Immune response toTrichinellaepitopes: the antiphosphorylcholine plaque-forming cell response during the biological cycle

Parasitology ◽  
1987 ◽  
Vol 94 (3) ◽  
pp. 543-553 ◽  
Author(s):  
F. M. Ubeira ◽  
J. Leiro ◽  
M. T. Santamarina ◽  
T. G. Villa ◽  
M. L. Sanmartín-Durán

Phosphorylcholine (PC), an immunodominant component of the cell wall of certain bacteria, fungi and nematodes, is known to induce low anti-PC antibody levels during natural infection byTrichinella spiralis. This article reports a study in which spleen cells from BCF1 mice infected withTrichinellasp. larvae were found to produce large numbers of direct haemolytic plaques in response to PC conjugated to sheep red blood cells (SRBC) after muscle-encysted larvae had been killed by treatment with mebendazole. Inhibition of the response by PC-chloride, immunodiffusion and immunoelectrophoretic studies with the anti-PC IgA (TEPC-15) and anti-idiotype T15 serum assays showed the plaque-forming cell (PFC) response to be specific for PC. The absence of haemolytic plaques when unconjugated SRBC or TNP-SRBC were used as indicator cells ruled out involvement of a polyclonal response. Greatest anti-PC PFC response was found to be associated with a microsomal fraction designated FCpl, a particulate fraction behaving as a thymus-dependent antigen. The FCpl fractions from all four strains ofTrichinellaemployed induced anti-PC PFC responses when injected into mice. These results suggest that FCpl is a suitable antigen for use in detailed studies of immune responses toTrichinellaand related parasites.

2021 ◽  
Vol 9 (1) ◽  
pp. 11-16
Author(s):  
AR Awan ◽  
OL Tulp ◽  
HJ Field

Equine herpes virus (EHV-1) causes respiratory infections in equine, and results in abortion, paresis, neonatal death, and retinopathy and the virus may become latent following initial infection. Virus entry is via the respiratory route, and the virus replicates in the host in ciliated and non-ciliated epithelial cells of the respiratory tract and in Type 1 and Type 2 pneumocytes in the lung parenchyma. After viral replication in the respiratory system, the virus can become disseminated to other parts of body via viraemic cells. The virus also can cross the placenta which leads to abortion of live or dead fetuses without premonitory signs. Infected horses show transient immunity after natural or experimental infection and immune responses to EHV-1, but the immunoprotective status begins to decline after a few months of active infection. Due to the transient immune response, recovered horses are not immunoprotected and thus are prone to subsequent re-infection. Immunity is not long lived after experimental or natural infection, and as a result the development of an effective vaccine has remained a challenge. In this study viraemic cells were studied in a murine EHV-1 infection model. Mice were infected intranasally and viraemic cells were studied on days three and five which occurs during the peak of the infection. The results of this study may help to identify the nature of viraemic cells and their role in the transient immune response to infection. Buffy coat cells and lungs were removed and stained with a fluorescent antibody test for EHV-1 antigen, and lung specimens were subjected to transmission electron microscopy. Both techniques confirmed the presence of viraemic cells in lung tissues. These viraemic cells were further stained for EHV-1 antigen, and for CD4 or CD8 biomarkers and results are discussed re: pathogenesis of EHV-1 infection, identification of viraemic cells in a murine model and possible link of viraemia to transient immune responses in EHV-1 infection, which demonstrate the validity of this murine model for the investigation of the cytopathologic mechanism and sequelae of EHV manifestation in this model.


2020 ◽  
Author(s):  
Jianmin Zuo ◽  
Alex Dowell ◽  
Hayden Pearce ◽  
Kriti Verma ◽  
Heather Long ◽  
...  

Abstract The immune response to SARS-CoV-2 is critical in both controlling primary infection and preventing re-infection. However, there is concern that immune responses following natural infection may not be sustained and that this may predispose to recurrent infection. We analysed the magnitude and phenotype of the SARS-CoV-2 cellular immune response in 100 donors at six months following primary infection and related this to the profile of antibody level against spike, nucleoprotein and RBD over the previous six months. T-cell immune responses to SARS-CoV-2 were present by ELISPOT or ICS analysis in all donors and are characterised by predominant CD4+ T cell responses with strong IL-2 cytokine expression. Median T-cell responses were 50% higher in donors who had experienced an initial symptomatic infection indicating that the severity of primary infection establishes a ‘setpoint’ for cellular immunity that lasts for at least 6 months. The T-cell responses to both spike and nucleoprotein/membrane proteins were strongly correlated with the peak antibody level against each protein. The rate of decline in antibody level varied between individuals and higher levels of nucleoprotein-specific T cells were associated with preservation of NP-specific antibody level although no such correlation was observed in relation to spike-specific responses. In conclusion, our data are reassuring that functional SARS-CoV-2-specific T-cell responses are retained at six months following infection although the magnitude of this response is related to the clinical features of primary infection.


