scholarly journals Prospective Longitudinal Analysis of Immune Responses in Pediatric Subjects After Pharyngeal Acquisition of Group A Streptococci

2017 ◽  
Vol 6 (2) ◽  
pp. 187-196 ◽  
Author(s):  
Nicholas D. Hysmith ◽  
Edward L. Kaplan ◽  
P. Patrick Cleary ◽  
Dwight R. Johnson ◽  
Thomas A. Penfound ◽  
...  
Keyword(s):  
Immune Responses ◽  
Group A Streptococcus ◽  
Natural Infection ◽  
Antibody Responses ◽  
Antigen Specificity ◽  
Throat Culture ◽  
Serum Samples ◽  
Missed Opportunities ◽  
Group A ◽  
Prospective Longitudinal

Abstract Background. Despite the significant burden of disease associated with infection by group A streptococcus (GAS), little is known about the human immune response to GAS antigens after natural infection. Methods. We evaluated 195 serum samples obtained prospectively over a consecutive 24-month period from 41 pediatric subjects who experienced a new pharyngeal GAS acquisition. An enzyme-linked immunoassay was used to determine the kinetics and antigen specificity of antibodies against 13 shared GAS antigens and 18 type-specific M peptides. The majority of the antigens tested are currently being considered as vaccine candidates. Results. Twelve M types of GAS were recovered from 41 subjects who experienced 51 new GAS acquisitions that elicited antibody responses against at least 1 of the 31 antigens tested (immunologically significant new GAS acquisitions). The immune responses to the 13 shared antigens were highly variable. Increases in antibody levels were detected against a mean of 3.5 shared antigens (range, 1–8). Antibody responses to the homologous M peptide were observed in 32 (63%) of the 51 episodes. Seven subjects acquired more than 1 M type of GAS. There were no new immunologically significant acquisitions of an M type against which the subject had preexisting antibodies to the homologous M peptide. Of the subjects with new GAS acquisition, 65% were asymptomatic, yet immune responses were detected against 1 or more GAS antigens. Immune responses to streptolysin O and/or deoxyribonuclease B were observed after 67% of the new GAS acquisitions. Persistently positive (>12 weeks) throat culture results were returned for 20% of the 41 subjects despite immune responses to homologous M peptides and/or shared antigens. Conclusions. The availability of throat culture results, GAS isolates, and serial serum samples collected prospectively over a 2-year period of observation provided a unique opportunity for us to assess the serologic status of pediatric subjects before and after new pharyngeal acquisitions of GAS. With the exception of antibody responses to the homologous M peptides, no clear pattern of immune responses against the remaining GAS antigens was seen. There were no new immunologically significant acquisitions ofemm types of GAS against which the subjects had preexisting elevated levels of antibodies against the homologous M peptide. The observation that 65% of new GAS acquisitions caused no symptoms yet were immunologically significant suggests that the majority of infections are not detected, which would result in missed opportunities for primary prevention of rheumatic fever and rheumatic heart disease with appropriate antimicrobial therapy.

scholarly journals Vaccination strategy and anti - SARS-CoV-2 S titers in healthcare workers of the INT – IRCCS “Fondazione Pascale” Cancer Center (Naples, Italy)

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Ernesta Cavalcanti ◽  
Maria Antonietta Isgrò ◽  
Domenica Rea ◽  
Lucia Di Capua ◽  
Giusy Trillò ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Healthcare Workers ◽  
Geometric Mean ◽  
Vaccination Strategy ◽  
Antibody Responses ◽  
Cancer Center ◽  
Serum Samples ◽  
Humoral Immune ◽  
History Of

Abstract Background Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and the resulting disease, coronavirus disease 2019 (COVID-19), have spread to millions of people globally, requiring the development of billions of different vaccine doses. The SARS-CoV-2 spike mRNA vaccine (named BNT162b2/Pfizer), authorized by the FDA, has shown high efficacy in preventing SARS-CoV-2 infection after administration of two doses in individuals 16 years of age and older. In the present study, we retrospectively evaluated the differences in the SARS-CoV-2 humoral immune response after vaccine administration in the two different cohorts of workers at the INT - IRCCS “Fondazione Pascale” Cancer Center (Naples, Italy): previously infected to SARS-CoV-2 subjects and not infected to SARS-CoV-2 subjects. Methods We determined specific anti-RBD (receptor-binding domain) titers against trimeric spike glycoprotein (S) of SARS-CoV-2 by Roche Elecsys Anti-SARS-CoV-2 S immunoassay in serum samples of 35 healthcare workers with a previous documented history of SARS-CoV-2 infection and 158 healthcare workers without, after 1 and 2 doses of vaccine, respectively. Moreover, geometric mean titers and relative fold changes (FC) were calculated. Results Both previously infected and not infected to SARS-CoV-2 subjects developed significant immune responses to SARS-CoV-2 after the administration of 1 and 2 doses of vaccine, respectively. Anti-S antibody responses to the first dose of vaccine were significantly higher in previously SARS-CoV-2-infected subjects in comparison to titers of not infected subjects after the first as well as the second dose of vaccine. Fold changes for subjects previously infected to SARS-CoV-2 was very modest, given the high basal antibody titer, as well as the upper limit of 2500.0 BAU/mL imposed by the Roche methods. Conversely, for naïve subjects, mean fold change following the first dose was low ($$ \overline{x} $$ x ¯ =1.6), reaching 3.8 FC in 72 subjects (45.6%) following the second dose. Conclusions The results showed that, as early as the first dose, SARS-CoV-2-infected individuals developed a remarkable and statistically significant immune response in comparison to those who did not contract the virus previously, suggesting the possibility of administering only one dose in previously SARS-CoV-2-infected subjects. FC for previously infected subjects should not be taken into account for the generally high pre-vaccination values. Conversely, FC for not infected subjects, after the second dose, were = 3.8 in > 45.0% of vaccinees, and ≤ 3.1 in 19.0%, the latter showing a potential susceptibility to further SARS-CoV-2 infection.

