Effect of the tumor-shed antigen CA125 on humoral immune responses of IgG1, IgG3, and IgM-type antibodies.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 15-15
Author(s):  
J Bradford Kline
Keyword(s):  
Ovarian Cancer ◽  
Immune Responses ◽  
Folate Receptor ◽  
Standard Of Care ◽  
Serum Levels ◽  
Serum Samples ◽  
Host Immune Responses ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Platinum Sensitive

15 Background: Human cancers employ a number of mechanisms to evade host immune responses. Here we report the effects of CA125 on suppressing humoral immune responses of naturally occurring and therapeutic antibodies (Abs). These data stem from prespecified subgroup analysis of a Ph3 trial testing farletuzumab, a monoclonal Ab (mAb) to folate receptor alpha, plus standard-of-care carboplatin-taxane (CT) chemotherapy in patients with recurrent platinum-sensitive ovarian cancer. Patients with low CA125 serum levels treated with farletuzumab plus CT demonstrated improvements in PFS (HR 0.49, p = 0.0028) and OS (HR 0.44, p = 0.0108) compared to placebo plus CT. Farletuzumab utilizes Ab-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) with the aim to kill target bound tumor cells. These functions were analyzed in patient samples to determine if CA125 negatively impacts mAb-mediated humoral responses. Methods: Molecular and cell based assays tested the effects of CA125 on humoral immune activity mediated by mAbs on ovarian cancer patient serum samples. Results: Here we show that CA125 inhibits ADCC and CDC by directly binding to a subset of mAbs and perturbing engagement with Fc-γ activating receptors CD16a and CD32a and the C1q complement initiating protein. The effects occur via CA125 binding to the mAb variable domain, which alters the structure of the CH2 motif leading to suppressed binding by CD16a/CD32a and C1q. The lack of inhibition by the high affinity CD64a Fc-γ receptor as well as lack of FcRn inhibition suggests a conformational change occurs within the CH2 motif that perturbs the binding of low affinity CD16a, CD32a and C1q proteins. The effect appears to involve a subset of Abs composed of IgG1, IgG3 and IgM isotypes. Conclusions: CA125 has an immunosuppressive effect on Ab-mediated humor immunity in a subset of tested Abs of varied isotypes including IgG1, IgG3, and IgM. The effects have implications in monitoring therapeutic mAbs that may be negatively affected by CA125 binding as well as potential implications for identifying patients who may be at risk for developing certain types of cancer, including ovarian.

scholarly journals Immunological and Microbiological Profiling of Cumulative Risk Score for Periodontitis

Diagnostics ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 560 ◽  
Author(s):  
Joonas Liukkonen ◽  
Ulvi K. Gürsoy ◽  
Eija Könönen ◽  
Ramin Akhi ◽  
Aino Salminen ◽  
...  
Keyword(s):  
Immune Responses ◽  
Risk Score ◽  
Cumulative Risk ◽  
Diagnostic Model ◽  
Serum Samples ◽  
Igg Antibody ◽  
Host Immune Responses ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Local Host

The cumulative risk score (CRS) is a mathematical salivary diagnostic model to define an individual’s risk of having periodontitis. In order to further validate this salivary biomarker, we investigated how periodontal bacteria, lipopolysaccharide (LPS), and systemic and local host immune responses relate to CRS. Subgingival plaque, saliva, and serum samples collected from 445 individuals were used in the analyses. Plaque levels of 28 microbial species, especially those of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Porphyromonas endodontalis, Prevotella intermedia, and Tannerella forsythia, and serum and salivary levels of IgA and IgG against these five species were determined. Additionally, LPS activity was measured. High CRS associated strongly with all IgA/IgG antibody and LPS levels in saliva, whereas in serum the associations were not that obvious. In the final logistic regression model, the best predictors of high CRS were saliva IgA burden against the five species (OR 7.04, 95% CI 2.25–22.0), IgG burden (3.79, 1.78–8.08), LPS (2.19, 1.38–3.47), and the sum of 17 subgingival Gram-negative species (6.19, 2.10–18.3). CRS is strongly associated with microbial biomarker species of periodontitis and salivary humoral immune responses against them.

