scholarly journals Comprehensive antibody profiling of mRNA vaccination in children

2021 ◽  
Author(s):  
Yannic C Bartsch ◽  
Kerri J St Denis ◽  
Paulina Kaplonek ◽  
Jaewon Kang ◽  
Evan C Lam ◽  
...  
Keyword(s):  
Immune Response ◽  
Young Children ◽  
Receptor Binding ◽  
Humoral Immune Response ◽  
Antibody Responses ◽  
Fcγ Receptor ◽  
Humoral Immune ◽  
Antibody Titers ◽  
Antibody Profiling ◽  
Vaccines For Children

With the emergence of SARS-CoV-2 variants, fluctuating mask mandates, and school re-openings, increased infections and disease surged among children recently. Thus, there is an urgent need for COVID-19 vaccines for children of all ages. However, whether young children will respond appropriately to mRNA vaccines remains unclear. Here, we deeply profiled the vaccine-induced humoral immune response in 7-11 year old children receiving the mRNA-1273 vaccine. Vaccinated children induced significantly higher antibody titers and functions compared to naturally infected children. Moreover, we observed comparable SARS-CoV-2 titers and neutralizing activity across variants of concern and superior Fcγ-receptor binding and phagocytic antibodies in children compared to vaccinated adults. Our data indicate that mRNA vaccination elicits robust antibody responses and drives superior antibody functionality in children.

scholarly journals Bordetella pertussis Filamentous Hemagglutinin Enhances the Immunogenicity of Liposome-Delivered Antigen Administered Intranasally

1998 ◽  
Vol 66 (4) ◽  
pp. 1764-1767 ◽  
Author(s):  
Odile Poulain-Godefroy ◽  
Nathalie Mielcarek ◽  
Nathalie Ivanoff ◽  
Franck Remoué ◽  
Anne-Marie Schacht ◽  
...  
Keyword(s):  
Immune Response ◽  
Bordetella Pertussis ◽  
Humoral Immune Response ◽  
Dependent Manner ◽  
Humoral Immune ◽  
Filamentous Hemagglutinin ◽  
Antibody Titers ◽  
Suboptimal Dose ◽  
Outbred Mice ◽  
Dose Dependent

ABSTRACT In an attempt to increase the immunogenicity of mucosally delivered antigens, we incorporated the Bordetella pertussisfilamentous hemagglutinin (FHA) adhesin into liposomes containing the glutathione S-transferase of Schistosoma mansoni (Sm28GST) as a model antigen. Outbred mice immunized twice intranasally with liposomes containing a constant suboptimal dose of Sm28GST and increasing doses of FHA produced anti-Sm28GST antibodies in a FHA dose-dependent manner. The addition of 3 μg of FHA to the liposomes induced more than 10-fold-higher anti-Sm28GST antibody titers, compared to those induced by liposomes without FHA. The presence of FHA did not alter the nature of the humoral immune response, and the sera contained anti-Sm28GST immunoglobulin G1 (IgG1), IgG2a, and IgG2b. However, anti-Sm28GST IgA was only detected when at least 3 μg of FHA was added to the preparation. These results show a promising potential for FHA to enhance the immunogenicity of mucosally administered antigens incorporated into liposomes.

scholarly journals Recombinant Mycobacterium paragordonae Expressing SARS-CoV-2 Receptor-Binding Domain as a Vaccine Candidate Against SARS-CoV-2 Infections

2021 ◽  
Vol 12 ◽  
Author(s):  
Byoung-Jun Kim ◽  
Hyein Jeong ◽  
Hyejun Seo ◽  
Mi-Hyun Lee ◽  
Hyun Mu Shin ◽  
...  
Keyword(s):  
Immune Response ◽  
Single Dose ◽  
Immune Responses ◽  
Receptor Binding ◽  
Humoral Immune Response ◽  
Vaccine Candidate ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
Live Virus ◽  
Humoral Immune