scholarly journals Positive Rate of Tests for Group a Streptococcus and Viral Features in Children with Acute Pharyngitis

Children ◽  
2021 ◽  
Vol 8 (7) ◽  
pp. 599
Author(s):  
Dasom Wi ◽  
Soo-Han Choi
Keyword(s):  
Laboratory Testing ◽  
Older Patients ◽  
Group A Streptococcus ◽  
Throat Culture ◽  
Acute Pharyngitis ◽  
Rapid Antigen Detection Test ◽  
Positive Rate ◽  
Group A ◽  
Centor Score ◽  
Low Prevalence

Group A streptococcus (GAS) is an important cause of acute pharyngitis. We investigated the positive rate of GAS tests and clinical viral features in children with acute pharyngitis. A retrospective review was conducted for patients <15 years old with both rapid antigen detection test (RADT) and throat culture results. Patients were excluded if they were diagnosed with influenza or had received antibiotics within two weeks before these tests. A total of 377 patients were eligible. The median age of patients was 3.5 years, and 45.4% of total patients were <3 years old. Among all patients, 68.7% had at least one viral feature, and 39% had more than two. The overall positiv rate for GAS was 11.4%. The GAS positive rate was significantly lower in patients <3 years old than in older patients (1.8% vs. 19.4%, p < 0.0001). The overall sensitivity and specificity of RADT were 75.0% (95% CI: 57.8–87.9) and 97.9% (95% CI: 95.8–99.2), respectively. The GAS positive rate was not significantly different between patients with and without viral features (12.4% vs. 9.3%, p = 0.4854). In patients aged 3–14 years, the GAS positive rate was not associated with the modified Centor score or the frequency of clinical viral features. Despite a low prevalence of GAS pharyngitis, testing for GAS was frequently performed in children <3 years old in this study. Appropriate use of laboratory testing for GAS pharyngitis and judicious prescription of antibiotics were imperative.

scholarly journals A Systems Biology Approach Identifies B Cell Maturation Antigen (BCMA) as a Biomarker Reflecting Oral Vaccine Induced IgA Antibody Responses in Humans

2021 ◽  
Vol 12 ◽  
Author(s):  
Lynda Mottram ◽  
Anna Lundgren ◽  
Ann-Mari Svennerholm ◽  
Susannah Leach
Keyword(s):  
Systems Biology ◽  
Immune Responses ◽  
B Cell ◽  
Vaccine Development ◽  
Oral Vaccine ◽  
Antibody Responses ◽  
Cell Maturation ◽  
Antigen Specificity ◽  
B Cell Maturation ◽  
B Cell Maturation Antigen

Vaccines against enteric diseases could improve global health. Despite this, only a few oral vaccines are currently available for human use. One way to facilitate such vaccine development could be to identify a practical and relatively low cost biomarker assay to assess oral vaccine induced primary and memory IgA immune responses in humans. Such an IgA biomarker assay could complement antigen-specific immune response measurements, enabling more oral vaccine candidates to be tested, whilst also reducing the work and costs associated with early oral vaccine development. With this in mind, we take a holistic systems biology approach to compare the transcriptional signatures of peripheral blood mononuclear cells isolated from volunteers, who following two oral priming doses with the oral cholera vaccine Dukoral®, had either strong or no vaccine specific IgA responses. Using this bioinformatical method, we identify TNFRSF17, a gene encoding the B cell maturation antigen (BCMA), as a candidate biomarker of oral vaccine induced IgA immune responses. We then assess the ability of BCMA to reflect oral vaccine induced primary and memory IgA responses using an ELISA BCMA assay on a larger number of samples collected in clinical trials with Dukoral® and the oral enterotoxigenic Escherichia coli vaccine candidate ETVAX. We find significant correlations between levels of BCMA and vaccine antigen-specific IgA in antibodies in lymphocyte secretion (ALS) specimens, as well as with proportions of circulating plasmablasts detected by flow cytometry. Importantly, our results suggest that levels of BCMA detected early after primary mucosal vaccination may be a biomarker for induction of long-lived vaccine specific memory B cell responses, which are otherwise difficult to measure in clinical vaccine trials. In addition, we find that ALS-BCMA responses in individuals vaccinated with ETVAX plus the adjuvant double mutant heat-labile toxin (dmLT) are significantly higher than in subjects given ETVAX only. We therefore propose that as ALS-BCMA responses may reflect the total vaccine induced IgA responses to oral vaccination, this BCMA ELISA assay could also be used to estimate the total adjuvant effect on vaccine induced-antibody responses, independently of antigen specificity, further supporting the usefulness of the assay.

