Antibody Response Profiles Research Articles

Assessing mucosal antibody responses to SARS-CoV-2 in humans and mice.

Abstract COVID-19 is a respiratory disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We previously developed an enzyme-linked immunosorbent assay (ELISA) protocol to profile antibody responses to the SARS-CoV-2 Spike protein and its receptor-binding domain (RBD) in the saliva of patients with COVID-19. Anti-SARS-CoV-2 antibody responses were readily detected in saliva, peaking at 16–30 days post-symptom onset. While anti-SARS-CoV-2 IgM/IgA were found to decay, IgG responses were more long-lived, persisting up to 105 days. Now we wish to know (1) if anti-SARS-CoV-2 antibodies are generated locally in the oral cavity, (2) the relative kinetics of IgA versus IgG appearance in the oral cavity, and (3) whether salivary antibodies have the capacity to neutralize SARS-CoV-2. To answer these, I have adapted our ELISA to detect secretory component-associated SARS-CoV-2-specific antibodies. I found that 33.3% and 26.9% of COVID-19 patients were positive for secretory component-associated antibodies to Spike and RBD, respectively. Secretory component-associated antibodies correlated with antigen-specific IgA levels, particularly for the Spike antigen. Moreover, using saliva from contact-traced subjects, I found that anti-Spike/RBD IgM/IgA are detected in the saliva 7 days post-exposure, prior to IgG. Lastly, I detected Spike-specific antibody-secreting cells in lymphoid tissues draining the upper respiratory tract upon intranasal infection of K18-hACE2 mice with a non-lethal dose of SARS-CoV-2. In summary, I have provided evidence in humans and mice that a local antibody response that quickly class switches to IgA occurs in the oral cavity and draining lymph nodes upon infection with SARS-CoV-2.

Assessing Prevalence and Transmission Rates of Malaria through Simultaneous Profiling of Antibody Responses against Plasmodium and Anopheles Antigens.

Reliably assessing exposure to mosquitoes carrying malaria parasites continues to be a challenge due to the lack of reliable, highly sensitive diagnostics with high-throughput potential. Here, we describe an approach that meets these requirements by simultaneously measuring immune responses to both disease vector and pathogen, using an electro-chemiluminescence-based multiplex assay platform. While using the same logistical steps as a classic ELISA, this platform allows for the multiplexing of up to ten antigens in a single well. This simple, reproducible, quantitative readout reports the magnitude, incidence, and prevalence of malaria infections in residents of malaria-endemic areas. By reporting exposure to both insect vectors and pathogen, the approach also provides insights into the efficacy of drugs and/or other countermeasures deployed against insect vectors aimed at reducing or eliminating arthropod-borne diseases. The high throughput of the assay enables the quick and efficient screening of sera from individuals for exposure to Plasmodium even if they are taking drug prophylaxis. We applied this assay to samples collected from controlled malaria infection studies, as well as those collected in field studies in malaria-endemic regions in Uganda and Kenya. The assay was sensitive to vector exposure, malaria infection, and endemicity, demonstrating its potential for use in malaria serosurveillance.

Longitudinal profile of antibody response to SARS-CoV-2 in patients with COVID-19 in a setting from Sub-Saharan Africa: A prospective longitudinal study.

