scholarly journals Anti-Leptospira immunoglobulin profiling in mice reveals strain specific IgG and persistent IgM responses associated with virulence and renal colonization

2020 ◽  
Author(s):  
Frédérique Vernel-Pauillac ◽  
Gerald Murray ◽  
Ben Adler ◽  
Ivo G. Boneca ◽  
Catherine Werts
Keyword(s):  
Immune Response ◽  
Antibody Response ◽  
Post Infection ◽  
Severe Disease ◽  
Humoral Response ◽  
Antibody Responses ◽  
High Dose ◽  
Leptospira Interrogans ◽  
Homologous Challenge

AbstractLeptospira interrogans is a pathogenic spirochete responsible for leptospirosis, a neglected, zoonotic reemerging disease. Humans are sensitive hosts and may develop severe disease. Some animal species, such as rats and mice can become asymptomatic renal carriers. More than 350 leptospiral serovars have been identified, classified on the basis of the antibody response directed against the lipopolysaccharide (LPS). Similarly to whole inactivated bacteria used as human vaccines, this response is believed to confer only short-term, serogroup-specific protection. The immune response of hosts against leptospires has not been thoroughly studied and correlates of protection would be required to test vaccine candidates. In this work, we studied the immunoglobulin (Ig) profiles in mice infected with L. interrogans over time to determine whether this humoral response confers long-term protection after homologous challenge six months post-infection.Groups of mice were injected intraperitoneally with 2×107 leptospires of one of three pathogenic serovars (Manilae, Copenhageni or Icterohaemorrhagiae), attenuated mutants or heat-killed bacteria. Leptospira-specific immunoglobulin (IgA, IgM, IgG and 4 subclasses) produced in the first weeks up to 6 months post-infection were measured by ELISA. Strikingly, we found sustained high levels of IgM in mice infected with the pathogenic Manilae and Copenhageni strains, both colonizing the kidney. In contrast, the Icterohaemorrhagiae strain did not lead to kidney colonization, even at high dose, and triggered a classical IgM response that peaked at day 8 post-infection and disappeared. The virulent Manilae and Copenhageni serovars elicited high levels and similar profiles of IgG subclasses in contrast to Icterohaemorrhagiae strains that stimulated weaker antibody responses. Inactivated heat-killed Manilae strains elicited very low responses. However, all mice pre-injected with leptospires challenged with high doses of homologous bacteria did not develop acute leptospirosis, and all antibody responses were boosted after challenge. Furthermore, we showed that 2 months post challenge, mice pre-infected with the M895 Manilae LPS mutant or heat-killed bacterin were completely protected against renal colonization. In conclusion, we observed a sustained IgM response potentially associated with chronic leptospiral renal infection. We also demonstrated in mice different profiles of protective antibody response after L. interrogans infection, depending on the serovar and virulence of strains.Author summaryLeptospira interrogans is a pathogenic spirochete responsible for leptospirosis, a neglected zoonotic reemerging disease. The immune response of hosts against these bacteria has not been thoroughly studied. Here, we studied over 6 months the immunoglobulin (Ig) profiles in mice infected with L. interrogans and determined whether this humoral response confers long-term protection after homologous challenge six months after primary infection. Groups of mice were infected intraperitoneally with 2×107 bacteria of one of three different pathogenic serovars (Manilae, Copenhageni and Icterohaemorrhagiae) and some corresponding attenuated avirulent mutants. We measured by ELISA each type of Leptospira-specific Ig (IgA, IgM, IgG and 4 subclasses) produced in the first weeks up to 6 months post-infection. We showed different profiles of antibody response after L. interrogans challenge in mice, depending on the serovar and virulence of strains. However, all infected mice, including the ones harboring low antibody levels, like mice vaccinated with an inactivated, heat-killed strain, were protected against leptospirosis after challenge. Notably, we also showed an unusual sustained IgM response associated with chronic leptospiral colonization. Altogether, this long-term immune protection is different from what is known in humans and warrants further investigation.

