Antibody Responses against Enterovirus Proteases are Potential Markers for an Acute Infection

Background: Enteroviruses are a group of common non-enveloped RNA viruses that cause symptoms ranging from mild respiratory infections to paralysis. Due to the abundance of enterovirus infections it is hard to distinguish between on-going and previous infections using immunological assays unless the IgM fraction is studied. Methods: In this study we show using Indirect ELISA and capture IgM ELISA that an IgG antibody response against the nonstructural enteroviral proteins 2A and 3C can be used to distinguish between IgM positive (n = 22) and IgM negative (n = 20) human patients with 83% accuracy and a diagnostic odds ratio of 30. Using a mouse model, we establish that the antibody response to the proteases is short-lived compared to the antibody response to the structural proteins in. As such, the protease antibody response serves as a potential marker for an acute infection. Conclusions: Antibody responses against enterovirus proteases are shorter-lived than against structural proteins and can differentiate between IgM positive and negative patients, and therefore they are a potential marker for acute infections.

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Generation of Antibody Responses to Pneumococcal Capsular Polysaccharides Is Independent of CD1 Expression in Mice

Infection and Immunity ◽

10.1128/iai.01091-08 ◽

2009 ◽

Vol 77 (5) ◽

pp. 1976-1980 ◽

Cited By ~ 4

Author(s):

Leen Moens ◽

Axel Jeurissen ◽

Stefan Nierkens ◽

Louis Boon ◽

Luc Van Kaer ◽

...

Keyword(s):

Antibody Response ◽

The Elderly ◽

Immunoglobulin M ◽

Antibody Responses ◽

Capsular Polysaccharides ◽

Wild Type ◽

Igg Antibody ◽

Antibody Treatment ◽

Serious Infection ◽

Protection Against Infection

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.

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SELECTIVE ROLES OF THYMUS-DERIVED LYMPHOCYTES IN THE ANTIBODY RESPONSE

Journal of Experimental Medicine ◽

10.1084/jem.140.1.239 ◽

1974 ◽

Vol 140 (1) ◽

pp. 239-252 ◽

Cited By ~ 67

Author(s):

Tomio Tada ◽

Toshitada Takemori

Keyword(s):

T Cells ◽

B Cells ◽

Antibody Response ◽

Suppressive Effect ◽

Antibody Responses ◽

Cell Transfer ◽

Spleen Cells ◽

Igg Antibody ◽

Igm Antibody

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.

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SARS-CoV-2 IgG antibody responses in rt-PCR positive cases: first report from India

10.1101/2020.11.13.20229716 ◽

2020 ◽

Author(s):

Girish Chandra Dash ◽

Debaprasad Parai ◽

Hari Ram Choudhary ◽

Annalisha Peter ◽

Usha Kiran Rout ◽

...

Keyword(s):

Antibody Response ◽

Infected Individual ◽

Antibody Responses ◽

Rt Pcr ◽

Serum Samples ◽

Igg Antibody ◽

Ct Value ◽

Significant Difference ◽

The Mean ◽

The Relationship

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.

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Impact of Treatment Regimens on Antibody Response to the SARS-CoV-2 Coronavirus

Frontiers in Immunology ◽

10.3389/fimmu.2021.580147 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yufeng Shang ◽

Tao Liu ◽

Jingfeng Li ◽

Natasha Mupeta Kaweme ◽

Xinghuan Wang ◽

...

Keyword(s):

