scholarly journals Maternal transfer of IgA and IgG SARS-CoV-2 specific antibodies transplacentally and via breastfeeding

Author(s):  
Mohammad M. Sajadi ◽  
Narjes Shokatpour ◽  
Allison Bathula ◽  
Zahra Tehrani ◽  
Allison Lankford ◽  
...  

Although there have been many studies on antibody responses to SARS-CoV-2 in breastmilk, very few have looked at the fate of these in the baby. We carried out a study in 22 mother/baby pairs (mothers who breastfed and who were SARS-CoV-2 vaccinated before or after delivery) looking at mother blood, mother milk, baby blood, baby nose, and baby stool. Breastfed infants only acquired systemic anti-SARS-CoV-2 IgG antibodies if their mothers were vaccinated antepartum. None of the infants had SARS-CoV-2-specific IgA in the blood, but surprisingly, half of the infants in the Antepartum group had high titer SARS-CoV-2-specific IgA in the nose that exceeded titers found in breastmilk. Vaccination antepartum followed by breastfeeding appears to be the best way to provide systemic and local anti-SARS-CoV-2 antibodies for infants.

2007 ◽  
Vol 14 (8) ◽  
pp. 931-936 ◽  
Author(s):  
Monica E. Embers ◽  
Mary B. Jacobs ◽  
Barbara J. B. Johnson ◽  
Mario T. Philipp

ABSTRACTLyme borreliosis (LB) is a disease for which antibody-based detection assays are often required for diagnosis. The variable surface molecule VlsE and IR6, one of its invariable regions, are commonly targeted by the antibody response in infected individuals. A series of enzyme-linked immunosorbent assays was performed to comparatively examine the antibody responses of North American LB patients (n= 37) to VlsE and invariable segments of this molecule. Both immunoglobulin M (IgM) and IgG responses to full-length VlsE and to peptides reproducing invariable regions 2, 4, and 6, as well as the invariable domains at the amino and carboxyl termini of VlsE, were assessed. The proportions and specificities of reactivity to the invariable segments were tested by using cognate peptides as competitors for VlsE binding by patient serum antibodies. IR6 epitopes (by the C6 peptide) were found to dominate the response to invariable segments. IR6 (C6)-specific antibodies were detected in 78% of the serum specimens, whereas <40% of patients generated antibodies that bound the N- or C-terminal domain and <12% of patients responded to either IR2 or IR4. Interestingly, 15 of 37 patients generated IgG antibodies that reacted with C6 but not with VlsE. Conversely, IgM responses were frequent for VlsE but not for invariable segments. A representative number of the serum specimens (n= 8) that contained IgG antibodies reacting with both C6 and VlsE was assessed in competition experiments, using C6 as a competitor. Only half of these specimens contained IgG antibodies whose binding to VlsE could be inhibited >50% by competition with the added C6 peptide. The median percent inhibition was 45.5%. These findings indicate that IR6 epitopes are largely concealed from the VlsE molecular surface and that full-length VlsE-based diagnosis likely detects antibodies to conformational and/or variable region epitopes.


2021 ◽  
Author(s):  
Kathryn O’Connell ◽  
Nisha Nair ◽  
Kamalika Samanta ◽  
Jose F. Azevedo ◽  
Grant D. Brown ◽  
...  

AbstractLyme Disease presents unique challenges for public health efforts. We hypothesized that transfer of protective antibodies between mothers and offspring should occur after oral vaccination of C3H-HeN mice with E. coli overexpressing OspA. We present new evidence for maternal transfer of vaccine induced neutralizing anti-OspA IgG antibodies to mouse pups through ingestion of colostrum. Protective levels of OspA antibodies in pups were present from 2-5 weeks after birth and they persisted in some mice until 9 weeks of age. This was corroborated by detection of neutralizing antibodies in the serum of all pups at 2-3 weeks after birth and in some mice at 9 weeks of age. A clear association was found between robust antibody responses in mothers and the length of antibody persistence in the respective pups using a novel longitudinal Bayesian model. These factors are likely to impact the enzootic cycle of B. burgdorferi when reservoir targeted OspA-based vaccination interventions are implemented.


2021 ◽  
Author(s):  
Kevin John Selva ◽  
Samantha K Davis ◽  
Ebene R Haycroft ◽  
Wen Shi Lee ◽  
Ester Lopez ◽  
...  

