scholarly journals Dynamics of the Magnitude, Breadth and Depth of the Antibody Response at Epitope Level Following Dengue Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Francesca Falconi-Agapito ◽  
Karen Kerkhof ◽  
Xiomara Merino ◽  
Johan Michiels ◽  
Marjan Van Esbroeck ◽  
...  

Dengue is a major public health problem in tropical and sub-tropical regions worldwide. Since the Zika epidemic and the increased co-circulation of other arboviruses, the serology-based diagnosis of dengue has become more problematic due to the high antigenic resemblance, especially among the flavivirus family. Therefore, a more comprehensive understanding of the diversity, specificity and temporal evolution of the antibody response following dengue infection is needed. In order to close this knowledge gap, we used a high-density peptide microarray of 9,072 linear peptides covering the entire proteome diversity of dengue, Zika, yellow fever and chikungunya viruses. The IgM and IgG antibody responses were measured against the designed microarray in symptomatic dengue infected individuals from an arbovirus endemic area in Peru and in overseas travelers returning to Belgium, as representatives of multiple-exposed and primary infections, respectively. Serum samples were collected longitudinally across four time points over the period of six months in Peru and over two time points in travelers. We show that epitopes eliciting the strongest flavivirus cross-reactive antibodies, in both primary and secondary infections were concentrated in the capsid, E, NS1, NS3 and NS5 proteins. The IgG antibody responses against NS1 and NS3 followed a rise-and-fall pattern, with peak titers between two to four weeks after onset of illness. The response to the E and NS5 proteins increased rapidly in the acute phase and was maintained at stable levels until at least 6 months after illness. A more scattered IgM antibody reactivity across the viral proteome was observed in the acute phase of the disease and that persisted through the 6-month window. The magnitude, breadth (i.e. number of unique epitopes targeted) and depth (i.e. number of epitope variants recognized) of the IgG response was higher in secondary infections compared to primary infections. For IgM antibodies, the magnitude of the response was higher in primary infected individuals whereas the breadth and depth of the response was lower in this group compared with the endemic subjects. Finally, through this arboviral proteome-wide epitope mapping, we were able to identify IgM and IgG dengue-specific epitopes which can be useful serological markers for dengue diagnosis and serostatus determination.

2020 ◽  
Author(s):  
Girish Chandra Dash ◽  
Debaprasad Parai ◽  
Hari Ram Choudhary ◽  
Annalisha Peter ◽  
Usha Kiran Rout ◽  
...  

AbstractThe SARS-CoV-2 antibody responses remain poorly understood and the clinical utility of serological testing is still unclear. As it is thought to confer some degree of immunity, this study is carried out to know the relationship between demographics and ct value of confirmed rt-PCR patients. A total of 384 serum samples were collected between 4-6 weeks after confirmed SARS-CoV-2 infection. IgG positivity was found to be 80.2% (95% CI, 76.2 – 84.2). The IgG positivity increased with the decrease in the ct value, with highest of 87.6% positivity in individuals with <20 ct value. The mean (± SD) ct value of IgG positives and og IgG negatives was 23.34 (± 6.09) and 26.72 (± 7.031) respectively. There was no significant difference found between the demographic characteristics such as age, sex, symptoms and antibody response. The current study is first of its kind wherein we have assessed the correlation of ct of RT-PCR with development of IgG against SARS-CoV-2. Our study showed that although Ct value might not have any relation with severity of the diseases but is associated with the antibody response among the SARS-CoV-2 infected individual.


2021 ◽  
Vol 3 (10) ◽  
Author(s):  
Girish Chandra Dash ◽  
Debaprasad Parai ◽  
Hari Ram Choudhary ◽  
Annalisha Peter ◽  
Usha Kiran Rout ◽  
...  