Cellular and humoral immune responses to MUC1 mucin and tandem-repeat peptides in ovarian cancer patients and controls

1999 ◽  
Vol 48 (1) ◽  
pp. 47-55 ◽  
Author(s):  
F. G. M. Snijdewint ◽  
S. von Mensdorff-Pouilly ◽  
A. H. Karuntu-Wanamarta ◽  
A. A. Verstraeten ◽  
I. van Zanten-Przybysz ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Immune Responses ◽  
Cancer Patients ◽  
Tandem Repeat ◽  
Humoral Immune ◽  
Muc1 Mucin ◽  
Humoral Immune Responses

Analysis of Humoral Immune Responses in Chikungunya Virus (CHIKV)-Infected Patients and Individuals Vaccinated With a Candidate CHIKV Vaccine

2019 ◽  
Vol 221 (10) ◽  
pp. 1713-1723
Author(s):  
Lisa Henss ◽  
Constanze Yue ◽  
Christine Von Rhein ◽  
Roland Tschismarov ◽  
Lia Laura Lewis-Ximenez ◽  
...  
Keyword(s):  
Immune Responses ◽  
Chikungunya Virus ◽  
Cross Reactivity ◽  
Similar Extent ◽  
Serum Samples ◽  
Neutralization Activity ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Cross Neutralization ◽  
Binding Avidity

Abstract Background Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes severe flu-like symptoms. The acute symptoms disappear after 1 week, but chronic arthralgia can persist for years. In this study, humoral immune responses in CHIKV-infected patients and vaccinees were analyzed. Methods Alphavirus neutralization activity was analyzed with pseudotyped lentiviral vectors, and antibody epitope mapping was performed with a peptide array. Results The greatest CHIKV neutralization activity was observed 60–92 days after onset of symptoms. The amount of CHIKV-specific antibodies and their binding avidity and cross-reactivity with other alphaviruses increased over time. Chikungunya virus and o’nyong-nyong virus (ONNV) were both neutralized to a similar extent. Linear antibody binding epitopes were mainly found in E2 domain B and the acid-sensitive regions (ASRs). In addition, serum samples from healthy volunteers vaccinated with a measles-vectored chikungunya vaccine candidate, MV-CHIK, were analyzed. Neutralization activity in the samples from the vaccine cohort was 2- to 6-fold lower than in samples from CHIKV-infected patients. In contrast to infection, vaccination only induced cross-neutralization with ONNV, and the E2 ASR1 was the major antibody target. Conclusions These data could assist vaccine design and enable the identification of correlates of protection necessary for vaccine efficacy.

Effect of CA125/MUC16 on complement-dependent cytotoxicity (CDC) of farletuzumab and other CDC-mediating antibodies via inhibition of antibody-C1q binding.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23082-e23082 ◽  
Author(s):  
J Bradford Kline ◽  
Shawn Fernando ◽  
Stephen Harley ◽  
Luigi Grasso ◽  
Nicholas C Nicolaides
Keyword(s):  
Immune Responses ◽  
Cell Lines ◽  
Folate Receptor ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Recurrent Ovarian Cancer ◽  
Cellular Cytotoxicity ◽  
Host Immune Responses ◽  
Investigational Agent ◽  
Functional Assays