Objectives SARS-CoV-2 can be transmitted by aerosols and the ocular surface may be an important route of transmission. Little is known about protective antibody responses to SARS-CoV-2 in tears after infection or vaccination. We analysed SARS-CoV-2 specific IgG and IgA responses in human tears after either COVID-19 infection or vaccination. Methods We recruited 16 subjects with COVID-19 infection an average of 7 months previously and 15 subjects before and 2 weeks after Comirnaty (Pfizer-BioNtech) vaccination. Plasma, saliva and basal tears were collected. Pre-pandemic plasma, saliva and basal tears from 11 individuals were included as healthy controls. Antibody responses to 5 SARS-CoV-2 antigens were measured via multiplex. Results IgG antibodies to Spike and Nucleoprotein were detected in tears, saliva and plasma from subjects with prior SARS-CoV-2 infection in comparison to uninfected controls. While RBD-specific antibodies were detected in plasma, minimal RBD-specific antibodies were detected in tears and saliva. In contrast, high levels of IgG antibodies to Spike and RBD, but not Nucleoprotein, were induced in tears, saliva and plasma of subjects receiving 2 doses of the Comirnaty vaccine. Increased levels of IgA1 and IgA2 antibodies to SARS-CoV-2 antigens were detected in plasma following infection or vaccination, but were unchanged in tears and saliva. Conclusion Both infection and vaccination induce SARS-CoV-2-specific IgG antibodies in tears. RBD-specific IgG antibodies in tears were induced by vaccination but were not present 7 months post-infection. This suggests neutralising antibodies may be low in the tears late following infection.


2020 ◽  
Author(s):  
Zezhong Liu ◽  
Wei Xu ◽  
Shuai Xia ◽  
Chenjian Gu ◽  
Xinling Wang ◽  
...  

Abstract The pandemic of COVID-19 caused by SARS-CoV-2 has posed serious threats to global health and economy, thus calling for the development of safe and effective vaccines. The receptor-binding domain (RBD) in the spike protein of SARS-CoV-2 is responsible for its binding to ACE2 receptor. It contains multiple dominant neutralizing epitopes and serves as an important antigen for the development of COVID-19 vaccines. Here, we showed that immunization of mice with a candidate subunit vaccine consisting of SARS-CoV-2 RBD and Fc fragment of human IgG, as an immunopotentiator, elicited high titer of RBD-specific antibodies with robust neutralizing activity against both pseudotyped and live SARS-CoV-2 infections. The mouse antisera could also effectively neutralize infection by pseudotyped SARS-CoV-2 with several natural mutations in RBD and the IgG extracted from the mouse antisera could also show neutralization against pseudotyped SARS-CoV and SARS-related coronavirus (SARSr-CoV). Vaccination of human ACE2 transgenic mice with RBD-Fc could effectively protect mice from the SARS-CoV-2 challenge. These results suggest that SARS-CoV-2 RBD-Fc has good potential to be further developed as an effective and broad-spectrum vaccine to prevent infection of the current SARS-CoV-2 and its mutants, as well as future emerging SARSr-CoVs and re-emerging SARS-CoV.


Author(s):  
Joanna Balcerek ◽  
Evelin Trejo ◽  
Kendall Levine ◽  
Paul Couey ◽  
Zoe V Kornberg ◽  
...  

Abstract Objectives Serologic testing for antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in potential donors of coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) may not be performed until after blood donation. A hospital-based recruitment program for CCP may be an efficient way to identify potential donors prospectively Methods Patients who recovered from known or suspected COVID-19 were identified and recruited through medical record searches and public appeals in March and April 2020. Participants were screened with a modified donor history questionnaire and, if eligible, were asked for consent and tested for SARS-CoV-2 antibodies (IgG and IgM). Participants positive for SARS-CoV-2 IgG were referred for CCP collection. Results Of 179 patients screened, 128 completed serologic testing and 89 were referred for CCP donation. IgG antibodies to SARS-CoV-2 were detected in 23 of 51 participants with suspected COVID-19 and 66 of 77 participants with self-reported COVID-19 confirmed by polymerase chain reaction (PCR). The anti–SARS-CoV-2 IgG level met the US Food and Drug Administration criteria for “high-titer” CCP in 39% of participants confirmed by PCR, as measured by the Ortho VITROS IgG assay. A wide range of SARS-CoV-2 IgG levels were observed. Conclusions A hospital-based CCP donor recruitment program can prospectively identify potential CCP donors. Variability in SARS-CoV-2 IgG levels has implications for the selection of CCP units for transfusion.


1994 ◽  
Vol 112 (2) ◽  
pp. 359-365 ◽  
Author(s):  
I. Nachamkin ◽  
S. H. Fischer ◽  
X.-H. Yang ◽  
O. Benitez ◽  
A. Cravioto

SUMMAYWe studied the relationship between IgA anti–campylobacter flagellin antibodies in breast milk samples and protection of breastfed infants living in a rural Mexican village from campylobacter infection. There were fewer episodes of campylobacter infection (symptomatic and asymptomatic combined) in infants breastfed with milk containing specific anti-flagellin antibodies (1.2/child/year, 95% CI 0.6–1.8) versus non–breastfed children (3.3/child/year, 95% CI 1.8–4.8; P < 0.01). Infants breastfed with milk that was antiflagellin antibody negative by ELISA also had fewer episodes of infection compared with non-breastfed children, but the difference did not reach statistical significance (1.8/child/year, 95% CI 0.7–3.0 versus 3.3/child/year, 95% CI 1.8–4.8, P > 0.05). Breastfeeding has a protective effect against campylobacter infection and is associated with the presence of specific antibodies directed against campylobacter flagellin.