Critical Illness ◽

Antibody Response ◽

Multivariable Analysis ◽

Antibody Test ◽

Antibody Responses ◽

Systematic Evaluation ◽

Igg Antibody ◽

Treatment Regimens ◽

Asymptomatic Patients ◽

The Impact

The coronavirus disease 2019 (COVID-19) is widely spread and remains a global pandemic. Limited evidence on the systematic evaluation of the impact of treatment regimens on antibody responses exists. Our study aimed to analyze the role of antibody response on prognosis and determine factors influencing the IgG antibodies’ seroconversion. A total of 1,111 patients with mild to moderate COVID-19 symptoms admitted to Leishenshan Hospital in Wuhan were retrospectively analyzed. A serologic SARS-CoV-2 IgM/IgG antibody test was performed on all the patients 21 days after the onset of symptoms. Patient clinical characteristics were compared. In the study, 42 patients progressed to critical illness, with 6 mortalities reported while 1,069 patients reported mild to moderate disease. Advanced age (P = 0.028), gasping (P < 0.001), dyspnea (P = 0.024), and IgG negativity (P = 0.006) were associated with progression to critical illness. The mortality rate in critically ill patients with IgG antibody was 6.45% (95% CI 1.12–22.84%) and 36.36% (95% CI 12.36–68.38%) in patients with no IgG antibody (P = 0.003). Symptomatic patients were more likely to develop IgG antibody responses than asymptomatic patients. Using univariable analysis, fever (P < 0.001), gasping (P = 0.048), cancer (P < 0.001), cephalosporin (P = 0.015), and chloroquine/hydroxychloroquine (P = 0.021) were associated with IgG response. In the multivariable analysis, fever, cancer, cephalosporins, and chloroquine/hydroxychloroquine correlated independently with IgG response. We determined that the absence of SARS-CoV-2 antibody IgG in the convalescent stage had a specific predictive role in critical illness progression. Importantly, risk factors affecting seropositivity were identified, and the effect of antimalarial drugs on antibody response was determined.

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Reactivity of Porcine Epidemic Diarrhea Virus Structural Proteins to Antibodies against Porcine Enteric Coronaviruses: Diagnostic Implications

Journal of Clinical Microbiology ◽

10.1128/jcm.02507-16 ◽

2017 ◽

Vol 55 (5) ◽

pp. 1426-1436 ◽

Cited By ~ 26

Author(s):

Luis Gabriel Gimenez-Lirola ◽

Jianqiang Zhang ◽

Jose Antonio Carrillo-Avila ◽

Qi Chen ◽

Ronaldo Magtoto ◽

...

Keyword(s):

Antibody Response ◽

Porcine Epidemic Diarrhea Virus ◽

Herd Immunity ◽

Cross Reactivity ◽

Structural Proteins ◽

Transmissible Gastroenteritis Virus ◽

Serum Samples ◽

Igg Antibody ◽

Diarrhea Virus ◽

Porcine Epidemic Diarrhea

ABSTRACTThe development of porcine epidemic diarrhea virus (PEDV) antibody-based assays is important for detecting infected animals, confirming previous virus exposure, and monitoring sow herd immunity. However, the potential cross-reactivity among porcine coronaviruses is a major concern for the development of pathogen-specific assays. In this study, we used serum samples (n= 792) from pigs of precisely known infection status and a multiplex fluorescent microbead-based immunoassay and/or enzyme-linked immunoassay platform to characterize the antibody response to PEDV whole-virus (WV) particles and recombinant polypeptides derived from the four PEDV structural proteins, i.e., spike (S), nucleocapsid (N), membrane (M), and envelope (E). Antibody assay cutoff values were selected to provide 100% diagnostic specificity for each target. The earliest IgG antibody response, mainly directed against S1 polypeptides, was observed at days 7 to 10 postinfection. With the exception of nonreactive protein E, we observed similar antibody ontogenies and patterns of seroconversion for S1, N, M, and WV antigens. Recombinant S1 provided the best diagnostic sensitivity, regardless of the PEDV strain, with no cross-reactivity detected against transmissible gastroenteritis virus (TGEV), porcine respiratory coronavirus (PRCV), or porcine deltacoronavirus (PDCoV) pig antisera. The WV particles showed some cross-reactivity to TGEV Miller and TGEV Purdue antisera, while N protein presented some cross-reactivity to TGEV Miller. The M protein was highly cross-reactive to TGEV and PRCV antisera. Differences in the antibody responses to specific PEDV structural proteins have important implications in the development and performance of antibody assays for the diagnosis of PEDV enteric disease.