e23082 Background: Human cancers employ a number of mechanisms to evade host immune responses. Here we report the effects of the tumor-shed antigen CA125 on suppressing complement-dependent cellular cytotoxicity (CDC). This finding relates to a prespecified subgroup analysis of an 1100 patient Ph3 clinical trial testing the investigational agent farletuzumab, a monoclonal antibody (mAb) to folate receptor alpha, plus standard-of-care chemotherapy in patients with recurrent ovarian cancer. In this study, patients with low levels of CA125 (no greater than 3X the upper limit of normal) treated with farletuzumab compared to placebo demonstrated improvements in both progression free survival (HR 0.49, p = 0.0028) and overall survival (HR 0.44, p = 0.0108). Farletuzumab’s pharmacologic activity is mediated in part through antibody dependent cellular cytotoxicity (ADCC) and CDC. Here we show that CA125 inhibits IgG1- and IgM-mediated CDC by suppressing antibody interaction with the C1q complement-initiating protein. Methods: Functional assays employing cell lines expressing antibody-specific antigens were used to measure CDC activity. CA125 isolates from various patients and cell lines were used to monitor CA125 effects on complement function. ELISA assays were used to measure the effects of CA125 inhibition on C1q-antibody interaction. Results: Functional assays showed that CA125 suppressed antibody-mediated CDC in a dose dependent fashion. Molecular studies revealed that this suppression is caused by CA125 binding to antibody, leading to suppression of antibody-C1q interaction. Conclusions: Here we demonstrate that CA125 can elicit immunosuppression by perturbing the interaction of tumor targeting antibodies and the C1q complement-initiating protein. This effect is through a direct binding of CA125 to antibody. These findings provide new insights into the potential biological mechanisms by which tumors produce tumor shed antigens like CA125 to suppress host immune responses such as CDC. This finding has important clinical applications for the development of therapeutics utilizing complement-mediated mechanisms.

scholarly journals Antibody Responses to SARS-CoV-2 Antigens in Humans and Animals

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 684
Author(s):  
Hyunsuh Kim ◽  
Patrick Seiler ◽  
Jeremy C. Jones ◽  
Granger Ridout ◽  
Kristi P. Camp ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cross Reactivity ◽  
Serum Samples ◽  
Public Health Response ◽  
The Public ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Health Response ◽  
Seroepidemiologic Studies ◽  
Human Coronaviruses

To optimize the public health response to coronavirus disease 2019 (COVID-19), we must first understand the antibody response to individual proteins on the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and the antibody’s cross reactivity to other coronaviruses. Using a panel of 37 convalescent COVID-19 human serum samples, we showed that the magnitude and specificity of responses varied across individuals, independent of their reactivity to seasonal human coronaviruses (HCoVs). These data suggest that COVID-19 vaccines will elicit primary humoral immune responses in naïve individuals and variable responses in those previously exposed to SARS-CoV-2. Unlike the limited cross-coronavirus reactivities in humans, serum samples from 96 dogs and 10 cats showed SARS-CoV-2 protein-specific responses focused on non–S1 proteins. The correlation of this response with those to other coronaviruses suggests that the antibodies are cross-reactive and generated to endemic viruses within these hosts, which must be considered in seroepidemiologic studies. We conclude that substantial variation in antibody generation against coronavirus proteins will influence interpretations of serologic data in the clinical and veterinary settings.

scholarly journals Analysis of Humoral Immune Responses in Chikungunya Virus (CHIKV)-Infected Patients and Individuals Vaccinated with a Candidate CHIKV Vaccine

Proceedings ◽  
2020 ◽  
Vol 50 (1) ◽  
pp. 95
Author(s):  
Lisa Henss ◽  
Constanze Yue ◽  
Christine von Rhein ◽  
Roland Tschismarov ◽  
Lia-Laura Lewis-Ximenez ◽  
...  
Keyword(s):  
Immune Responses ◽  
Chikungunya Virus ◽  
Cross Reactivity ◽  
Similar Extent ◽  
Serum Samples ◽  
Neutralization Activity ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Cross Neutralization ◽  
Binding Avidity