BackgroundSerological testing for SARS-CoV-2 plays an important role for epidemiological studies, in aiding the diagnosis of COVID-19, and assess vaccine responses. Little is known on dynamics of SARS-CoV-2 serology in African settings. Here, we aimed to characterize the longitudinal antibody response profile to SARS-CoV-2 in Ethiopia.MethodsIn this prospective study, a total of 102 PCR-confirmed COVID-19 patients were enrolled. We obtained 802 plasma samples collected serially. SARS-CoV-2 antibodies were determined using four lateral flow immune-assays (LFIAs), and an electrochemiluminescent immunoassay. We determined longitudinal antibody response to SARS-CoV-2 as well as seroconversion dynamics.ResultsSerological positivity rate ranged between 12%-91%, depending on timing after symptom onset. There was no difference in positivity rate between severe and non-severe COVID-19 cases. The specificity ranged between 90%-97%. Agreement between different assays ranged between 84%-92%. The estimated positive predictive value (PPV) for IgM or IgG in a scenario with seroprevalence at 5% varies from 33% to 58%. Nonetheless, when the population seroprevalence increases to 25% and 50%, there is a corresponding increases in the estimated PPVs. The estimated negative-predictive value (NPV) in a low seroprevalence scenario (5%) is high (>99%). However, the estimated NPV in a high seroprevalence scenario (50%) for IgM or IgG is reduced significantly to 80% to 85%. Overall, 28/102 (27.5%) seroconverted by one or more assays tested, within a median time of 11 (IQR: 9–15) days post symptom onset. The median seroconversion time among symptomatic cases tended to be shorter when compared to asymptomatic patients [9 (IQR: 6–11) vs. 15 (IQR: 13–21) days; p = 0.002]. Overall, seroconversion reached 100% 5.5 weeks after the onset of symptoms. Notably, of the remaining 74 COVID-19 patients included in the cohort, 64 (62.8%) were positive for antibody at the time of enrollment, and 10 (9.8%) patients failed to mount a detectable antibody response by any of the assays tested during follow-up.ConclusionsLongitudinal assessment of antibody response in African COVID-19 patients revealed heterogeneous responses. This underscores the need for a comprehensive evaluation of seroassays before implementation. Factors associated with failure to seroconvert needs further research.

Antibody attributes that predict the neutralization and effector function of polyclonal responses to SARS-CoV-2

BackgroundWhile antibodies can provide significant protection from SARS-CoV-2 infection and disease sequelae, the specific attributes of the humoral response that contribute to immunity are incompletely defined.MethodsWe employ machine learning to relate characteristics of the polyclonal antibody response raised by natural infection to diverse antibody effector functions and neutralization potency with the goal of generating both accurate predictions of each activity based on antibody response profiles as well as insights into antibody mechanisms of action.ResultsTo this end, antibody-mediated phagocytosis, cytotoxicity, complement deposition, and neutralization were accurately predicted from biophysical antibody profiles in both discovery and validation cohorts. These models identified SARS-CoV-2-specific IgM as a key predictor of neutralization activity whose mechanistic relevance was supported experimentally by depletion.ConclusionsValidated models of how different aspects of the humoral response relate to antiviral antibody activities suggest desirable attributes to recapitulate by vaccination or other antibody-based interventions.

Naturally acquired antibody response to a Plasmodium falciparum chimeric vaccine candidate GMZ2.6c and its components (MSP-3, GLURP, and Pfs48/45) in individuals living in Brazilian malaria-endemic areas

BackgroundThe GMZ2.6c malaria vaccine candidate is a multi-stage Plasmodium falciparum chimeric protein which contains a fragment of the sexual-stage Pfs48/45-6C protein genetically fused to GMZ2, a fusion protein of GLURP and MSP-3, that has been shown to be well tolerated, safe and immunogenic in clinical trials performed in a malaria-endemic area of Africa. However, there is no data available on the antigenicity or immunogenicity of GMZ2.6c in humans. Considering that circulating parasites can be genetically distinct in different malaria-endemic areas and that host genetic factors can influence the immune response to vaccine antigens, it is important to verify the antigenicity, immunogenicity and the possibility of associated protection in individuals living in malaria-endemic areas with different epidemiological scenarios. Herein, the profile of antibody response against GMZ2.6c and its components (MSP-3, GLURP and Pfs48/45) in residents of the Brazilian Amazon naturally exposed to malaria, in areas with different levels of transmission, was evaluated.MethodsThis study was performed using serum samples from 352 individuals from Cruzeiro do Sul and Mâncio Lima, in the state of Acre, and Guajará, in the state of Amazonas. Specific IgG, IgM, IgA and IgE antibodies and IgG subclasses were detected by Enzyme-Linked Immunosorbent Assay.ResultsThe results showed that GMZ2.6c protein was widely recognized by naturally acquired antibodies from individuals of the Brazilian endemic areas with different levels of transmission. The higher prevalence of individuals with antibodies against GMZ2.6c when compared to its individual components may suggest an additive effect of GLURP, MSP-3, and Pfs48/45 when inserted in a same construct. Furthermore, naturally malaria-exposed individuals predominantly had IgG1 and IgG3 cytophilic anti-GMZ2.6c antibodies, an important fact considering that the acquisition of anti-malaria protective immunity results from a delicate balance between cytophilic/non-cytophilic antibodies. Interestingly, anti-GMZ2.6c antibodies seem to increase with exposure to malaria infection and may contribute to parasite immunity.ConclusionsThe data showed that GMZ2.6c protein is widely recognized by naturally acquired antibodies from individuals living in malaria-endemic areas in Brazil and that these may contribute to parasite immunity. These data highlight the importance of GMZ2.6c as a candidate for an anti-malarial vaccine.