Introduction. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody responses remain poorly understood and the clinical utility of serological testing is still unclear. Aim. To understand the relationship between the antibody response to SARS-CoV-2 infection and the demographics and cycle threshold (C t) values of confirmed RT-PCR patients. Methodology. A total of 384 serum samples were collected from individuals between 4–6 weeks after confirmed SARS-CoV-2 infection and tested for the development of immunoglobulin class G (IgG) against SARS-CoV-2. The C t values, age, gender and symptoms of the patients were correlated with the development of antibodies. Results. IgG positivity was found to be 80.2 % (95 % CI, 76.2–84.2). Positivity increased with a decrease in the C t value, with the highest (87.6 %) positivity observed in individuals with C t values <20. The mean (±sd) C t values for IgG positives and negatives were 23.34 (±6.09) and 26.72 (±7.031), respectively. No significant difference was found for demographic characteristics such as age and sex and symptoms and antibody response. The current study is the first of its kind wherein we have assessed the correlation of the RT-PCR C t with the development of IgG against SARS-CoV-2. Conclusion. Although C t values might not have any relation with the development of symptoms, they are associated with the antibody response among SARS-CoV-2-infected individuals.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Kosuke Miyauchi ◽  
Yu Adachi ◽  
Keisuke Tonouchi ◽  
Taiki Yajima ◽  
Yasuyo Harada ◽  
...  

AbstractInfluenza viruses are a major public health problem. Vaccines are the best available countermeasure to induce effective immunity against infection with seasonal influenza viruses; however, the breadth of antibody responses in infection versus vaccination is quite different. Here, we show that nasal infection controls two sequential processes to induce neutralizing IgG antibodies recognizing the hemagglutinin (HA) of heterotypic strains. The first is viral replication in the lung, which facilitates exposure of shared epitopes that are otherwise hidden from the immune system. The second process is the germinal center (GC) response, in particular, IL-4 derived from follicular helper T cells has an essential role in the expansion of rare GC-B cells recognizing the shared epitopes. Therefore, the combination of exposure of the shared epitopes and efficient proliferation of GC-B cells is critical for generating broadly-protective antibodies. These observations provide insight into mechanisms promoting broad protection from virus infection.


2009 ◽  
Vol 77 (5) ◽  
pp. 1976-1980 ◽  
Author(s):  
Leen Moens ◽  
Axel Jeurissen ◽  
Stefan Nierkens ◽  
Louis Boon ◽  
Luc Van Kaer ◽  
...  

ABSTRACT Streptococcus pneumoniae is a bacterial microorganism that frequently causes serious infection, particularly in children and the elderly. Protection against infection with S. pneumoniae is based mainly on the generation of antibodies to the pneumococcal capsular polysaccharides (caps-PS), but the mechanisms responsible for the generation of anticapsular antibodies remain incompletely understood. The aim of the present study was to evaluate the role of CD1-restricted T cells in the antibody response to caps-PS. When immunized with Pneumo23, wild-type mice and CD1 knockout mice on BALB/c and C57BL/6 backgrounds generated immunoglobulin M (IgM) and IgG antibody responses to soluble caps-PS that were comparable. Similar results were obtained after immunization with heat-inactivated S. pneumoniae. The IgM and IgG antibody response of wild-type mice to Pneumo23 was not affected by an antagonizing monoclonal anti-CD1 antibody treatment. In summary, our data provide evidence that the antibody response to caps-PS is generated independently of CD1 expression.


2005 ◽  
Vol 12 (2) ◽  
pp. 273-279 ◽  
Author(s):  
J. Xu ◽  
P. Dennehy ◽  
H. Keyserling ◽  
L. E. Westerman ◽  
Y. Wang ◽  
...  