2021 ◽  
Author(s):  
Raymond T. Suhandynata ◽  
Nicholas J. Bevins ◽  
Jenny T. Tran ◽  
Deli Huang ◽  
Melissa A. Hoffman ◽  
...  

AbstractBackgroundThe severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected over 110 million individuals and led to 2.5 million deaths worldwide. As more individuals are vaccinated, the clinical performance and utility of SARS-CoV-2 serology platforms needs to be evaluated.MethodsThe ability of four commercial SARS-CoV-2 serology platforms to detect previous infection or vaccination were evaluated using a cohort of 53 SARS-CoV-2 PCR-positive patients, 89 SARS-CoV-2-vaccinated healthcare workers (Pfizer or Moderna), and 127 SARS-CoV-2 negative patients. Serology results were compared to a cell based SARS-CoV-2 pseudovirus (PSV) neutralizing antibodies assay.ResultsThe Roche S-(spike) antibody and Diazyme neutralizing antibodies (NAbs) assays detected adaptive immune response in 100.0% and 90.1% of vaccinated individuals who received two-doses of vaccine (initial and booster), respectively. The Roche N-(nucleocapsid) antibody assay and Diazyme IgG assay did not detect adaptive immune response in vaccinated individuals. The Diazyme Nabs assay correlated with the PSV SARS-CoV-2 ID50 neutralization titers (R2= 0.70), while correlation of the Roche S-antibody assay was weaker (R2= 0.39). Median PSV SARS-CoV-2 ID50 titers more than doubled in vaccinated individuals who received two-doses of the Moderna vaccine (ID50: 597) compared to individuals that received a single dose (ID50: 284).ConclusionsThe Roche S-antibody and Diazyme NAbs assays robustly detected adaptive immune responses in SARS-CoV-2 vaccinated individuals and SARS-CoV-2 infected individuals. The Diazyme NAbs assay strongly correlates with the PSV SARS-CoV-2 NAbs in vaccinated individuals. Understanding the reactivity of commercially available serology platforms is important when distinguishing vaccination response versus natural infection.SummaryThe Roche S (spike protein)-antibody and Diazyme neutralizing-antibodies (NAbs) assays were evaluated for their clinical utility in the detection of SARS-CoV-2 related adaptive immune responses by testing SARS-CoV-2 PCR-confirmed patients, SARS-CoV-2-vaccinated individuals, and SARS-CoV-2-negative individuals. Commercial serology results were compared to results generated using a cell-based SARS-CoV-2 pseudovirus (PSV) NAbs assay and previously validated SARS-CoV-2 commercial serology assays (Roche N (nucleocapsid protein) antibody and Diazyme IgG). We demonstrate that the Roche S-antibody and Diazyme NAbs assays detected adaptive immune response in SARS-CoV-2 vaccinated individuals and the presence of SARS-CoV-2 PSV NAbs. The Roche S-antibody assay had an observed positive percent agreement (PPA) of 100% for individuals who received two doses of the Pfizer or Moderna vaccine. By contrast, the Roche N assay and Diazyme IgG assay did not detect vaccine adaptive immune responses. Our findings also indicate that the Diazyme NAbs assay correlates strongly with the levels of SARS-CoV-2 ID50 neutralization titers using the PSV Nab assay in vaccinated individuals.


1974 ◽  
Vol 140 (3) ◽  
pp. 648-659 ◽  
Author(s):  
Judith A. Kapp ◽  
Carl W. Pierce ◽  
Stuart Schlossman ◽  
Baruj Benacerraf