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Detection of Anti-SARS-CoV-2-S2 IgG Is More Sensitive Than Anti-RBD IgG in Identifying Asymptomatic COVID-19 Patients

Frontiers in Immunology ◽

10.3389/fimmu.2021.724763 ◽

2021 ◽

Vol 12 ◽

Author(s):

Baolin Liao ◽

Zhao Chen ◽

Peiyan Zheng ◽

Linghua Li ◽

Jianfen Zhuo ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Early Time ◽

Antibody Responses ◽

Structural Proteins ◽

Antibody Detection ◽

Igg Antibody ◽

Detection Scheme ◽

Asymptomatic Patients ◽

Asymptomatic Infections ◽

And Control

Characterizing the serologic features of asymptomatic SARS-CoV-2 infection is imperative to improve diagnostics and control of SARS-CoV-2 transmission. In this study, we evaluated the antibody profiles in 272 plasma samples collected from 59 COVID-19 patients, consisting of 18 asymptomatic patients, 33 mildly ill patients and 8 severely ill patients. We measured the IgG against five viral structural proteins, different isotypes of immunoglobulins against the Receptor Binding Domain (RBD) protein, and neutralizing antibodies. The results showed that the overall antibody response was lower in asymptomatic infections than in symptomatic infections throughout the disease course. In contrast to symptomatic patients, asymptomatic patients showed a dominant IgG-response towards the RBD protein, but not IgM and IgA. Neutralizing antibody titers had linear correlations with IgA/IgM/IgG levels against SARS-CoV-2-RBD, as well as with IgG levels against multiple SARS-CoV-2 structural proteins, especially with anti-RBD or anti-S2 IgG. In addition, the sensitivity of anti-S2-IgG is better in identifying asymptomatic infections at early time post infection compared to anti-RBD-IgG. These data suggest that asymptomatic infections elicit weaker antibody responses, and primarily induce IgG antibody responses rather than IgA or IgM antibody responses. Detection of IgG against the S2 protein could supplement nucleic acid testing to identify asymptomatic patients. This study provides an antibody detection scheme for asymptomatic infections, which may contribute to epidemic prevention and control.

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

Frontiers in Immunology ◽

10.3389/fimmu.2021.686691 ◽

2021 ◽

Vol 12 ◽

Author(s):

Francesca Falconi-Agapito ◽

Karen Kerkhof ◽

Xiomara Merino ◽

Johan Michiels ◽

Marjan Van Esbroeck ◽

...

Keyword(s):

Antibody Response ◽

Acute Phase ◽

Dengue Infection ◽

Public Health Problem ◽

Antibody Responses ◽

Major Public Health Problem ◽

Serum Samples ◽

Igg Antibody ◽

Time Points ◽

Secondary Infections

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.

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Modulation of Antibody-Mediated Immune Response by Probiotics in Chickens

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.12.12.1387-1392.2005 ◽

2005 ◽

Vol 12 (12) ◽

pp. 1387-1392 ◽

Cited By ~ 98

Author(s):

Hamid R. Haghighi ◽

Jianhua Gong ◽

Carlton L. Gyles ◽

M. Anthony Hayes ◽

Babak Sanei ◽

...

Keyword(s):

Antibody Response ◽

Serum Antibody ◽

Bifidobacterium Bifidum ◽

Immunoglobulin M ◽

Antibody Responses ◽

Gut Contents ◽

Igg Antibody ◽

Mucosal Antibody ◽

Probiotic Product ◽

Phosphate Buffered Saline

ABSTRACT Probiotic bacteria, including Lactobacillus acidophilus and Bifidobacterium bifidum, have been shown to enhance antibody responses in mammals. The objective of this study was to examine the effects of a probiotic product containing the above bacteria in addition to Streptococcus faecalis on the induction of the chicken antibody response to various antigens, both systemically and in the gut. The birds received probiotics via oral gavage and subsequently were immunized with sheep red blood cells (SRBC) and bovine serum albumin (BSA) to evaluate antibody responses in serum or with tetanus toxoid (TT) to measure the mucosal antibody response in gut contents. Control groups received phosphate-buffered saline. Overall, BSA and SRBC induced a detectable antibody response as early as week 1 postimmunization (p.i.), which lasted until week 3 p.i. Probiotic-treated birds had significantly (P ≤ 0.001) more serum antibody (predominantly immunoglobulin M [IgM]) to SRBC than the birds that were not treated with probiotics. However, treatment with probiotics did not enhance the serum IgM and IgG antibody responses to BSA. Immunization with TT resulted in the presence of specific IgA and IgG antibody responses in the gut. Again, treatment with probiotics did not change the level or duration of the antibody response in the gut. In conclusion, probiotics enhance the systemic antibody response to some antigens in chickens, but it remains to be seen whether probiotics have an effect on the generation of the mucosal antibody response.