scholarly journals Anti-Leptospira immunoglobulin profiling in mice reveals strain specific IgG and persistent IgM responses associated with virulence and renal colonization

2021 ◽  
Vol 15 (3) ◽  
pp. e0008970
Author(s):  
Frédérique Vernel-Pauillac ◽  
Gerald L. Murray ◽  
Ben Adler ◽  
Ivo G. Boneca ◽  
Catherine Werts
Keyword(s):  
Post Infection ◽  
Severe Disease ◽  
Humoral Response ◽  
Antibody Responses ◽  
High Dose ◽  
Specific Igg ◽  
High Doses ◽  
Rats And Mice ◽  
Renal Infection

Leptospira interrogans is a pathogenic spirochete responsible for leptospirosis, a neglected, zoonotic reemerging disease. Humans are sensitive hosts and may develop severe disease. Some animal species, such as rats and mice can become asymptomatic renal carriers. More than 350 leptospiral serovars have been identified, classified on the basis of the antibody response directed against the lipopolysaccharide (LPS). Similarly to whole inactivated bacteria used as human vaccines, this response is believed to confer only short-term, serogroup-specific protection. The immune response of hosts against leptospires has not been thoroughly studied, which complicates the testing of vaccine candidates. In this work, we studied the immunoglobulin (Ig) profiles in mice infected with L. interrogans over time to determine whether this humoral response confers long-term protection after homologous challenge six months post-infection. Groups of mice were injected intraperitoneally with 2×107 leptospires of one of three pathogenic serovars (Manilae, Copenhageni or Icterohaemorrhagiae), attenuated mutants or heat-killed bacteria. Leptospira-specific immunoglobulin (IgA, IgM, IgG and 4 subclasses) produced in the first weeks up to 6 months post-infection were measured by ELISA. Strikingly, we found sustained high levels of IgM in mice infected with the pathogenic Manilae and Copenhageni strains, both colonizing the kidney. In contrast, the Icterohaemorrhagiae strain did not lead to kidney colonization, even at high dose, and triggered a classical IgM response that peaked at day 8 post-infection and disappeared. The virulent Manilae and Copenhageni serovars elicited high levels and similar profiles of IgG subclasses in contrast to Icterohaemorrhagiae strains that stimulated weaker antibody responses. Inactivated heat-killed Manilae strains elicited very low responses. However, all mice pre-injected with leptospires challenged with high doses of homologous bacteria did not develop acute leptospirosis, and all antibody responses were boosted after challenge. Furthermore, we showed that 2 months post challenge, mice pre-infected with the attenuated M895 Manilae LPS mutant or heat-killed bacterin were completely protected against renal colonization. In conclusion, we observed a sustained IgM response potentially associated with chronic leptospiral renal infection. We also demonstrated in mice different profiles of protective and cross-reactive antibodies after L. interrogans infection, depending on the serovar and virulence of strains.

scholarly journals Defining Antibody Seroprevalence and Duration of Humoral Responses to SARS-CoV-2 Infection and/or Vaccination in a Greek Community

2021 ◽  
Vol 19 (1) ◽  
pp. 407
Author(s):  
Ourania S. Kotsiou ◽  
Dimitrios Papagiannis ◽  
Evangelos C. Fradelos ◽  
Dimitra I. Siachpazidou ◽  
Garifallia Perlepe ◽  
...  
Keyword(s):  
Immune Response ◽  
Antibody Response ◽  
Severe Disease ◽  
Vaccination Status ◽  
Antibody Responses ◽  
Antibody Testing ◽  
Mild Disease ◽  
Antibody Titers ◽  
Humoral Responses ◽  
Pandemic Wave