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.


Author(s):  
Davide F. Robbiani ◽  
Christian Gaebler ◽  
Frauke Muecksch ◽  
Julio C. C. Lorenzi ◽  
Zijun Wang ◽  
...  

AbstractDuring the COVID-19 pandemic, SARS-CoV-2 infected millions of people and claimed hundreds of thousands of lives. Virus entry into cells depends on the receptor binding domain (RBD) of the SARS-CoV-2 spike protein (S). Although there is no vaccine, it is likely that antibodies will be essential for protection. However, little is known about the human antibody response to SARS-CoV-21–5. Here we report on 149 COVID-19 convalescent individuals. Plasmas collected an average of 39 days after the onset of symptoms had variable half-maximal neutralizing titers ranging from undetectable in 33% to below 1:1000 in 79%, while only 1% showed titers >1:5000. Antibody cloning revealed expanded clones of RBD-specific memory B cells expressing closely related antibodies in different individuals. Despite low plasma titers, antibodies to three distinct epitopes on RBD neutralized at half-maximal inhibitory concentrations (IC50s) as low as single digit ng/mL. Thus, most convalescent plasmas obtained from individuals who recover from COVID-19 do not contain high levels of neutralizing activity. Nevertheless, rare but recurring RBD-specific antibodies with potent antiviral activity were found in all individuals tested, suggesting that a vaccine designed to elicit such antibodies could be broadly effective.


2020 ◽  
Author(s):  
Pradeep Darshana Pushpakumara ◽  
Chandima Jeewandara ◽  
Laksiri Gomes ◽  
Yashodha Perera ◽  
Ananda Wijewickrama ◽  
...  

AbstractBackgroundAlthough immune responses to the Japanese Encephalitis virus (JEV), and the dengue viruses (DENV) have a potential to modulate the immune responses to each other, this has been poorly investigated. Therefore, we developed an ELISA to identify JEV specific, DENV non cross-reactive antibody responses by identifying JEV specific, highly conserved regions of the virus and proceeded to investigate if the presence of JEV specific antibodies associate with dengue disease severity.Methodology/Principal findings20 JEV specific peptides were identified from highly conserved regions of the virus and the immunogenicity and specificity of these peptides were assessed in individuals who were non-immune to JEV and DENV (JEV-DENV-, N=30), those who were only immune to the JEV and not DENV (JEV+DENV-, N=30), those who were only immune to DENV(JEV-DENV+, N=30) and in those who were immune to both viruses (JEV+DENV+, N=30). 7/20 peptides were found to be highly immunogenic and specific and these 7 peptides were used as a pool to further evaluate JEV-specific responses. All 30/30 JEV+DENV-and 30/30 JEV+DENV+individuals, and only 3/30 (10%) JEV-DENV+individuals responded to this pool. We further evaluated this pool of 7 peptides in patients following primary and secondary dengue infection during the convalescent period and found that the JEV-specific peptides, were unlikely to cross react with DENV IgG antibodies. We further compared this in-house ELISA developed with the peptide pool with an existing commercial JEV IgG assay to identify JEV-specific IgG following vaccination, and our in-house ELISA was found to be more sensitive. We then proceeded to investigate if the presence of JEV-specific antibodies were associated with dengue disease severity, and we found that those who had past severe dengue (n=175) were significantly more likely (p<0.0001) to have JEV-specific antibodies than those with past non-severe dengue (n=175) (OR 5.3, 95% CI 3.3 to 8.3).Conclusions/SignificanceAs our data show that this assay is highly sensitive and specific for detection of JEV-specific antibody responses, it would be an important tool to determine how JEV seropositivity modulate dengue immunity and disease severity when undertaking dengue vaccine trials.Author summaryBoth Japanese Encephalitis virus (JEV), and the dengue viruses (DENV) co-circulate in the same geographical region and have a potential to modulate the immune responses to each other. However, due to the difficulty in identifying antibody responses specific to either virus due to the highly cross-reactive nature of virus-specific antibodies, this has been poorly investigated. Therefore, we developed an ELISA to identify JEV-specific, DENV non cross-reactive antibody responses by identifying JEV-specific, highly conserved regions of the virus and proceeded to investigate if the presence of JEV-specific antibodies associates with dengue disease severity. 20 JEV-specific peptides were identified from highly conserved regions of the virus and the immunogenicity and specificity of these peptides were assessed. We found that seven peptides were highly immunogenic and specific to the JEV and we further evaluated the usefulness of an ELISA developed using these pools of peptides. We found that our in-house ELISA was found to be significantly more sensitive some of the existing commercial assays. As this assay appears to be highly sensitive and specific for detection of JEV-specific antibody responses, it would be an important tool to determine how JEV seropositivity modulate dengue immunity and disease severity when undertaking dengue vaccine trials.


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