scholarly journals Influence of Intravenous Anesthesia on Mucosal and Systemic Antibody Responses to Nasal Vaccines

2002 ◽  
Vol 70 (10) ◽  
pp. 5479-5484 ◽  
Author(s):  
Libuse Janakova ◽  
Hilde Bakke ◽  
Inger Lise Haugen ◽  
Aud K. H. Berstad ◽  
E. Arne Høiby ◽  
...  

ABSTRACT Inhalation of antigens may stimulate the immune system by way of the upper as well as the lower airways. We have shown that at least 1,000 times more live pneumococci were recovered from pulmonary tissue after being presented as drops of a liquid suspension onto the nares of anesthetized mice compared to the number of bacteria recovered from animals that were not anesthetized in the course of the challenge. Mice that were similarly immunized intranasally by inhalation of three different nonreplicating particulate vaccine formulations, i.e., a meningococcal outer membrane vesicle (OMV) vaccine, a formalin-inactivated whole-virus influenza (INV) vaccine, and the INV vaccine with OMVs as a mucosal adjuvant, during general intravenous anesthesia developed concentrations of vaccine-specific serum immunoglobulin G (IgG) antibodies that were four to nine times higher than in mice that were fully awake during immunizations. The concentrations of IgA antibodies in serum were also higher in anesthetized than in nonanesthetized mice and correlated positively with the corresponding levels of serum IgG antibodies in the anesthetized but not in the nonanesthetized mice. In saliva and feces, however, the concentrations of IgA antibodies were equally high whether or not the animals were dormant during immunizations. The results indicate that intrapulmonary antigen presentation, as a part of an intranasal immunization strategy, is of importance for systemic but not for mucosal antibody responses. A major portion of IgA antibodies in serum may thus be derived from nonmucosal sites.

2005 ◽  
Vol 79 (20) ◽  
pp. 13186-13189 ◽  
Author(s):  
James E. Cummins ◽  
Roumiana S. Boneva ◽  
William M. Switzer ◽  
Logan L. Christensen ◽  
Paul Sandstrom ◽  
...  

ABSTRACT Simian foamy virus (SFV) infection and the subsequent immune response are not well characterized. Blood plasma, saliva, and urine were obtained from four humans and nine chimpanzees persistently infected with chimpanzee-type SFV for an unknown length of time. SFV-specific immunoglobulin G (IgG) antibodies, but not IgA antibodies, against the Gag and Bet proteins were detected, by Western blotting, in all sample types from infected humans and chimpanzees. Overall, chimpanzee samples had higher anti-SFV IgG titers than humans. These results provide a first comparative evaluation of SFV-specific host mucosal humoral immunity in infected humans and chimpanzees that is characterized by a predominant IgG response and a virtually absent IgA response.


2005 ◽  
Vol 73 (8) ◽  
pp. 5031-5038 ◽  
Author(s):  
David R. Shoemaker ◽  
Nancy B. Saunders ◽  
Brenda L. Brandt ◽  
E. Ellen Moran ◽  
Andrew D. LaClair ◽  
...  

ABSTRACT We have previously shown that intranasal immunization of mice with meningococcal native outer membrane vesicles (NOMV) induces both a good local mucosal antibody response and a good systemic bactericidal antibody response. However, in the intranasal mouse model, some of the NOMV entered the lung and caused an acute granulocytic response. We therefore developed an alternate animal model using the rabbit. This model reduces the probability of lung involvement and more closely mimics intranasal immunization of humans. Rabbits immunized intranasally with doses of 100 μg of NOMV in 0.5 ml of saline developed serum bactericidal antibody levels comparable to those of rabbits immunized intramuscularly with 25-μg doses, particularly when the primary intranasal immunization was given daily for 3 days. Intranasal immunization also induced a local mucosal response as evidenced by immunoglobulin A antibody in saliva, nasal washes, and lung lavage fluids. NOMV from a capsule-deficient mutant induced higher serum bactericidal antibody responses than NOMV from the encapsulated parent. Meningococcal NOMV could be administered intranasally at 400 μg with no pyrogenic activity, but as little as 0.03 μg/kg of body weight administered intravenously or 25 μg administered intramuscularly induced a pyrogenic response. These data indicate that the rabbit is a useful model for preclinical testing of intranasal meningococcal NOMV vaccines, and this immunization regimen produces a safe and substantial systemic and local mucosal antibody response.


2021 ◽  
Author(s):  
Bernadette Crescenzo-Chaigne ◽  
Sylvie Behillil ◽  
Vincent Enouf ◽  
Nicolas Escriou ◽  
Stephane Petres ◽  
...  