Background: In this work we aimed to evaluate antibody-response longevity to SARS-CoV-2 infection and/or vaccination in one of the Greek communities that was worst hit by the pandemic, Deskati, five months after a previous serosurveillance and nine months after the pandemic wave initiation (October 2020). Methods: The SARS-CoV-2 IgG II Quant method (Architect, Abbott, IL, USA) was used for antibody testing. Results: A total of 69 subjects, who previously tested positive or negative for COVID-19 antibodies, participated in the study. We found that 48% of participants turned positive due to vaccination and 27% of participants were both previously infected and vaccinated. All previously infected participants retained antibodies to the virus, irrespective of their vaccination status. The antibody titers were significantly higher in previously infected participants that had been vaccinated than those who were unvaccinated and in those that had been previously hospitalized for COVID-19 than those with mild disease. Conclusions: Antibody responses to SARS-CoV-2 infection were maintained nine months after the pandemic. Vaccination alone had generated an immune response in almost half of the population. Higher antibody titers were found in the case of vaccination in previously infected subjects and especially in those with severe disease leading to hospitalization

scholarly journals Dynamics of the Humoral Immune Response to a Prime-Boost Ebola Vaccine: Quantification and Sources of Variation

2019 ◽  
Vol 93 (18) ◽  
Author(s):  
Chloé Pasin ◽  
Irene Balelli ◽  
Thierry Van Effelterre ◽  
Viki Bockstal ◽  
Laura Solforosi ◽  
...  
Keyword(s):  
Immune Response ◽  
Antibody Response ◽  
Humoral Immune Response ◽  
Phase 1 ◽  
Humoral Response ◽  
Enzyme Linked Immunosorbent Assay ◽  
Phase 1 Trials ◽  
Humoral Immune ◽  
Boost Immunization

ABSTRACT The Ebola vaccine based on Ad26.ZEBOV/MVA-BN-Filo prime-boost regimens is being evaluated in multiple clinical trials. The long-term immune response to the vaccine is unknown, including factors associated with the response and variability around the response. We analyzed data from three phase 1 trials performed by the EBOVAC1 Consortium in four countries: the United Kingdom, Kenya, Tanzania, and Uganda. Participants were randomized into four groups based on the interval between prime and boost immunizations (28 or 56 days) and the sequence in which Ad26.ZEBOV and MVA-BN-Filo were administered. Consecutive enzyme-linked immunosorbent assay (ELISA) measurements of the IgG binding antibody concentrations against the Kikwit glycoprotein (GP) were available for 177 participants to assess the humoral immune response up to 1 year postprime. Using a mathematical model for the dynamics of the humoral response, from 7 days after the boost immunization up to 1 year after the prime immunization, we estimated the durability of the antibody response and the influence of different factors on the dynamics of the humoral response. Ordinary differential equations (ODEs) described the dynamics of antibody response and two populations of antibody-secreting cells (ASCs), short-lived (SL) and long-lived (LL). Parameters of the ODEs were estimated using a population approach. We estimated that half of the LL ASCs could persist for at least 5 years. The vaccine regimen significantly affected the SL ASCs and the antibody peak but not the long-term response. The LL ASC compartment dynamics differed significantly by geographic regions analyzed, with a higher long-term antibody persistence in European subjects. These differences could not be explained by the observed differences in cellular immune response. IMPORTANCE With no available licensed vaccines or therapies, the West African Ebola virus disease epidemic of 2014 to 2016 caused 11,310 deaths. Following this outbreak, the development of vaccines has been accelerated. Combining different vector-based vaccines as heterologous regimens could induce a durable immune response, assessed through antibody concentrations. Based on data from phase 1 trials in East Africa and Europe, the dynamics of the humoral immune response from 7 days after the boost immunization onwards were modeled to estimate the durability of the response and understand its variability. Antibody production is maintained by a population of long-lived cells. Estimation suggests that half of these cells can persist for at least 5 years in humans. Differences in prime-boost vaccine regimens affect only the short-term immune response. Geographical differences in long-lived cell dynamics were inferred, with higher long-term antibody concentrations induced in European participants.