ABSTRACT We examined sera from 42 patients 1 to 30 months of age for rotavirus immunoglobulin M (IgM), IgA, IgG, and IgG subclasses and sought to determine if serum antibody could serve as a reliable marker for prediction of disease severity. Infants in the first few months of life usually had high maternal IgG titers and, when they were infected with rotavirus, had low IgM titers or no IgM in acute-phase sera and poor seroconversions 3 weeks later, suggesting that maternal antibodies had inhibited viral replication and antibody responses. All patients ≥6 months of age had IgM in acute-phase sera, indicating that IgM is a good marker for acute rotavirus infection. IgG was the best overall predictor of an infection, as the convalescent-phase sera of 81% of the patients had a fourfold rise in the IgG titer. IgA titers in convalescent-phase sera and conversion rates were higher among patients ≥12 months of age than among children younger than 12 months. IgG1 was the predominant subclass detected in the acute-phase sera of some children and in all 28 convalescent-phase serum samples examined. Patients with preexisting acute-phase IgG titers of ≥100 or ≥200 had diarrhea that was less severe or of a shorter duration. These results indicate that serum IgG is the most reliable marker for seroconversion and is a consistent proxy for protection against severe disease.


2006 ◽  
Vol 13 (1) ◽  
pp. 123-131 ◽  
Author(s):  
Jeffrey W. Priest ◽  
Caryn Bern ◽  
Lihua Xiao ◽  
Jacquelin M. Roberts ◽  
James P. Kwon ◽  
...  

ABSTRACT Cryptosporidium species are ubiquitous in the environment and are frequently detected in the stools of children who live where sanitation conditions are poor. To better characterize the immune response to these parasites, we monitored immunoglobulin G (IgG) antibody levels in a cohort of children from Lima, Peru. Two new enzyme-linked immunosorbent assays based on the C. parvum (bovine, subtype IIa) Iowa strain 17-kDa and 27-kDa antigens were used to measure IgG antibody levels in longitudinal serum samples. Antibody responses were detected during infections with C. parvum, C. felis, and C. meleagridis and with four different subtypes of C. hominis. We also noted that the magnitude of the antibody response was related to the number of previous infections and that older children generally had higher levels of antibodies to the two C. parvum antigens. Antibody responses were not associated with infections with either Cyclospora sp. or Giardia sp. We believe the antibody assays will be important tools for monitoring the success of future public health interventions.


2004 ◽  
Vol 10 (4) ◽  
pp. 397-398 ◽  
Author(s):  
Viroj Wiwanitkit

Dengue infection is a major public health problem, affecting the general population in Southeast Asia. Hematologic aberrations in dengue infection include atypical lymphocytosis, coagulopathy, and predominant thrombocytopenia. Bleeding and other presentations in 30 Thai patients with dengue infection during an endemic season (2003) are presented. A review of the clinical presentation of these patients was performed. All had fever as a chief complaint. The three most common complaints were fever (100%), vomiting (90%), and cough (90%), respectively. Concerning bleeding, only eight cases (26.6%) had signs of bleeding. Those manifestations included petechiae (seven cases, 23.3%) and melena (one case, 3.3%). Skin bleeding (petechiae) due to thrombocytopenia is the most common bleeding manifestation in dengue infection. However, physicians should not overlook bleeding from other less common sites such as the gastrointestinal tract and genitourinary tract.


2020 ◽  
Vol 12 (3) ◽  
pp. 51-60
Author(s):  
Yudianto Budi Saroyo ◽  
Ali Sungkar ◽  
Rima Irwinda ◽  
Raymond Surya

Introduction: Dengue fever is a major public health problem in tropical and subtropical areas. There are not many studies concerning the complications of dengue fever in pregnancy. We present four serial cases of dengue fever in pregnancy. Case illustration: Three of four cases were delivered by caesarean section; two of them died during post-caesarean care. All cases had the lowest platelet level below 50,000/µL and were given platelet transfusion during and after delivery; they also showed abnormal liver function tests. For foetal outcome, none tested positive for dengue. Discussion: Complication of dengue infection depends on a combination of host and viral virulence. Regardless of prophylactic platelet transfusion, some studies revealed clinical bleeding in patients with dengue infection due to an intricate effect on the haemostatic system. The adverse foetal outcome may contribute because of placental circulation caused by endothelial damage with increased vascular permeability leading to plasma leakage. There is no national guideline for dengue fever in pregnancy. Conclusions: The management of dengue fever in pregnancy at the tertiary hospital is still suboptimal. Dengue fever around peripartum presents a higher risk of morbidity and mortality for the mother and therefore needs a multidiscipline team approach.


