, antigen and population trends were well-matched between the two sample matrices. Responses to 18 protein fragments were associated with the odds of asymptomatic P. falciparum infection, albeit with modest diagnostic characteristics (sensitivity 58%, specificity 85%, negative predictive value 88%, and positive predictive value 52%). Conclusions Malaria-specific antibody responses can be reliably detected, quantified, and analysed from DBS, opening the door to serological studies in populations where serum collection, transport, and storage would otherwise be impossible. While test characteristics of antibody signatures were insufficient for individual diagnosis, serological testing may be useful for identifying exposure to asymptomatic, low-density malaria infections, particularly if sero-surveillance strategies target individuals with low previous exposure as sentinels for population exposure.

scholarly journals Changes in SARS-CoV-2 Spike versus Nucleoprotein Antibody Responses Impact the Estimates of Infections in Population-Based Seroprevalence Studies

2020 ◽  
Author(s):  
Craig Fenwick ◽  
Antony Croxatto ◽  
Alix T. Coste ◽  
Florence Pojer ◽  
Cyril André ◽  
...  
Keyword(s):  
General Population ◽  
Antibody Response ◽  
Specific Antibody ◽  
Post Infection ◽  
Acute Infection ◽  
Population Based ◽  
Antibody Responses ◽  
S Protein ◽  
N Protein ◽  
Protein Assays

SARS-CoV-2-specific antibody responses to the Spike (S) protein monomer, S protein native trimeric form or the nucleocapsid (N) proteins were evaluated in cohorts of individuals with acute infection (n=93) and in individuals enrolled in a post-infection seroprevalence population study (n=578) in Switzerland. Commercial assays specific for the S1 monomer, for the N protein and a newly developed Luminex assay using the S protein trimer were found to be equally sensitive in antibody detection in the acute infection phase samples. Interestingly, as compared to anti-S antibody responses, those against the N protein appear to wane in the post-infection cohort. Seroprevalence in a ‘positive patient contacts’ group (n=177) was underestimated by N protein assays by 10.9 to 32.2% and the ‘random selected’ general population group (n=311) was reduced up to 45% reduction relative to S protein assays. The overall reduction in seroprevalence targeting only anti-N antibodies for the total cohort ranged from 9.4 to 31%. Of note, the use of the S protein in its native trimer form was significantly more sensitive as compared to monomeric S proteins. These results indicate that the assessment of anti-S IgG antibody responses against the native trimeric S protein should be implemented to estimate SARS-CoV-2 infections in population-based seroprevalence studies. IMPORTANCE In the present study, we have determined SARS-CoV-2-specific antibody responses in sera of acute and post-infection phase subjects. Our results indicate that antibody responses against viral S and N proteins were equally sensitive in the acute phase of infection but that responses against N appear to wane in the post-infection phase while those against S protein persist over time. The most sensitive serological assay in both acute and post-infection phases used the native S protein trimer as binding antigen that has significantly greater conformational epitopes for antibody binding compared to the S1 monomer protein used in other assays. We believe that these results are extremely important in order to generate correct estimates of SARS-CoV-2 infections in the general population. Furthermore, the assessment of antibody responses against the trimeric S protein will be critical to evaluate the durability of the antibody response and for the characterization of a vaccine-induced antibody response.

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