Disease characteristics and serological responses in patients with differing severity of COVID-19 infection: A longitudinal cohort study in Dhaka, Bangladesh.

BackgroundCOVID-19 caused by SARS-CoV-2 ranges from asymptomatic to severe disease and can cause fatal and devastating outcome in many cases. In this study, we have compared the clinical, biochemical and immunological parameters across the different disease spectrum of COVID-19 in Bangladeshi patients.Methodology/Principal findingsThis longitudinal study was conducted in two COVID-19 hospitals and also around the community in Dhaka city in Bangladesh between November 2020 to March 2021. A total of 100 patients with COVID-19 infection were enrolled and classified into asymptomatic, mild, moderate and severe cases (n = 25/group). In addition, thirty age and sex matched healthy participants were enrolled and 21 were analyzed as controls based on exclusion criteria. After enrollment (study day1), follow-up visits were conducted on day 7, 14 and 28 for the cases.Older age, male gender and co-morbid conditions were the risk factors for severe COVID-19 disease. Those with moderate and severe cases of infection had low lymphocyte counts, high neutrophil counts along with a higher neutrophil-lymphocyte ratio (NLR) at enrollment; this decreased to normal range within 42 days after the onset of symptom. At enrollment, D-dimer, CRP and ferritin levels were elevated among moderate and severe cases. The mild, moderate, and severe cases were seropositive for IgG antibody by day 14 after enrollment. Moderate and severe cases showed significantly higher IgM and IgG levels of antibodies to SARS-CoV-2 compared to mild and asymptomatic cases.Conclusion/SignificanceWe report on the clinical, biochemical, and hematological parameters associated with the different severity of COVID-19 infection. We also show different profile of antibody response against SARS-CoV-2 in relation to disease severity, especially in those with moderate and severe disease manifestations compared to the mild and asymptomatic infection.

Antibody Response Profile in COVID-19 Infection in Healthcare Workers: Insights from a Study at a Reference Laboratory