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Immune cell profiling and antibody responses in patients with COVID-19

BMC Infectious Diseases ◽

10.1186/s12879-021-06278-2 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Mitra Rezaei ◽

Shima Mahmoudi ◽

Esmaeil Mortaz ◽

Majid Marjani

Keyword(s):

T Cells ◽

Antibody Response ◽

Nk Cells ◽

Lymphocyte Subsets ◽

Immune Cell ◽

Antibody Responses ◽

P Value ◽

Serological Response ◽

Igg Antibody ◽

Lymphocyte Ratio

Abstract Background Although there are a growing number of studies on evaluating lymphocyte subset counts as prognostic factors for COVID-19 disease severity, the lymphocyte subsets’ analyses of both IgM and IgG responders and non-responders during the periods after onset of symptoms, have not been conducted yet. So, this study aimed to evaluate immune cell profiling of COVID-19 patients with and without antibody responses. Methods In this cross-sectional study, the levels of peripheral lymphocyte subsets were measured using flow cytometry in 53 patients with positive SARS-CoV-2 RT-PCR, for whom antibody testing of COVID-19 was performed. Results The white blood cell, neutrophil, and lymphocyte counts consistently decreased in the IgM and IgG non-responder group, while the differences in the median value between the two study groups were found to be statistically significant only in terms of neutrophil counts (P = 0.024 for IgM response and p-value = 0.046 for IgG response, respectively). Moreover, the level of neutrophil-to-lymphocyte ratio was observed to be significantly lower in the IgM or IgG non-responder group compared to the IgM or IgG responder group (3.6 ± 3.1 vs. 6.3 ± 4.2; p-value = 0.021). The patients with IgM antibody response had a significantly lower CD20+ lymphocytes (11% versus 15% in the groups without IgM antibody response, p-value = 0.031), The percentages of NK cells and CD4+ T cells significantly increased in the patients with IgG antibody response compared to those without IgG antibody response (13% versus 10%, p-value = 0.028, and 41.5% versus 34%; p-value = 0.03, respectively). Moreover, the patients who produced IgM or IgG antibody had significantly higher percentages of total T lymphocytes (64% versus 54%; p-value = 0.017), CD4+ T cells (41% versus 34%; p-value = 0.038), and NK cells (13% versus 9%, p-value = 0.023) compared to the group with no serological response. No significant difference was observed in the percentage of other lymphocyte subsets, including CD8+ T cells, Treg cells, and CD19+ B cells. Conclusion Our results suggest that the total T cells, CD4+ T cells, and NK cells percentages are linked to serological response. Moreover, our findings suggested that neutrophil absolute counts and neutrophil-to-lymphocyte ratio may be valuable predictors of IgM or IgG antibody response.

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Pre-vaccination and early B cell signatures predict antibody response to SARS-CoV-2 mRNA vaccine

10.1101/2021.07.06.21259528 ◽

2021 ◽

Author(s):

Lela Kardava ◽

Nicholas Rachmaninoff ◽

William Lau ◽

Clarisa Buckner ◽

Krittin Trihemasava ◽

...

Keyword(s):

Antibody Response ◽

B Cell ◽

Response Variability ◽

Antibody Responses ◽

Igg Antibody ◽

Memory B Cell ◽

Post Vaccination ◽

Highly Effective ◽

Antibody Levels ◽

Early Indicators

SARS-CoV-2 mRNA vaccines are highly effective, although weak antibody responses are seen in some individuals with correlates of immunity that remain poorly understood. Here we longitudinally dissected antibody, plasmablast, and memory B cell (MBC) responses to the two-dose Moderna mRNA vaccine in SARS-CoV-2-uninfected adults. Robust, coordinated IgA and IgG antibody responses were preceded by bursts of spike-specific plasmablasts after both doses, but earlier and more intensely after dose two. Distinct antigen-specific MBC populations also emerged post-vaccination with varying kinetics. We identified antigen non-specific pre-vaccination MBC and post-vaccination plasmablasts after dose one and their spike-specific counterparts early after dose two that correlated with subsequent antibody levels. These baseline and response signatures can thus provide early indicators of serological efficacy and explain response variability in the population.

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