At present, concerns that the recent global emergence of SARS-CoV-2 variants could compromise the current vaccines have been raised, highlighting the urgent demand for new vaccines capable of eliciting T cell-mediated immune responses, as well as B cell-mediated neutralizing antibody production. In this study, we developed a novel recombinant Mycobacterium paragordonae expressing the SARS-CoV-2 receptor-binding domain (RBD) (rMpg-RBD-7) that is capable of eliciting RBD-specific immune responses in vaccinated mice. The potential use of rMpg-RBD-7 as a vaccine for SARS-CoV-2 infections was evaluated in in vivo using mouse models of two different modules, one for single-dose vaccination and the other for two-dose vaccination. In a single-dose vaccination model, we found that rMpg-RBD-7 versus a heat-killed strain could exert an enhanced cell-mediated immune (CMI) response, as well as a humoral immune response capable of neutralizing the RBD and ACE2 interaction. In a two-dose vaccination model, rMpg-RBD-7 in a two-dose vaccination could also exert a stronger CMI and humoral immune response to neutralize SARS-CoV-2 infections in pseudoviral or live virus infection systems, compared to single dose vaccinations of rMpg-RBD or two-dose RBD protein immunization. In conclusion, our data showed that rMpg-RBD-7 can lead to an enhanced CMI response and humoral immune responses in mice vaccinated with both single- or two-dose vaccination, highlighting its feasibility as a novel vaccine candidate for SARS-CoV-2. To the best of our knowledge, this study is the first in which mycobacteria is used as a delivery system for a SARS-CoV-2 vaccine.

scholarly journals Suboptimal Humoral Immune Response against Influenza A(H7N9) Virus Is Related to Its Internal Genes

2015 ◽  
Vol 22 (12) ◽  
pp. 1235-1243 ◽  
Author(s):  
Andrew C. Y. Lee ◽  
Houshun Zhu ◽  
Anna J. X. Zhang ◽  
Can Li ◽  
Pui Wang ◽  
...  
Keyword(s):  
Immune Response ◽  
Virus Infection ◽  
Humoral Immune Response ◽  
Neutralizing Antibodies ◽  
Influenza A ◽  
Case Fatality ◽  
H7n9 Virus ◽  
Humoral Immune ◽  
Homologous Virus ◽  
Antibody Titers

ABSTRACTInfluenza A(H7N9) virus pneumonia is associated with a high case fatality rate in humans. Multiple viral factors have been postulated to account for the high virulence of the virus. It has been reported that patients with influenza A(H7N9) virus infection have relatively low titers of neutralizing antibodies compared to those with seasonal influenza virus infections. In this study, we compared serum hemagglutination inhibition (HI) and microneutralization (MN) antibody titers of mice challenged with wild-type A(H7N9) viruses [H7N9(Anhui) and H7N9(Zhejiang)], an A(H1N1)pdm09 virus [pH1N1(2009)], and a recombinant A(H7N9) virus with PR8/H1N1 internal genes (rg-PR8-H7-N9). All mice infected by H7N9(Anhui) and H7N9(Zhejiang) developed serum HI antibodies at 14 days postinfection (dpi) but no detectable MN antibodies, even at 28 dpi. A low level of neutralizing activity was detected in H7N9(Anhui)- and H7N9(Zhejiang)-infected mice using fluorescent focus MN assay, but convalescent-phase serum samples obtained from H7N9(Anhui)-infected mice did not reduce the mortality of naive mice after homologous virus challenge. Reinfection with homologous A(H7N9) virus induced higher HI and MN titers than first infection. In contrast, pH1N1(2009) virus infection induced robust HI and MN antibody responses, even during the first infection. Moreover, rg-PR8-H7-N9 induced significantly higher HI and MN antibody titers than H7N9(Zhejiang). In conclusion, the internal genes of A(H7N9) virus can affect the humoral immune response against homologous viral surface proteins, which may also contribute to the virulence of A(H7N9) virus.

scholarly journals Characterization of the Humoral Immune Response to Porcine Reproductive and Respiratory Syndrome (PRRS) Virus Infection

1995 ◽  
Vol 7 (3) ◽  
pp. 305-312 ◽  
Author(s):  
Kyoung-Jin Yoon ◽  
Jeffrey J. Zimmerman ◽  
Sabrina L. Swenson ◽  
Michael J. McGinley ◽  
Ken A. Eernisse ◽  
...  
Keyword(s):  
Immune Response ◽  
Humoral Immune Response ◽  
Fluorescent Antibody ◽  
Viral Proteins ◽  
Immunoblot Analysis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Prrs Virus ◽  
Humoral Immune ◽  
Antibody Titers ◽  
Rate Of Decline