Introduction: The Coronavirus Disease 2019 (COVID-19) pandemic has imposed an unprecedented burden on our healthcare system. Serological testing for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) antibodies serves as an useful marker for determining an infection by the virus in the recent past and the immune response. The immune response, including the humoral response to the infection is one of them and the knowledge in this area is still evolving. Virus specific antibodies are expected to help in eliminating the virus and to provide protective immunity against reinfection. Aim: To serially monitor the total antibody response to SARSCoV-2 in order to gain better insight into the duration of antibody persistence. Materials and Methods: This prospective observational study was conducted in 66 Healthcare Workers (HCW) with a history of Reverse Transcription- Polymerase Chain Reaction (RTPCR) proven COVID-19 infection. The study was conducted between May 2020 to April 2021 at the Suburban diagnostics Central Processing Laboratory, Mumbai, Maharashtra, India. Serum samples were serially examined for the presence of total antibodies against the Nucleocapsid (N) protein of SARS-CoV-2 upto 180 days postinfection. A further follow-up examination was done at 360 days. A qualitative Electrochemiluminescence Immunoassay (ECLIA) assay was used for assessment of the antibody response. The chi-square or Fisher-exact test was used to compare categorical variables and the Mann-Whitney U test, Kruskal Wallis test and student t-test were used to compare continuous variables across groups. For assessing relationship between variables, the Pearson test or linear regression were used as appropriate. Results: Out of 66 healthcare workers, 32 were male (48.5%) and 34 were females (51.5%) with the median age of 29.5 years. Out of 66 cases, 62 (94%) cases developed antibodies against SARS-CoV-2 at different time intervals, 48 cases during the 14- 30 day interval, 10 cases during the 31-60 day interval, three cases during the 61-90 day interval and one case during the 90-120 days interval. Thirty one out of 35 (88%) cases that could be followed-up at 360 days showed persistence of antibodies. No patient reported symptoms which would warrant a repeat RT-PCR test. Conclusion: This study showed that the antibody response to SARS-CoV-2 virus was sustained for 12 months postinfection in most cases. The absence of fresh infection in these cases during the study period suggests that the antibodies might protect against reinfection with the virus. So, it may be safe to defer vaccination in postinfection cases by 6-9 months thereby saving precious resources.

Systematic profiling of SARS-CoV-2-specific IgG responses elicited by an inactivated virus vaccine identifies peptides and proteins for predicting vaccination efficacy

One of the best ways to control COVID-19 is vaccination. Among the various SARS-CoV-2 vaccines, inactivated virus vaccines have been widely applied in China and many other countries. To understand the underlying protective mechanism of these vaccines, it is necessary to systematically analyze the humoral responses that are triggered. By utilizing a SARS-CoV-2 microarray with 21 proteins and 197 peptides that fully cover the spike protein, antibody response profiles of 59 serum samples collected from 32 volunteers immunized with the inactivated virus vaccine BBIBP-CorV were generated. For this set of samples, the microarray results correlated with the neutralization titers of the authentic virus, and two peptides (S1-5 and S2-22) were identified as potential biomarkers for assessing the effectiveness of vaccination. Moreover, by comparing immunized volunteers to convalescent and hospitalized COVID-19 patients, the N protein, NSP7, and S2-78 were identified as potential biomarkers for differentiating COVID-19 patients from individuals vaccinated with the inactivated SARS-CoV-2 vaccine. The comprehensive profile of humoral responses against the inactivated SARS-CoV-2 vaccine will facilitate a deeper understanding of the vaccine and provide potential biomarkers for inactivated virus vaccine-related applications.

Longitudinal Profile of Antibody Response to SARS-CoV-2 in Patients with COVID-19 in a Setting from Sub–Saharan Africa: A Prospective Longitudinal Study