scholarly journals Long-term maternal effect on offspring immune response in song sparrows Melospiza melodia

2006 ◽  
Vol 2 (4) ◽  
pp. 573-576 ◽  
Author(s):  
Jane M Reid ◽  
Peter Arcese ◽  
Lukas F Keller ◽  
Dennis Hasselquist
Keyword(s):  
Immune Response ◽  
Time Scales ◽  
Parasitic Infection ◽  
Antibody Responses ◽  
Melospiza Melodia ◽  
Long Term Effects ◽  
Free Living ◽  
Humoral Immune ◽  
Song Sparrows

Knowledge of the causes of variation in host immunity to parasitic infection and the time-scales over which variation persists, is integral to predicting the evolutionary and epidemiological consequences of host–parasite interactions. It is clear that offspring immunity can be influenced by parental immune experience, for example, reflecting transfer of antibodies from mothers to young offspring. However, it is less clear whether such parental effects persist or have functional consequences over longer time-scales, linking a parent's previous immune experience to future immune responsiveness in fully grown offspring. We used free-living song sparrows ( Melospiza melodia ) to quantify long-term effects of parental immune experience on offspring immune response. We experimentally vaccinated parents with a novel antigen and tested whether parental vaccination influenced the humoral antibody response mounted by fully grown offspring hatched the following year. Parental vaccination did not influence offspring baseline antibody titres. However, offspring of vaccinated mothers mounted substantially stronger antibody responses than offspring of unvaccinated mothers. Antibody responses did not differ between offspring of vaccinated and unvaccinated fathers. These data demonstrate substantial long-term effects of maternal immune experience on the humoral immune response of fully grown offspring in free-living birds.

scholarly journals Short- and long-term humoral immune response against Yersinia pestis in plague patients, Madagascar

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Voahangy Andrianaivoarimanana ◽  
Alice Lantoniaina Iharisoa ◽  
Lila Rahalison ◽  
Marie Laurette Ralimanantsoa ◽  
Maherisoa Ratsitorahina ◽  
...  
Keyword(s):  
Immune Response ◽  
Antibody Response ◽  
Yersinia Pestis ◽  
Disease Onset ◽  
Seroprevalence Rate ◽  
Humoral Immune ◽  
Long Term Study ◽  
Exposed Population ◽  
Short And Long Term

Abstract Background Plague, a fatal disease caused by the bacillus, Yersinia pestis, still affects resources-limited countries. Information on antibody response to plague infection in human is scarce. Anti-F1 Ig G are among the known protective antibodies against Y. pestis infection. As a vaccine preventable disease, knowledge on antibody response is valuable for the development of an effective vaccine to reduce infection rate among exposed population in plague-endemic regions. In this study, we aim to describe short and long-term humoral immune responses against Y. pestis in plague-confirmed patients from Madagascar, the most affected country in the world. Methods Bubonic (BP) and pneumonic plague (PP) patients were recruited from plague- endemic foci in the central highlands of Madagascar between 2005 and 2017. For short-term follow-up, 6 suspected patients were enrolled and prospectively investigated for kinetics of the anti-F1 IgG response, whereas the persistence of antibodies was retrospectively studied in 71 confirmed convalescent patients, using an ELISA which was validated for the detection of plague in human blood samples in Madagascar. Results Similarly to previous findings, anti-F1 IgG rose quickly during the first week after disease onset and increased up to day 30. In the long-term study, 56% of confirmed cases remained seropositive, amongst which 60 and 40% could be considered as high- and low-antibody responders, respectively. Antibodies persisted for several years and up to 14.8 years for one individual. Antibody titers decreased over time but there was no correlation between titer and time elapsed between the disease onset and serum sampling. In addition, the seroprevalence rate was not significantly different between gender (P = 0.65) nor age (P = 0.096). Conclusion Our study highlighted that the circulating antibody response to F1 antigen, which is specific to Y. pestis, may be attributable to individual immune responsiveness. The finding that a circulating anti-F1 antibody titer could persist for more than a decade in both BP and PP recovered patients, suggests its probable involvement in patients’ protection. However, complementary studies including analyses of the cellular immune response to Y. pestis are required for the better understanding of long-lasting protection and development of a potential vaccine against plague.