AbstractBackgroundThe systemic antibody responses to SARS-CoV-2 in COVID-19 patients has been extensively studied. However, much less is known about the mucosal responses in the upper airways at the site of initial SARS-CoV-2 replication. Local antibody responses in the nasopharyngeal epithelium, that are likely to determine the course of infection, have not been analysed so far nor their correlation with antibody responses in serum.MethodsThe IgG and IgA antibody responses were analysed in the plasma as well as in nasopharyngeal swabs (NPS) from the first four COVID-19 patients confirmed by RT-qPCR in France. Two were pauci-symptomatic while two developed severe disease. Taking advantage of a comprehensive series of plasma and nasopharyngeal samples, we characterized their antibody profiles from the second week post symptoms onset, by using an in-house ELISA to detect anti-SARS-CoV-2 Nucleoprotein (N) IgG and IgA.ResultsAnti-N IgG and IgA antibodies were detected in the NPS of severe patients. Overall, the levels of IgA and IgG antibodies in plasma and NPS appeared specific to each patient.ConclusionsAnti-N IgG and IgA antibodies are detected in NPS, and their levels are related to antibody levels in plasma. The two patients with severe disease exhibited different antibody profiles that may reflect different disease outcome. For the pauci-symptomatic patients, one showed a low anti-N IgG and IgA response in the plasma only, while the other one did not exhibit overt serological response.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ariel Munitz ◽  
L. Edry-Botzer ◽  
M. Itan ◽  
R. Tur-Kaspa ◽  
D. Dicker ◽  
...  

AbstractDespite ongoing efforts to characterize the host response toward SARS-CoV-2, a major gap in our knowledge still exists regarding the magnitude and duration of the humoral response. Analysis of the antibody response in mild versus moderate/severe patients, using our new developed quantitative electrochemiluminescent assay for detecting IgM/IgA/IgG antibodies toward SARS-CoV-2 antigens, revealed a rapid onset of IgG/IgA antibodies, specifically in moderate/severe patients. IgM antibodies against the viral receptor binding domain, but not against nucleocapsid protein, were detected at early stages of the disease. Furthermore, we observed a marked reduction in IgM/IgA antibodies over-time. Adapting our assay for ACE2 binding-competition, demonstrated that the presence of potentially neutralizing antibodies is corelated with IgG/IgA. Finally, analysis of the cytokine profile in COVID-19 patients revealed unique correlation of an IL-12p70/IL33 and IgG seroconversion, which correlated with disease severity. In summary, our comprehensive analysis has major implications on the understanding and monitoring of SARS-CoV-2 infections.


Author(s):  
Claudia Seikrit ◽  
Oliver Pabst

AbstractAntibodies are key elements of protective immunity. In the mucosal immune system in particular, secretory immunoglobulin A (SIgA), the most abundantly produced antibody isotype, protects against infections, shields the mucosal surface from toxins and environmental factors, and regulates immune homeostasis and a peaceful coexistence with our microbiota. However, the dark side of IgA biology promotes the formation of immune complexes and provokes pathologies, e.g., IgA nephropathy (IgAN). The precise mechanisms of how IgA responses become deregulated and pathogenic in IgAN remain unresolved. Yet, as the field of microbiota research moved into the limelight, our basic understanding of IgA biology has been taking a leap forward. Here, we discuss the structure of IgA, the anatomical and cellular foundation of mucosal antibody responses, and current concepts of how we envision the interaction of SIgA and the microbiota. We center on key concepts in the field while taking account of both historic findings and exciting new observations to provide a comprehensive groundwork for the understanding of IgA biology from the perspective of a mucosal immunologist.


Immunity ◽  
2010 ◽  
Vol 33 (4) ◽  
pp. 479-491 ◽  
Author(s):  
Kang Chen ◽  
Andrea Cerutti

1993 ◽  
Vol 35 (4) ◽  
pp. 361-365 ◽  
Author(s):  
Cláudio L. Rossi ◽  
Emilia E. H. Takahashi ◽  
Cláudia D. Partel ◽  
Lívia G.V.L. Teodoro ◽  
Luiz J. da Silva

Total serum IgE, and Strongyloides - specific IgG and IgA antibodies were studied in 27 patients with parasitologically proven strongyloidiasis. Clinical manifestations in this case series were investigated by a restrospective study of the patient's records. Total serum IgE levels were elevated (greater than 250 IU/ml) in 59% of the patients (mean concentration = 1364 IU/ml). Parasite - specific IgG and IgA antibodies were detected by ELISA in the serum of 23 (85.2%) and 21 (77.8%) patients, respectively. Elevated serum IgE and clinical manifestations were not useful indexes of the presence of strongyloidiasis. On the other hand, our results support the view that serologic tests, particularly ELISA for detecting Strongyloides - specific IgG antibodies, can be usefully exploited for diagnostic purposes in strongyloidiasis.