In recent studies we have found that GAT not only fails to elicit a GAT-specific response in nonresponder mice but also specifically decreases the ability of nonresponder mice to develop a GAT-specific PFC response to a subsequent challenge with GAT bound to the immunogenic carrier, MBSA. Studies presented in this paper demonstrate that B cells from nonresponder, DBA/1 mice rendered unresponsive by GAT in vivo can respond in vitro to GAT-MBSA if exogenous, carrier-primed T cells are added to the cultures. The unresponsiveness was shown to be the result of impaired carrier-specific helper T-cell function in the spleen cells of GAT-primed mice. Spleen cells from GAT-primed mice specifically suppressed the GAT-specific PFC response of spleen cells from normal DBA/1 mice incubated with GAT-MBSA. This suppression was prevented by pretreatment of GAT-primed spleen cells with anti-θ serum plus C or X irradiation. Identification of the suppressor cells as T cells was confirmed by the demonstration that suppressor cells were confined to the fraction of the column-purified lymphocytes which contained θ-positive cells and a few non-Ig-bearing cells. The significance of these data to our understanding of Ir-gene regulation of the immune response is discussed.


Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 345
Author(s):  
Carla Morales-Ferré ◽  
Ignasi Azagra-Boronat ◽  
Malén Massot-Cladera ◽  
Àngels Franch ◽  
Margarida Castell ◽  
...  

Rotaviruses (RVs) are the leading pathogens causing severe and acute diarrhea in children and animals. It is well known that sex contributes to shaping immune responses, thus it could also influence the incidence and severity of the RV infection. The aim of this study was to analyze the influence of sexual dimorphism on RV infection and its antibody (Ab) immune response in a suckling rat model. Neonatal suckling rats were intragastrically RV-inoculated and clinical indexes derived from fecal samples, as well as immune variables were evaluated. Higher severity of diarrhea, fecal weight and viral elimination were observed in males compared to females (p < 0.05). Regarding the adaptative immunity, the RV shaped the immune response to lower IgG1 levels and an increased Th1/Th2-associated Ab response (p < 0.05). Although females had lower IgG2a levels than males (p < 0.05), the specific anti-RV antibody levels were not sex influenced. In fact, at this age the passive transfer of anti-RV antibodies through breast milk was the critical factor for clustering animals, independently of their sex. It can be concluded that male and female diarrhea severity in RV infection is slightly influenced by sexual dimorphism and is not associated with the specific immune response against the virus.


2011 ◽  
Vol 86 (4) ◽  
pp. 430-439 ◽  
Author(s):  
F. Tang ◽  
L. Xu ◽  
R. Yan ◽  
X. Song ◽  
X. Li

AbstractPlasmids expressing macrophage migration inhibitory factor (MIF) ofTrichinella spiralis(TsMIF), multi-cystatin-like domain protein (MCD-1) ofT. spiralis(TsMCD-1), or co-expressingTsMIF andTsMCD-1 were constructed with a pVAX1 vector. Their ability to generate a protective immune response againstT. spiralisinfection was evaluated in BALB/c mice. Groups of mice were immunized twice at 2-week intervals with 100 μg of recombinant plasmids pVAX1-Tsmif, pVAX1-Tsmcd-1or pVAX1-Tsmif-Tsmcd-1. Control animals were immunized with phosphate-buffered saline (PBS) or blank vector plasmid. Specific antibody levels (IgG, IgG1, IgG2a, IgG2b, IgM, IgA, IgE) against the recombinant proteinTsMIF-TsMCD-1, serum cytokines (interferon (IFN)-γ, interleukin (IL)-4, IL-5, transforming growth factor (TGF)-β1 and IL-17) and CD4+/CD8+T cells were monitored. Challenge infection was performed 2 weeks following the second immunization and worm burden was assayed at 35 days post-challenge. Vaccination with pVAX1-Tsmifinduced moderate serum IFN-γ and increases of CD4+and CD8+T cells, but no specific immunoglobulin antibody response. Vaccination with pVAX1-Tsmcd-1induced a predominant Th1 antibody (IgG2a and IgG2b) response and strong levels of serum IFN-γ, and increases of CD4+T cells. Importantly, co-expression ofTsMIF andTsMCD-1 in DNA immunization produced more serum IFN-γ and markedly enhanced CD4+and CD8+T cells than the single DNA vaccine of the two genes. Challenge infection demonstrated that immunization with pVAX1-Tsmif-Tsmcd-1reduced worm burdens (by 23.17%;P < 0.05).