The development of the humoral immune response against porcine reproductive and respiratory syndrome (PRRS) virus was monitored by an indirect fluorescent antibody (IFA) test, immunoperoxidase monolayer assay (IPMA), enzyme-linked immunosorbent assay (ELISA), and serum virus neutralization (SVN) test over a 105-day period in 8 pigs experimentally infected with ATCC strain VR-2402. Specific antibodies against PRRS virus were first detected by the IFA test, IPMA, ELISA, and the SVN test 9-11, 5-9, 9-13, and 9-28 days postinoculation (PI), respectively, and reached their maximum values by 4-5, 5-6, 4-6, and 10-11 weeks PI, respectively, thereafter. After reaching maximum value, all assays showed a decline in antibody levels. Assuming a constant rate of antibody decay, it was estimated by regression analysis that the ELISA, IFA, IPMA, and SVN antibody titers would approach the lower limits of detection by approximately days 137, 158, 324, and 356 PI, respectively. In this study, the immunoperoxidase monolayer assay appeared to offer slightly better performance relative to the IFA test, ELISA, and SVN test in terms of earlier detection and slower rate of decline in antibody titers. Western immunoblot analysis revealed that antibody specific for the 15-kD viral protein was present in all pigs by 7 days PI and persisted throughout the 105-day observation period. Initial detection of antibodies to the 19-, 23-, and 26-kD proteins varied among pigs, ranging from 9 to 35 days PI. Thereafter, the antibody responses to these 3 viral proteins of PRRS virus continued to be detected throughout the 105-day study period. These results clearly indicate that the 15-kD protein is the most immunogenic of the 4 viral proteins identified and may provide the antigenic basis for the development of improved diagnostic tests for the detection of PRRS virus antibodies.

scholarly journals Caprine humoral response to Burkholderia pseudomallei antigens during acute melioidosis from aerosol exposure

2018 ◽  
Author(s):  
Jinhee Yi ◽  
Mukoma F. Simpanya ◽  
Erik W. Settles ◽  
Austin B. Shannon ◽  
Karen Hernandez ◽  
...  
Keyword(s):  
Immune Response ◽  
Humoral Immune Response ◽  
Burkholderia Pseudomallei ◽  
Humoral Response ◽  
Antibody Responses ◽  
Protein Profiling ◽  
Common Source ◽  
Humoral Immune ◽  
Antigenic Proteins ◽  
Immunogenic Proteins

AbstractBurkholderia pseudomalleicauses melioidosis, a common source of pneumonia and sepsis in Southeast Asia and Northern Australia, that results in high mortality rates. A caprine melioidosis model of aerosol infection that leads to a systemic infection has the potential to characterize the humoral immune response. This could help identify immunogenic proteins for new diagnostics and vaccine candidates. Outbred goats may more accurately mimic human infection, in contrast to the inbred mouse models used to date.B. pseudomalleiinfection was delivered as an intratracheal aerosol. Antigenic protein profiling was generated from the infecting strain MSHR511. Humoral immune responses were analyzed by ELISA and western blot, and the antigenic proteins were identified by mass spectrometry. Throughout the course of the infection the assay results demonstrated a much greater humoral response with IgG antibodies, in both breadth and quantity, compared to IgM antibodies. Pre-infection sera showed multiple immunogenic proteins already reactive for IgG (7-20) and IgM (0-12) in most of the goats despite no previous exposure toB. pseudomallei. After infection, the number of IgG reactive proteins showed a marked increase as the disease progressed. Early stage infection (day 7) showed immune reaction to chaperone proteins (GroEL, EF-Tu, and DnaK). These three proteins were detected in all serum samples after infection, with GroEL immunogenically dominant. Seven common reactive antigens were selected for further analysis using ELISA. The heat shock protein GroEL1 elicited the strongest goat antibody immune response compared to the other six antigens. Most of the six antigens showed the peak IgM reactivity at day 14, whereas the IgG reactivity increased further as the disease progressed. An overall MSHR511 proteomic comparison between the goat model and human sera showed that many immune reactive proteins are common between humans and goats with melioidosis.Author SummaryB. pseudomalleiinfection, the causative agent of melioidosis, results in severe disseminated or localized infections. A systemic study of the humoral immune response toB. pseudomalleiinfection using theB. pseudomalleiaerosol caprine model would help understand the detectable antigenic proteins as the infection progresses. To study the immune response, IgG and IgM antibody responses to whole cell lysate proteins were identified and analyzed. Antigenic carbohydrates were also studied. From the results, this study suggests that the caprine humoral immune response to aerosolizedB. pseudomalleihas similarities to human melioidosis and may facilitate the analysis of the temporal antibody responses. In addition, commonly detected immunogenic proteins may be used as biomarkers for the future point of care (POC) diagnostics.