2018 ◽  
Vol 87 (2) ◽  
Author(s):  
Patrick M. Meyer Sauteur ◽  
Adrianus C. J. M. de Bruijn ◽  
Catarina Graça ◽  
Anne P. Tio-Gillen ◽  
Silvia C. Estevão ◽  
...  

ABSTRACTAntibody responses toMycoplasma pneumoniaecorrelate with pulmonaryM. pneumoniaeclearance. However,M. pneumoniae-specific IgG antibodies can cross-react with the myelin glycolipid galactocerebroside (GalC) and cause neurological disorders. We assessed whether antiglycolipid antibody formation is part of the physiological immune response toM. pneumoniae. We show that antibodies againstM. pneumoniaeproteins and glycolipids arise in serum ofM. pneumoniae-infected children and mice. Although antibodies toM. pneumoniaeglycolipids were mainly IgG, anti-GalC antibodies were only IgM. B-1a cells, shown to aid in protection against pathogen-derived glycolipids, are lacking in Bruton tyrosine kinase (Btk)-deficient mice.M. pneumoniae-infected Btk-deficient mice developedM. pneumoniae-specific IgG responses toM. pneumoniaeproteins but not toM. pneumoniaeglycolipids, including GalC. The equal recovery fromM. pneumoniaeinfection in Btk-deficient and wild-type mice suggests that pulmonaryM. pneumoniaeclearance is predominantly mediated by IgG reactive withM. pneumoniaeproteins and thatM. pneumoniaeglycolipid-specific IgG or IgM is not essential. These data will guide the development ofM. pneumoniae-targeting vaccines that avoid the induction of neurotoxic antibodies.


mBio ◽  
2016 ◽  
Vol 7 (5) ◽  
Author(s):  
Caitlin E. Mullarkey ◽  
Mark J. Bailey ◽  
Diana A. Golubeva ◽  
Gene S. Tan ◽  
Raffael Nachbagauer ◽  
...  

ABSTRACTBroadly neutralizing antibodies that recognize the conserved hemagglutinin (HA) stalk have emerged as exciting new biotherapeutic tools to combat seasonal and pandemic influenza viruses. Our general understanding of the mechanisms by which stalk-specific antibodies achieve protection is rapidly evolving. It has recently been demonstrated that broadly neutralizing HA stalk-specific IgG antibodies require Fc-Fcγ receptor (FcγR) interactions for optimal protectionin vivo. Here we examine the neutrophil effector functions induced by stalk-specific antibodies. As the most abundant subset of blood leukocytes, neutrophils represent a critical innate effector cell population and serve an instrumental role in orchestrating downstream adaptive responses to influenza virus infection. Yet, the interplay of HA stalk-specific IgG, Fc-FcγR engagement, and neutrophils has remained largely uncharacterized. Using anin vitroassay to detect the production of reactive oxygen species (ROS), we show that human and mouse monoclonal HA stalk-specific IgG antibodies are able to induce the production of ROS by neutrophils, while HA head-specific antibodies do not. Furthermore, our results indicate that the production of ROS is dependent on Fc receptor (FcR) engagement and phagocytosis. We went on to assess the ability of monoclonal HA stalk-specific IgA antibodies to induce ROS. Consistent with our findings for monoclonal IgGs, only HA stalk-specific IgA antibodies elicited ROS production by neutrophils. This induction is dependent on the engagement of FcαR1. Taken together, our findings describe a novel FcR-dependent effector function induced by HA stalk-specific IgG and IgA antibodies, and importantly, our studies shed light on the mechanisms by which HA stalk-specific antibodies achieve protection.IMPORTANCEThe present study provides evidence that broadly neutralizing HA stalk-specific antibodies induce downstream Fc-mediated neutrophil effector functions. In addition to their ability to neutralize, this class of antibodies has been shown to rely on Fc-Fc receptor interactions for optimal protectionin vivo. Curiously, neutralizing antibodies that bind the HA head domain do not require such interactions. Our findings build on these previous observations and provide a more complete picture of the relationship between stalk-specific antibodies and cells of the innate immune compartment. Furthermore, our data suggest that the ability of HA stalk-specific antibodies to mediate Fc-Fc receptor engagement is epitope dependent. Overall, this work will inform the rational design of improved influenza virus vaccines and therapeutics.


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