1974 ◽  
Vol 140 (2) ◽  
pp. 356-369 ◽  
Author(s):  
Duane L. Peavy ◽  
Carl W. Pierce

The effects of soluble concanavalin A (Con A) or Con A-activated spleen cells on the generation of cytotoxic lymphocytes (CL) in mixed leukocyte cultures (MLC) were examined. Mitogenic concentrations of soluble Con A or small numbers of Con A-activated spleen cells substantially inhibited CL responses. The suppression was partial rather than absolute and was critically dependent upon the concentration and time of addition of soluble Con A or Con A-activated spleen cells to the MLC. Suppressive effects of Con-A activated spleen cells were mediated by T cells since suppressor cell activity was abrogated by treatment of spleen cells with anti-θ serum and complement before or after Con A activation. X irradiation of spleen cells before Con A treatment also abrogated generation of suppressor cell activity. After activation by Con A, however, the function of suppressor cells was radioresistant. Although the precise mechanism(s) of suppression is, as yet, unknown, the precursors of CL must be exposed to Con A-activated cells during the early phases of the immune response for suppression to occur. Kinetic studies revealed that suppression of CL responses was not due to a failure to initiate an immune response, but represented a response which developed initially, but subsequently aborted. The relevance of these observations to the concepts of T-cell-T-cell interaction and regulatory control of immune responses by T cells is discussed.


2021 ◽  
Vol 9 ◽  
Author(s):  
Julia Schiffner ◽  
Insa Backhaus ◽  
Jens Rimmele ◽  
Sören Schulz ◽  
Till Möhlenkamp ◽  
...  

Characterization of the naturally acquired B and T cell immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is important for the development of public health and vaccination strategies to manage the burden of COVID-19 disease. We conducted a prospective, cross-sectional analysis in COVID-19 recovered patients at various time points over a 10-month period in order to investigate how circulating antibody levels and interferon-gamma (IFN-γ) release by peripheral blood cells change over time following natural infection. From March 2020 till January 2021, we enrolled 412 adults mostly with mild or moderate disease course. At each study visit, subjects donated peripheral blood for testing of anti-SARS-CoV-2 IgG antibodies and IFN-γ release after SARS-CoV-2 S-protein stimulation. Anti-SARS-CoV-2 immunoglobulin G (IgG) antibodies were positive in 316 of 412 (76.7%) and borderline in 31 of 412 (7.5%) patients. Our confirmation assay for the presence of neutralizing antibodies was positive in 215 of 412 (52.2%) and borderline in 88 of 412 (21.4%) patients. Likewise, in 274 of 412 (66.5%) positive IFN-γ release and IgG antibodies were detected. With respect to time after infection, both IgG antibody levels and IFN-γ concentrations decreased by about half within 300 days. Statistically, production of IgG and IFN-γ were closely associated, but on an individual basis, we observed patients with high-antibody titres but low IFN-γ levels and vice versa. Our data suggest that immunological reaction is acquired in most individuals after natural infection with SARS-CoV-2 and is sustained in the majority of patients for at least 10 months after infection after a mild or moderate disease course. Since, so far, no robust marker for protection against COVID-19 exists, we recommend utilizing both, IgG and IFN-γ release for an individual assessment of the immunity status.


2021 ◽  
Author(s):  
Paul Naaber ◽  
Virge Jürjenson ◽  
Ainika Adamson ◽  
Epp Sepp ◽  
Liina Tserel ◽  
...  