Background: Serological testing for SARS-CoV-2 plays an important role for epidemiological studies, in aiding the diagnosis of COVID-19, and assess vaccine responses. Little is known on dynamics of SARS-CoV-2 serology in African settings. Here, we aimed to characterize the longitudinal antibody response profile to SARS-CoV-2 in Ethiopia.Methods: In this prospective study, a total of 102 PCR-confirmed COVID-19 patients were enrolled. We obtained 802 plasma samples collected serially. SARS-CoV-2 antibodies were determined using four lateral flow immune-assays (LFIAs), and an electrochemiluminescent immunoassay. We determined the sensitivity, specificity, as well as seroconversion dynamics.Findings: Serological positivity rate ranged between 12%-91%, depending on timing after symptom onset. There was no difference in positivity rate between severe and non-severe COVID-19 cases. The specificity ranged between 90%-99%. Agreement between different assays ranged between 84%-92%. Overall, 28/102 (27.5%) seroconverted by one or more assays tested, within a median time of 11 (IQR: 9–15) days post symptom onset. The median seroconversion time among symptomatic cases tended to be shorter when compared to asymptomatic patients [9 (IQR: 6–11) vs. 15 (IQR: 13–21) days; p=0.002]. Overall, seroconversion reached 100% 5.5 weeks after the onset of symptoms. Notably, 10 (9.8%) patients failed to mount a detectable antibody response by any of the assays tested during of follow-up.Interpretation: Longitudinal assessment of antibody response in African COVID-19 patients revealed heterogeneous responses. This underscores the need for a comprehensive evaluation of seroassays before implementation. Factors associated with failure to seroconvert needs further research.Funding: The European and Developing Countries Clinical Trial Partnership (EDCTP) – European Union.Declaration of Interest: DW is European and Developing Countries Clinical Trials Partnership (EDCTP) Senior Research Fellow, and received funding for EvaLAMP project on Leishmaniasis Diagnostics; he serves as Strategic and Scientific Advisory Board of the Research Networks for Health Innovations in Sub-Saharan Africa (German Federal Ministry of Education and Research), and has received an honorarium for lectures and presentations from the Ethiopian Ministry of Science and Higher Education. TRW is employee of PharmAccess Foundation, is Board Member of Mondial Diagnostics, and Advisory Board member of Healthinc, The Netherlands. All other authors have no declarations to disclose.Ethical Approval: The study protocol was reviewed and approved by the Health Research Ethics Review Committee of Mekelle University College of Health Sciences (#ERC 1769/2020).

Stepwise Conformational Stabilization of a HIV-1 Clade C Consensus Envelope Trimer Immunogen Impacts the Profile of Vaccine-Induced Antibody Responses.

Stabilization of the HIV-1 Envelope glycoprotein trimer (Env) in its native pre-fusion closed conformation is regarded as one of several requirements for the induction of neutralizing antibody (nAb) responses, which, in turn, will most likely be a prerequisite for the development of an efficacious preventive vaccine. Here, we systematically analyzed how the stepwise stabilization of a clade C consensus (ConC) Env immunogen impacts biochemical and biophysical protein traits such as antigenicity, thermal stability, structural integrity, and particle size distribution. The increasing degree of conformational rigidification positively correlates with favorable protein characteristics, leading to optimized homogeneity of the protein preparations, increased thermal stability, and an overall favorable binding profile of structure-dependent broadly neutralizing antibodies (bnAbs) and non-neutralizing antibodies (non-nAbs). We confirmed that increasing the structural integrity and stability of the Env trimers positively correlates with the quality of induced antibody responses by the immunogens. These and other data contribute to the selection of ConCv5 KIKO as novel Env immunogens for use within the European Union’s H2020 Research Consortium EHVA (European HIV Alliance) for further preclinical analysis and phase 1 clinical development.

Prevalence of SARS-CoV-2 infection and dynamics of antibodies response among previously undiagnosed healthcare workers in a university hospital: A prospective cohort study

BackgroundHealthcare workers (HCWs) are a presumed high-risk population for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Identifying factors associated with seroprevalence can help establish better practices in healthcare settings. In this study, we evaluate prevalence of SARS-CoV-2 infection among previously undiagnosed HCWs and describe profiling of antibody responses against SARS-CoV-2, including neutralizing antibodies (NAbs). MethodsWe analyzed a cohort of 386 HCWs in a university hospital in Egypt and 725 volunteers not affiliated to any healthcare facility (non-healthcare workers - NHCWs). Participants provided a nasopharyngeal swab and serum samples for SARS-CoV-2 nucleic acid and SARS-CoV-2-specific antibodies, respectively. HCWs who tested positive by either test were sequentially monitored. ResultsAt baseline, point prevalence of viral carriage was 11.4% in HCWs (n = 44/386) and 11.9% in NHCWs (86/725). The cumulative prevalence of SARS-CoV-2 infection among HCWs considering all studies was 25.6%, which was statistically lower than in NHCWs (41.0%). Prevalence was greatest among janitorial staff (45.9%) and the most affected departments were gastroenterology (31.1%), and emergency medicine (30.0%). Prior anosmia, fever or headache were associated with higher odds of positivity for SARS-CoV-2 infection. Regarding serial antibody measurements, RT-PCR-positive HCWs displayed IgG detection rates of 29.5%, 70% and 60% at visit 1, visit 2 and visit 3, respectively with slow decline of median IgG antibody titers, whereas, corresponding detection rates for total Ig antibodies were 50%, 90.3%, and 88.9%, respectively with increasing median titers. NAbs measured at each time point were positively correlated with total Ig levels, whereas IgG levels were positively correlated with NAbs at visit 1 and visit 3. ConclusionOur results demonstrate lower cumulative prevalence of SARS-CoV-2 infection in HCWs than general population and suggest that asymptomatic HCWs exhibit considerable IgG and total Ig antibodies response as well as NAbs for up to 120 days, with positive correlation in between.