scholarly journals Characterization of the Humoral Immune Response Induced after Infection with Atypical Porcine Pestivirus (APPV)

Viruses ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 880 ◽  
Author(s):  
Gökce Nur Cagatay ◽  
Denise Meyer ◽  
Michael Wendt ◽  
Paul Becher ◽  
Alexander Postel
Keyword(s):  
Immune Response ◽  
Humoral Immune Response ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Humoral Immune ◽  
Neutralizing Capacity ◽  
Antibody Titers ◽  
Antibody Levels ◽  
Congenital Tremor

Atypical porcine pestivirus (APPV) is a widely distributed pathogen causing congenital tremor (CT) in piglets. So far, no data are available regarding the humoral immune response against APPV. In this study, piglets and their sows from an affected herd were tested longitudinally for viral genome and antibodies. APPV genome was detected in the majority of the piglets (14/15) from CT affected litters. Transient infection of gilts was observed. Kinetics of Erns- and E2-specific antibodies and their neutralizing capacity were determined by recently (Erns) and newly (E2) developed antibody ELISAs and virus neutralization assays. Putative maternally derived antibodies (MDA) were detected in most piglets, but displayed only low to moderate neutralizing capacity (ND50 ≤ 112). Horizontal APPV transmission occurred when uninfected and infected piglets were mingled on the flat deck. Horizontally infected piglets were clinically inapparent and showed only transient viremia with subsequently consistently high E2 antibody levels. For piglets from CT affected litters, significantly lower neutralizing antibody titers were observed. Results indicate that E2 represents the main target of neutralizing antibodies. Characterization of the humoral immune response against APPV will help to provide valuable serological diagnosis, to understand the epidemiology of this novel pathogen, and to implement tailored prevention strategies.

scholarly journals A compromised specific humoral immune response against the SARS-CoV-2 receptor-binding domain is related to viral persistence and periodic shedding in the gastrointestinal tract

2020 ◽  
Vol 17 (11) ◽  
pp. 1119-1125 ◽  
Author(s):  
Fengyu Hu ◽  
Fengjuan Chen ◽  
Zhihua Ou ◽  
Qinghong Fan ◽  
Xinghua Tan ◽  
...  
Keyword(s):  
Immune Response ◽  
Gastrointestinal Tract ◽  
Receptor Binding ◽  
Humoral Immune Response ◽  
Clinical Manifestations ◽  
Viral Persistence ◽  
Binding Domain ◽  
Health Concern ◽  
Receptor Binding Domain ◽  
Humoral Immune

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been redetected after discharge in some coronavirus disease 2019 (COVID-19) patients. The reason for the recurrent positivity of the test and the potential public health concern due to this occurrence are still unknown. Here, we analyzed the viral data and clinical manifestations of 289 domestic Chinese COVID-19 patients and found that 21 individuals (7.3%) were readmitted for hospitalization after detection of SARS-CoV-2 after discharge. First, we experimentally confirmed that the virus was involved in the initial infection and was not a secondary infection. In positive retests, the virus was usually found in anal samples (15 of 21, 71.4%). Through analysis of the intracellular viral subgenomic messenger RNA (sgmRNA), we verified that positive retest patients had active viral replication in their gastrointestinal tracts (3 of 16 patients, 18.7%) but not in their respiratory tracts. Then, we found that viral persistence was not associated with high viral titers, delayed viral clearance, old age, or more severe clinical symptoms during the first hospitalization. In contrast, viral rebound was associated with significantly lower levels of and slower generation of viral receptor-binding domain (RBD)-specific IgA and IgG antibodies. Our study demonstrated that the positive retest patients failed to create a robust protective humoral immune response, which might result in SARS-CoV-2 persistence in the gastrointestinal tract and possibly in active viral shedding. Further exploration of the mechanism underlying the rebound in SARS-CoV-2 in this population will be crucial for preventing virus spread and developing effective vaccines.

scholarly journals Serological assessment of SARS-CoV-2 infection during the first wave of the pandemic in Louisville Kentucky