AbstractBackgroundThe mRNA vaccines for SARS-CoV2 have proven highly effective and are currently used to vaccinate all age groups against COVID-19. Despite their high efficacy in clinical trials, there is limited data on the impact of age, sex, and side effects on vaccine-induced immune responses.MethodsWe here studied the development of SARS-CoV-2 Spike protein RBD domain antibodies after two doses of the Pfizer-BioNTech Comirnaty mRNA vaccine in 118 healthy volunteers and correlated their immune response with age, sex, and side effects reported after the vaccinations.FindingsOur findings show a robust immune response to the Spike protein’s RBD region after the first and the second vaccination dose. However, we also saw a decline of antibody levels at 6 weeks versus 1 week after the second dose, suggesting a waning of the immune response over time. Regardless of this, the antibody levels at 6 weeks after the second dose remained significantly higher than before the vaccination, after the first dose, or in COVID-19 convalescent individuals. We found a decreased vaccination efficacy but fewer adverse events in older individuals, and that mRNA vaccination is less efficient in older males whereas the detrimental impact of age on vaccination outcome is abolished in females at 6 weeks after the second dose.InterpretationThe Pfizer-BioNTech Comirnaty mRNA vaccine induces a strong immune response after two doses of vaccination but older individuals develop fewer side effects and decreased antibody levels at 6 weeks. The waning of anti-viral antibodies in particular in older male individuals suggests that both age and male sex act as risk factors in the immune response to the SARS-CoV-2 mRNA vaccine.FundingThe study was supported by the Centre of Excellence in Translational Genomics (EXCEGEN), and the Estonian Research Council grant PRG377 and SYNLAB Estonia.Research in contextEvidence before this studyThe first studies addressing the immune responses in older individuals after the single-dose administration of the SARS-CoV-2 mRNA vaccines have been published. We searched PubMed and medRxiv for publications on the immune response of SARS-CoV-2-mRNA vaccines, published in English, using the search terms “SARS-CoV-2”, “COVID-19”, “vaccine response”, “mRNA vaccine”, up to April 15th, 2021. To date, most mRNA vaccine response studies have not been peer-reviewed, and data on the role of age, sex and side effects on SARS-CoV-2-mRNA vaccines in real vaccination situations is limited. Some studies have found a weaker immune response in older individuals after the first dose and these have been measured at a relatively short period (within 1-2 weeks) after the first dose but little longer-term evidence exists on the postvaccination antibody persistence. Even less information is available on sex differences or correlations with mRNA vaccine side effects.Added value of this studyIn this study, we assessed the antibody response up to 6 weeks after the second dose of Pfizer-BioNTech Comirnaty mRNA vaccine in 118 individuals. Our findings show a strong initial immune response after the first dose and an even higher Spike RBD antibody levels at 1 week after the second dose, but these significantly declined at 6 weeks after the second dose. We also found a weaker immune response and faster waning of antibodies in older vaccinated individuals, which correlated with fewer side effects at the time of vaccinations. Furthermore, although overall female and male vaccinees responded similarly, we found that age-related waning of the vaccine-related antibodies was stronger amongst older males whereas in females the impact of age was lost at 6 weeks after the second dose.Implications of all the available evidenceNew mRNA vaccines are now applied worldwide as they have shown high efficacy in clinical trials. Our results show that two doses of Pfizer-BioNTech Comirnaty mRNA vaccine induce a strong antibody response to Spike RBD region but these high levels decline 1.5 months after the second dose in most of the vaccinated individuals. Nevertheless, even at 6 weeks after the second dose, they stay significantly higher than at prevaccination, after the first dose of vaccine, or in Covid-19 postinfection. These findings also implicate that fewer adverse effects may indicate lower antibody response after the vaccination and point to the need for more individualized vaccination protocols, in particular among older people.


2020 ◽  
Author(s):  
Hugh Adler ◽  
Esther L German ◽  
Elena Mitsi ◽  
Elissavet Nikolaou ◽  
Sherin Pojar ◽  
...  

Rationale: Pneumococcal colonisation is key to the pathogenesis of invasive disease, but is also immunogenic in young adults, protecting against re-colonisation. Colonisation is rarely detected in older adults, despite high rates of pneumococcal disease. Objectives: To establish experimental human pneumococcal colonisation in healthy adults aged 50-84 years, to measure the immune response to pneumococcal challenge, and to assess the protective effect of prior colonisation against autologous strain rechallenge. Methods: Sixty-four participants were inoculated with Streptococcus pneumoniae (serotype 6B, 80,000CFU in each nostril). Colonisation was determined by bacterial culture of nasal wash, serum anti-6B capsular IgG responses by ELISA, and anti-protein immune responses by multiplex electrochemiluminescence. Measurements and Main Results: Experimental colonisation was established in 39% of participants (25/64) with no adverse events. Colonisation occurred in 47% (9/19) of participants aged 50-59 compared with 21% (3/14) in those aged 70 years and older. Previous pneumococcal polysaccharide vaccination did not protect against colonisation. Colonisation did not confer serotype-specific immune boosting: GMT (95% CI) 2.7ug/mL (1.9-3.8) pre-challenge versus 3.0 (1.9-4.7) four weeks post-colonisation (p = 0.53). Furthermore, pneumococcal challenge without colonisation led to a drop in specific antibody levels from 2.8ug/mL (2.0-3.9) to 2.2ug/mL (1.6-3.0) post-challenge (p = 0.006). Anti-protein antibody levels increased following successful colonisation. Rechallenge with the same strain after a median of 8.5 months (IQR 6.7-10.1) led to recolonisation in 5/16 (31%). Conclusions: In older adults, experimental pneumococcal colonisation is feasible and safe, but demonstrates different immunological outcomes compared with younger adults in previous studies.


Sign in / Sign up

Export Citation Format

Share Document