Temporal Profiles of Antibody Responses, Cytokines, and Survival of COVID-19 Patients: A Retrospective Cohort.

The longitudinal immunologic status of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients and its association with the clinical outcome are barely known. Thus, we sought to analyze the temporal profiles of specific antibodies, as well as the associations between the antibodies, proinflammatory cytokines, and survival of patients with coronavirus disease 2019 (COVID-19). A total of 1830 laboratory-confirmed COVID-19 cases were recruited. The temporal profiles of the virus, antibodies, and cytokines of the patients until 12 weeks since illness onset were fitted by the locally weighted scatter plot smoothing method. The mediation effect of cytokines on the associations between antibody responses and survival were explored by mediation analysis. Of the 1830 patients, 1435 were detectable for SARS-CoV-2, while 395 were positive in specific antibodies only. Of the 1435 patients, 2.4% presented seroconversion for neither immunoglobulin G (IgG) nor immunoglobulin M (IgM) during hospitalization. The seropositive rates of IgG and IgM were 29.6% and 48.1%, respectively, in the first week, and plateaued within five weeks. For the patients discharged from the hospital, the IgM decreased slowly, while high levels of IgG were maintained at around 188 AU·mL−1 for the 12 weeks since illness onset. In contrast, in the patients who subsequently died, IgM declined rapidly and IgG dropped to 87 AU·mL−1 at the twelfth week. Elevated interleukin-6, interleukin-8, interleukin-10, interleukin-1β, interleukin-2R, and tumor necrosis factor-α levels were observed in the deceased patients in comparison with the discharged patients, and 12.5% of the association between IgG level and mortality risk was mediated by these cytokines. Our study deciphers the temporal profiles of SARS-CoV-2-specific antibodies within the 12 weeks since illness onset and indicates the protective effect of antibody response on survival, which may help to guide prognosis estimation.

High variation in immune responses and parasite phenotypes in naturally acquired Trypanosoma cruzi infection in a captive non-human primate breeding colony in Texas, USA.

Trypanosoma cruzi, the causative agent of human Chagas disease, is endemic to the southern region of the United States where it routinely infects many host species. The indoor/outdoor housing configuration used in many non-human primate research and breeding facilities in the southern of the USA provides the opportunity for infection by T. cruzi and thus provides source material for in-depth investigation of host and parasite dynamics in a natural host species under highly controlled and restricted conditions. For cynomolgus macaques housed at such a facility, we used a combination of serial blood quantitative PCR (qPCR) and hemoculture to confirm infection in >92% of seropositive animals, although each method alone failed to detect infection in >20% of cases. Parasite isolates obtained from 43 of the 64 seropositive macaques were of 2 broad genetic types (discrete typing units, (DTU's) I and IV); both within and between these DTU groupings, isolates displayed a wide variation in growth characteristics and virulence, elicited host immune responses, and susceptibility to drug treatment in a mouse model. Likewise, the macaques displayed a diversity in T cell and antibody response profiles that rarely correlated with parasite DTU type, minimum length of infection, or age of the primate. This study reveals the complexity of infection dynamics, parasite phenotypes, and immune response patterns that can occur in a primate group, despite being housed in a uniform environment at a single location, and the limited time period over which the T. cruzi infections were established.