scholarly journals REGULATION OF ANTIBODY RESPONSE BY CELLS EXPRESSING HISTAMINE RECEPTORS

1972 ◽  
Vol 136 (5) ◽  
pp. 1302-1307 ◽  
Author(s):  
G. M. Shearer ◽  
Kenneth L. Melmon ◽  
Yacob Weinstein ◽  
Michael Sela
Keyword(s):  
Immune Response ◽  
Antibody Response ◽  
Serum Albumin ◽  
Sheep Erythrocyte ◽  
Antibody Responses ◽  
Rabbit Serum ◽  
Spleen Cells ◽  
Surface Receptors ◽  
Cell Responses ◽  
A Cell

Spleen cells from immunized and unimmunized mice were either passed over histamine-rabbit serum albumin-Sepharose columns or rabbit serum albumin-Sepharose control columns. The immune response potential of 5 x 106 cells excluded from the two columns were compared with each other, and with an equal number of unfiltered cells by injection of the cell suspensions mixed with sheep erythrocytes into irradiated, syngeneic recipients. The direct and indirect anti-sheep erythrocyte plaque-forming cell responses generated by the cells passed over the histamine-bead column were significantly greater than the responses resulting from the inocula of unfiltered cells or cells passed over control columns. These results indicate the existence of a cell population expressing surface receptors for histamine, which functions to regulate antibody responses.

Experimental oral and ocularEncephalitozoon cuniculiinfection in rabbits

Parasitology ◽  
2010 ◽  
Vol 137 (12) ◽  
pp. 1749-1757 ◽  
Author(s):  
E. JEKLOVA ◽  
L. LEVA ◽  
K. KOVARCIK ◽  
J. MATIASOVIC ◽  
V. KUMMER ◽  
...  
Keyword(s):  
Antibody Response ◽  
Experimental Infection ◽  
Post Infection ◽  
Clinical Signs ◽  
High Dose ◽  
Cell Mediated Immunity ◽  
Specific Cell ◽  
Immunological Responses ◽  
Obligate Intracellular Pathogen ◽  
Dose Dependent

SUMMARYEncephalitozoon cuniculiis an obligate intracellular pathogen that has a wide host distribution, but primarily affects rabbits. The aim of this study was to characterize both the cell-mediated and the antibody response in rabbits after experimental infection using 2 different infection routes: oral and ocular. SPF rabbits were infected with low (103spores) and high (107spores) infection doses. Monitored parameters included clinical signs, detection of spores in urine, antibody response detected with ELISA, and cell-mediated immunity detected by antigen-driven lymphocyte proliferation. At week 13 post-infection, half of the rabbits in each group were suppressed by intramuscular administration of dexamethasone. At week 18 post-infection, animals were euthanized. Clinical signs were mild with exacerbation after immunosuppression. Spores in urine and antigen-specific cell-mediated immunity were detected from weeks 5 and 4 post-infection, respectively. Specific IgM was detected 1 week after infection, and IgG antibodies followed 1 week later in rabbits infected with the high dose. Immunological responses were dose dependent. The authors can conclude that both oral and ocular experimental infection withE. cuniculiresulted in an immune response of the infected animals. Rabbits could be used as an experimental model for the study of ocular microsporidiosis.

scholarly journals Characterization of a Permissive Epitope Insertion Site in Adenovirus Hexon

2006 ◽  
Vol 80 (11) ◽  
pp. 5361-5370 ◽  
Author(s):  
Michael J. McConnell ◽  
Xavier Danthinne ◽  
Michael J. Imperiale
Keyword(s):  
Immune Response ◽  
Antibody Response ◽  
B Cell ◽  
Protective Antigen ◽  
Insertion Site ◽  
Cell Epitope ◽  
Hypervariable Region ◽  
Humoral Response ◽  
Virus Infectivity ◽  
Robust Immune Response