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Krystal T. Hamorsky ◽  
Adrienne M. Bushau-Sprinkle ◽  
Kathleen Kitterman ◽  
Julia M. Corman ◽  
Jennifer DeMarco ◽  
...  
Keyword(s):  
Immune Response ◽  
Sensitivity And Specificity ◽  
Immunosorbent Assay ◽  
Receptor Binding ◽  
Healthcare Workers ◽  
Antibody Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Receptor Binding Domain ◽  
Iga Antibodies ◽  
Antibody Titers

AbstractSerological assays intended for diagnosis, sero-epidemiologic assessment, and measurement of protective antibody titers upon infection or vaccination are essential for managing the SARS-CoV-2 pandemic. Serological assays measuring the antibody responses against SARS-CoV-2 antigens are readily available. However, some lack appropriate characteristics to accurately measure SARS-CoV-2 antibodies titers and neutralization. We developed an Enzyme-linked Immunosorbent Assay (ELISA) methods for measuring IgG, IgA, and IgM responses to SARS-CoV-2, Spike (S), receptor binding domain (RBD), and nucleocapsid (N) proteins. Performance characteristics of sensitivity and specificity have been defined. ELISA results show positive correlation with microneutralization and Plaque Reduction Neutralization assays with infectious SARS-CoV-2. Our ELISA was used to screen healthcare workers in Louisville, KY during the first wave of the local pandemic in the months of May and July 2020. We found a seropositive rate of approximately 1.4% and 2.3%, respectively. Our analyses demonstrate a broad immune response among individuals and suggest some non-RBD specific S IgG and IgA antibodies neutralize SARS-CoV-2.

scholarly journals Antibiotics Modulate Vaccine-Induced Humoral Immune Response

1999 ◽  
Vol 6 (6) ◽  
pp. 832-837 ◽  
Author(s):  
Patrick C. Y. Woo ◽  
Hoi-Wah Tsoi ◽  
Lei-Po Wong ◽  
Harry C. H. Leung ◽  
Kwok-Yung Yuen
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Antibody Level ◽  
Tetanus Toxoid ◽  
Humoral Immune Response ◽  
Polysaccharide Vaccine ◽  
Antibody Responses ◽  
Pneumococcal Polysaccharide Vaccine ◽  
Humoral Immune ◽  
Antibody Levels

ABSTRACT The effects of antibiotics on the antigen-specific humoral immune response are not known. Macrolides, tetracyclines, and beta-lactams are commonly prescribed antibiotics. The first two are known to have immunomodulatory activities. The effects of clarithromycin, doxycycline, and ampicillin on the primary and secondary antibody responses to tetanus toxoid, a pneumococcal polysaccharide vaccine, a hepatitis B virus surface antigen (HBsAg) vaccine, and live attenuatedSalmonella typhi (Ty21a) were investigated using a mouse model. For the mice receiving the tetanus toxoid, the immunoglobulin M (IgM) level of the clarithromycin group at day 7 was significantly lower than the corresponding antibody level of the normal saline (NS) group. For the mice receiving the pneumococcal polysaccharide vaccine, the total antibody and IgM levels of the clarithromycin group and the IgM level of the doxycycline group at day 7 were significantly lower than the corresponding antibody levels of the ampicillin and NS groups. For the mice receiving the HBsAg vaccine, the IgM level of the doxycycline group at day 7 was significantly lower than the corresponding antibody levels of the clarithromycin and NS groups, while the IgM level of the clarithromycin group at day 28 was significantly lower than the corresponding antibody levels of the doxycycline, ampicillin, and NS groups. For the mice receiving all three vaccines, there were no statistically significant differences between any of the antibody levels of the ampicillin group and the corresponding antibody levels of the NS group. For the mice receiving Ty21a, the total antibody levels of the ampicillin group at days 7 and 21 were significantly higher than the corresponding antibody levels of the NS group. Moreover, the IgM levels of the clarithromycin, doxycycline, and ampicillin groups at days 7 and 21 were significantly higher than the corresponding antibody levels of the NS group. Furthermore, the total antibody level of the ampicillin group at day 21 was significantly higher than the corresponding antibody level of the doxycycline group. For all four vaccines, there were no statistically significant differences among the serum levels of interleukin-10 and gamma interferon for the mice treated with the various antibiotics. We conclude that clarithromycin and doxycycline, but not ampicillin, suppress the antibody responses of mice to T-cell-dependent and T-cell-independent antigens, whereas all three antibiotics enhance the antibody response to live attenuated mucosal bacterial vaccines.

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