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes severe flu-like symptoms. The acute symptoms disappear after one week, but chronic arthralgia can persist for years. Here, humoral immune responses in CHIKV-infected patients and vaccinees were analyzed. Alphavirus neutralization activity was analyzed with pseudotyped lentiviral vectors and antibody epitope mapping was performed with a peptide array. The greatest CHIKV neutralization activity was observed 60–92 days after onset of symptoms. The amount of CHIKV-specific antibodies, their binding avidity, and cross-reactivity with other alphaviruses increased over time. CHIKV and o’nyong-nyong virus (ONNV) were both neutralized to a similar extent. Linear antibody binding epitopes were mainly found in E2 domain B and the acid-sensitive regions (ASRs). In addition, serum samples from healthy volunteers vaccinated with a measles-vectored Chikungunya vaccine candidate, MV-CHIK, were analyzed. Neutralization activity in the samples from the vaccine cohort was lower than in samples from CHIKV-infected patients. In contrast to infection, vaccination induced cross-neutralization with ONNV and the E2 ASR1 was the major antibody target. These data could assist vaccine design and enable the identification of correlates of protection necessary for vaccine efficacy.

scholarly journals INFLUENCE OF MYCOTOXINS ON IMMUNE RESPONSES AGAINST SALMONELLA TYPHIMURIUM INFECTION OF BROILER CHICKENS

2020 ◽  
Vol 51 (6) ◽  
pp. 1716-1725
Author(s):  
Jawad & ALwan
Keyword(s):  
Immune Responses ◽  
Broiler Chickens ◽  
Serum Levels ◽  
Phagocytic Index ◽  
High Dose ◽  
Negative Group ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Sterile Normal Saline ◽  
Antibody Titers

Forty broiler chickens, One - day old were randomly divided into four equal groups:  1st group was immunized with 0.5 ml of whole sonicated salmonella antigens (WSSAgs), protein concentration 1.89 mg/ml. Two dose  two weeks intervals, S/C at 7 days old  and  the  chicks  fed   contaminated diet with  mycotoxins for 7 week,   2nd group was immunized with WSSAgs only and treated  as  1st group,  3rd group fed diet contaminated with  mycotoxins  and 4th group was fed  normal diets and served as control negative group, At 30 days, skin test, phagocytic index and serum levels of antibody titers were done, then 1st ,2nd and 3rd groups were inoculated with  high dose of  virulent S.typhimurium , (1ml containing   1  10 12  CFU/ml ), I/V, and  4th group was inoculated I/V,1ml  sterile normal saline and served as control negative group , all chicks were sacrificed at  3 weeks post infection, it was recorded that mycotoxin suppress the  cellular and  humoral immune responses , phagocytic activity ,in addition to high mortality rate were found in  chicks fed contaminated diet with  and without immunization.

scholarly journals Immunological Fingerprinting Method for Differentiation of Serum Samples in Research-Oriented Biobanks

2010 ◽  
Vol 17 (5) ◽  
pp. 735-740 ◽  
Author(s):  
Katy Beaumont ◽  
Fotini Betsou
Keyword(s):  
Quality Control ◽  
Immune Responses ◽  
Serum Sample ◽  
Control Method ◽  
Serum Samples ◽  
Blood Specimen ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Quality Control Method ◽  
Fingerprinting Method

ABSTRACT An immunoenzymatic serum fingerprinting method was developed to establish a serum sample fingerprint based on IgG titers obtained with three different antigens. Three widely expressed antigens were selected for their capacity to induce long-lasting humoral immune responses. This fingerprinting method may be used to differentiate between two serum samples and to determine whether they come from the same primary blood specimen. The method showed a specificity of 99.5%. This method is suitable as a quality control method for biobanked serum samples.

scholarly journals Humoral Immune Response after Primary Rubella Virus Infection and after Vaccination

2007 ◽  
Vol 14 (5) ◽  
pp. 644-647 ◽  
Author(s):  
C. Vauloup-Fellous ◽  
L. Grangeot-Keros
Keyword(s):  
Immune Response ◽  
Virus Infection ◽  
Immune Responses ◽  
Humoral Immune Response ◽  
Rubella Virus ◽  
Primary Infection ◽  
Serum Samples ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Rubella Virus Infection

ABSTRACT We measured rubella virus immunoglobulin G (IgG) and IgM levels, as well as IgG avidity indexes, in serum samples taken before or after 6 months either after infection or after vaccination. The results obtained indicate that humoral immune responses are different after primary infection and after vaccination. This may have important consequences on the serological diagnosis of rubella virus infection.

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