Association of Age With SARS-CoV-2 Antibody Response

Accumulating evidence suggests that children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are more likely to manifest mild symptoms and are at a lower risk of developing severe respiratory disease compared with adults. It remains unknown how the immune response in children differs from that of adolescents and adults. To investigate the association of age with the quantity and quality of SARS-CoV-2 antibody responses. This cross-sectional study used 31 426 SARS-CoV-2 antibody test results from pediatric and adult patients. Data were collected from a New York City hospital from April 9 to August 31, 2020. The semiquantitative immunoglobin (Ig) G levels were compared between 85 pediatric and 3648 adult patients. Further analysis of SARS-CoV-2 antibody profiles was performed on sera from 126 patients aged 1 to 24 years. SARS-CoV-2 antibody positivity rates and IgG levels were evaluated in patients from a wide range of age groups (1-102 years). SARS-CoV-2 IgG level, total antibody (TAb) level, surrogate neutralizing antibody (SNAb) activity, and antibody binding avidity were compared between children (aged 1-10 years), adolescents (aged 11-18 years), and young adults (aged 19-24 years). Among 31 426 antibody test results (19 797 [63.0%] female patients), with 1194 pediatric patients (mean [SD] age, 11.0 [5.3] years) and 30 232 adult patients (mean [SD] age, 49.2 [17.1] years), the seroprevalence in the pediatric (197 [16.5%; 95% CI, 14.4%-18.7%]) and adult (5630 [18.6%; 95% CI, 18.2%-19.1%]) patient populations was similar. The SARS-CoV-2 IgG level showed a negative correlation with age in the pediatric population (r = -0.45, P < .001) and a moderate but positive correlation with age in adults (r = 0.24, P < .001). Patients aged 19 to 30 years exhibited the lowest IgG levels (eg, aged 25-30 years vs 1-10 years: 99 [44-180] relative fluorescence units [RFU] vs 443 [188-851] RFU). In the subset cohort aged 1 to 24 years, IgG, TAb, SNAb and avidity were negatively correlated with age (eg, IgG: r = -0.51; P < .001). Children exhibited higher median (IQR) IgG levels, TAb levels, and SNAb activity compared with adolescents (eg, IgG levels: 473 [233-656] RFU vs 191 [82-349] RFU; P < .001) and young adults (eg, IgG levels: 473 [233-656] RFU vs 85 [38-150] RFU; P < .001). Adolescents also exhibited higher median (IQR) TAb levels, IgG levels, and SNAb activity than young adults (eg, TAb levels: 961 [290-2074] RFU vs 370 [125-697]; P = .006). In addition, children had higher antibody binding avidity compared with young adults, but the difference was not significant. The results of this study suggest that SARS-CoV-2 viral specific antibody response profiles are distinct in different age groups. Age-targeted strategies for disease screening and management as well as vaccine development may be warranted.

Profile of specific antibodies to the SARS-CoV-2.

In this work, we studied the profile of IgM and IgG antibody responses to SARS-CoV-2 in 32 patients with COVID-19 from day 1 to day 24. IgM remained measurable for a much shorter period than IgG, suggesting that IgG antibody may represent the primary immune response.

What are protective antibody responses to pandemic SARS-CoV-2?

Human antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hold intense interest, with research efforts directed at optimizing antibody-based interventions and monitoring immune status. By relating individual variations in antibody response to coronavirus disease 2019 (COVID-19) severity, beneficial antiviral immune responses may be identified in detail. In this issue of the JCI, Secchi and collaborators describe antibody response profiles in 509 patients with COVID-19 from Italy during the 2020 pandemic. The research team found that multiple antibody types to multiple SARS-CoV-2 antigens developed over four weeks. Notably, IgG against the spike receptor binding domain (RBD) was predictive of survival and IgA against the viral spike protein (S protein) associated with rapid virologic clearance. These results may help guide selection of convalescent plasma, hyperimmune products, monoclonal antibodies, and vaccine strategies for COVID-19.