1974 ◽  
Vol 140 (1) ◽  
pp. 239-252 ◽  
Author(s):  
Tomio Tada ◽  
Toshitada Takemori

Passively transferred thymocytes and spleen cells from donors primed with keyhole limpet hemocyanin (KLH) exerted differential suppressive effect on IgM and IgG antibody responses of syngeneic recipients immunized with DNP-KLH depending primarily on the time when KLH-primed cells were transferred. This was demonstrated by the decrease in the numbers of DNP-specific direct and indirect PFC in the spleen of the recipients given KLH-primed cells at different times during primary and secondary immunization. Whereas the cell transfer simultaneously with or 2 days after the primary immunization produced only slight suppression of the peak IgM antibody response, it caused profound suppression of late IgM and IgG antibody responses. By contrast, the cell transfer 3 days after the immunization produced immediate suppression of the ongoing IgM antibody response resulting in its earlier termination, while being unable to prevent the induction of IgG antibody response. KLH-primed cells could moderately suppress the secondary anti-DNP antibody response, in which IgG antibody response was found to be slightly more sensitive than IgM antibody response to the suppressive influence of KLH-primed cells. The suppressive effect of the KLH-primed spleen cells was completely eliminated by the in vitro treatment of the cells with anti-θ and C before cell transfer, indicating that cells responsible for the suppression are, in fact, T cells. The suppression of DNP-specific antibody response by KLH-primed T cells was achieved only if the recipients were immunized with DNP-KLH but not with DNP-heterologous carrier, suggesting that direct interaction between T and B cells is necessary for the suppression of the antibody response. It is concluded that susceptibility of B cells to the specific suppressive influence of T cells is inherently different depending on the differentiation stage of B cells and on the immunoglobulin class they are destined to produce.


2010 ◽  
Vol 18 (3) ◽  
pp. 380-386 ◽  
Author(s):  
Kristina Crothers ◽  
Kieran R. Daly ◽  
David Rimland ◽  
Matthew Bidwell Goetz ◽  
Cynthia L. Gibert ◽  
...  

ABSTRACTSerologic studies can provide important insights into the epidemiology and transmission ofPneumocystis jirovecii. Exposure toP. jiroveciican be assessed by serum antibody responses to recombinant antigens from the major surface glycoprotein (MsgC), although factors that influence the magnitude of the antibody response are incompletely understood. We determined the magnitudes of antibody responses toP. jiroveciiin comparison to adenovirus and respiratory syncytial virus (RSV) in HIV-infected and uninfected patients and identified predictors associated with the magnitude of the response. We performed a cross-sectional analysis using serum samples and data from 153 HIV-positive and 92 HIV-negative subjects enrolled in a feasibility study of the Veterans Aging Cohort 5 Site Study (VACS 5). Antibodies were measured using an enzyme-linked immunosorbent assay (ELISA). Independent predictors of antibody responses were determined using multivariate Tobit regression models. The results showed that serum antibody responses toP. jiroveciiMsgC fragments were significantly and independently decreased in current smokers. Antibodies toP. jiroveciialso tended to be lower with chronic obstructive pulmonary disease (COPD), hazardous alcohol use, injection drug use, and HIV infection, although these results were not statistically significant. These results were specific toP. jiroveciiand did not correlate with adenovirus. Antibody responses to RSV were in the inverse direction. Thus, current smoking was independently associated with decreasedP. jiroveciiantibody responses. Whether smoking exerts an immunosuppressive effect that affects theP. jiroveciiantibody response, colonization, or subsequent risk for disease is unclear; prospective, longitudinal studies are needed to evaluate these findings further.


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