ABSTRACT A robust immune response is generated against components of the adenovirus capsid. In particular, a potent and long-lived humoral response is elicited against the hexon protein. This is due to the efficient presentation of adenovirus capsid proteins to CD4+ T cells by antigen-presenting cells, in addition to the highly repetitive structure of the adenovirus capsids, which can efficiently stimulate B-cell proliferation. In the present study, we take advantage of this immune response by inserting epitopes against which an antibody response is desired into the adenovirus hexon. We use a B-cell epitope from Bacillus anthracis protective antigen (PA) as a model antigen to characterize hypervariable region 5 (HVR5) of hexon as a site for peptide insertion. We demonstrate that HVR5 can accommodate a peptide of up to 36 amino acids without adversely affecting virus infectivity, growth, or stability. Viruses containing chimeric hexons elicited antibodies against PA in mice, with total immunoglobulin G (IgG) titers reaching approximately 1 × 103 after two injections. The antibody response contained both IgG1 and IgG2a subtypes, suggesting that Th1 and Th2 immunity had been stimulated. Coinjection of wild-type adenovirus and a synthetic peptide from PA produced no detectable antibodies, indicating that incorporation of the epitope into the capsid was crucial for immune stimulation. Together, these results indicate that the adenovirus capsid is an efficient vehicle for presenting B-cell epitopes to the immune system, making this a useful approach for the design of epitope-based vaccines.

scholarly journals Depletion of Complement Has Distinct Effects on the Primary and Secondary Antibody Responses to a Conjugate of Pneumococcal Serotype 14 Capsular Polysaccharide and a T-Cell-Dependent Protein Carrier

2005 ◽  
Vol 73 (1) ◽  
pp. 277-286 ◽  
Author(s):  
Samuel T. Test ◽  
Joyce K. Mitsuyoshi ◽  
Yong Hu
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Antibody Response ◽  
Complement Activation ◽  
Capsular Polysaccharide ◽  
Antibody Responses ◽  
Primary Immunization ◽  
Protein Carrier ◽  
Dependent Protein

ABSTRACT Complement activation plays a critical role in the immune response to T-cell-dependent and T-cell-independent antigens. However, the effect of conjugation of T-cell-dependent protein carriers to T-cell-independent type 2 antigens on the requirement for complement in the humoral immune response to such antigens remains unknown. We studied the role of complement activation on the antibody response of BALB/c mice immunized with the T-cell-independent type 2 antigen serotype 14 pneumococcal capsular polysaccharide (PPS14), either in unmodified form or conjugated to ovalbumin (OVA). In mice immunized with either PPS14 or PPS14-OVA, depletion of endogenous complement at the time of primary immunization by treatment with cobra venom factor (CVF) diminished serum anti-PPS14 concentrations after primary immunization but enhanced antibody responses after secondary immunization. The secondary immunoglobulin G (IgG) anti-PPS14 antibody response after immunization with PPS14-OVA was especially enhanced by complement depletion, was observed at doses as low as 0.2 μg of antigen, and was maximal when CVF was administered within 2 days of immunization. The avidity and opsonophagocytic functions of IgG anti-PPS14 antibodies were comparable in mice immunized with PPS14-OVA with or without complement depletion. Serum anti-PPS14 antibody concentrations were near normal, and the enhancing effects of CVF treatment on the secondary anti-PPS14 antibody response were also apparent in splenectomized mice immunized with PPS14-OVA. These results demonstrate that complement activation can have distinct effects on the primary and secondary antibody responses to a T-cell-independent type 2 antigen, either unmodified or conjugated to a T-cell-dependent protein carrier. These differences should be taken into consideration when using complement to modulate the immune response to vaccines.

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