Strongyloides-specific IgA, IgG and IgG immune complex profile in patients with pulmonary tuberculosis.

To describe an anti-Strongyloides IgA, IgG and IgG immune complex antibody response profile in patients with pulmonary tuberculosis. Saliva and serum samples were collected from 100 individuals: group I, 50 apparently healthy individuals; and group II, 50 pulmonary tuberculosis patients. The IgA, IgG and IgG immune complex detection were carried out via an ELISA immunoenzymatic test. Optical density medians in saliva samples of IgA antibody (median of 7.21) and IgG-IC (median of 4.95) were significantly higher in tuberculosis group compared to control individuals (median IgA of 3.93 and IgG-IC of 2.38). This study presents antibody data to the field of pulmonary tuberculosis and strongyloidiasis coinfection, including saliva samples, and especially IgG immune complex detection.

M-protein based vaccine induces immunogenicity and protection from Streptococcus pyogenes when delivered on a high-density microarray patch (HD-MAP)

We evaluated vaccination against Streptococcus pyogenes with the candidate vaccine, J8-DT, delivered by a high-density microarray patch (HD-MAP). We showed that vaccination with J8-DT eluted from a coated HD-MAP (J8-DT/HD-MAP), induced similar total IgG responses to that generated by vaccination with J8-DT adjuvanted with Alum (J8-DT/Alum). We evaluated the effect of dose reduction and the number of vaccinations on the antibody response profile of vaccinated mice. A reduction in the number of vaccinations (from three to two) with J8-DT/HD-MAP induced comparable antibody responses to three vaccinations with intramuscular J8-DT/Alum. Vaccine-induced protection against an S. pyogenes skin challenge was assessed. J8-DT/HD-MAP vaccination led to a significant reduction in the number of S. pyogenes colony forming units in skin (92.9%) and blood (100%) compared to intramuscular vaccination with unadjuvanted J8-DT. The protection profile was comparable to that of intramuscular J8-DT/Alum. J8-DT/HD-MAP induced a shift in the antibody isotype profile, with a bias towards Th1-related isotypes, compared to J8-DT/Alum (Th2 bias). Based on the results of this study, the use of J8-DT/HD-MAP should be considered in future clinical development and control programs against S. pyogenes. Furthermore, the innate characteristics of the technology, such as vaccine stability and increased coverage, ease of use, reduction of sharp waste and the potential reduction of dose may be advantageous compared to current vaccination methods.

Serologic Response to SARS-CoV-2 in COVID-19 Patients with Different Severity.

The immense patient number caused by coronavirus disease 2019 (COVID-19) global pandemic brings the urge for more knowledge about its immunological features, including the profile of basic immune parameters. In this study, eighty-eight reported COVID-19 patients in Wuhan were recruited from January to February, 2020, including 32 severe/critical cases and 56 mild/moderate cases. Their mean age was 56.43 years (range 17–83) and gender ratio (male/female) was 43:45. We tested SARS-CoV-2 RNA with commercial kits, investigated the level of serologic IgM and IgG antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using magnetic particle chemiluminescence immunoassays, and compared the results of serologic tests and nucleic acid test (NAT). Among 88 patients, 95.45% were confirmed as positive by the combination of NAT and antibody test, which was significantly higher (P < 0.001) than by single nucleic acid test (73.86%) or serologic test (65.91%). Then the correlation between temporal profile and the level of antibody response was analyzed. It showed that seroconversion started on day 5 after disease onset and IgG level was rose earlier than IgM. Comparison between patients with different disease severity suggested early seroconversion and high antibody titer were linked with less severe clinical symptoms. These results supported the combination of serologic testing and NAT in routine COVID-19 diagnosis and provided evidence on the temporal profile of antibody response in patients with different disease severity.

Subclass Profile of IgG Antibody Response to Gluten Differentiates Nonceliac Gluten Sensitivity From Celiac Disease

Subclass Profile of IgG Antibody Response to Gluten Differentiates Nonceliac Gluten Sensitivity From Celiac Disease