scholarly journals Development of Polyelectrolyte Complexes for the Delivery of Peptide-Based Subunit Vaccines against Group A Streptococcus

Nanomaterials ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 823 ◽  
Author(s):  
Lili Zhao ◽  
Wanli Jin ◽  
Jazmina Gonzalez Cruz ◽  
Nirmal Marasini ◽  
Zeinab G. Khalil ◽  
...  
Keyword(s):  
Immune Responses ◽  
Subunit Vaccine ◽  
Group A Streptococcus ◽  
Vaccine Delivery ◽  
Surface Charges ◽  
Subunit Vaccines ◽  
Polyelectrolyte Complexes ◽  
Humoral Immune ◽  
Anionic Polymers ◽  
Group A

Peptide subunit vaccines hold great potential compared to traditional vaccines. However, peptides alone are poorly immunogenic. Therefore, it is of great importance that a vaccine delivery platform and/or adjuvant that enhances the immunogenicity of peptide antigens is developed. Here, we report the development of two different systems for the delivery of lipopeptide subunit vaccine (LCP-1) against group A streptococcus: polymer-coated liposomes and polyelectrolyte complexes (PECs). First, LCP-1-loaded and alginate/trimethyl chitosan (TMC)-coated liposomes (Lip-1) and LCP-1/alginate/TMC PECs (PEC-1) were examined for their ability to trigger required immune responses in outbred Swiss mice; PEC-1 induced stronger humoral immune responses than Lip-1. To further assess the adjuvanting effect of anionic polymers in PECs, a series of PECs (PEC-1 to PEC-5) were prepared by mixing LCP-1 with different anionic polymers, namely alginate, chondroitin sulfate, dextran, hyaluronic acid, and heparin, then coated with TMC. All produced PECs had similar particle sizes (around 200 nm) and surface charges (around + 30 mV). Notably, PEC-5, which contained heparin, induced higher antigen-specific systemic IgG and mucosal IgA titers than all other PECs. PEC systems, especially when containing heparin and TMC, could function as a promising platform for peptide-based subunit vaccine delivery for intranasal administration.

scholarly journals Study of Neuraminidase-Inhibiting Antibodies in Clinical Trials of Live Influenza Vaccines

Antibodies ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 20
Author(s):  
Yulia Desheva ◽  
Tatiana Smolonogina ◽  
Svetlana Donina ◽  
Larisa Rudenko
Keyword(s):  
Immune Response ◽  
Clinical Trials ◽  
Immune Responses ◽  
Influenza Infection ◽  
H1n1 Influenza ◽  
Antibody Responses ◽  
Influenza Vaccines ◽  
Statistical Relationship ◽  
Serum Samples ◽  
H5n1 Influenza

Background: Currently, the immunogenicity of influenza vaccines is assessed by detecting an increase of hemagglutination inhibition (HI) antibodies. As neuraminidase (NA)-based immunity may be significant in protecting against influenza infection, detection of neuraminidase inhibiting (NI) antibodies may improve the assessment of the immunogenicity of influenza vaccines. Methods: We investigated the immune response to NA in people after immunization with live influenza vaccines (LAIVs). A number of A/H7NX or A/H6NX viruses were used to detect NI antibodies, using an enzyme-linked lectin assay (ELLA). Results: Seasonal LAIV immunization stimulated an increase in NI antibodies not only to homologous A/H1N1 influenza, but also to A/H1N1pdm09 and A/H5N1 influenza. After A/17/California/09/38 (H1N1) pdm09 LAIV vaccination, there was no statistical relationship between post-vaccinated antibody seroconversion and two surface glycoproteins in serum samples obtained from the same individuals (p = 0.24). Vaccination with LAIV of H5N2, H2N2, H7N3, and H7N9 subtypes led to 7%–29.6% NI antibody seroconversions in the absence of HI antibody conversions. There was relatively low coordination of hemagglutinin (HA) and NA antibody responses (r = 0.24–0.59). Conclusions: The previously noted autonomy for HI and NI immune responses was confirmed when assessing the immunogenicity of LAIVs. Combining the traditional HI test with the detection of NI antibodies can provide a more complete assessment of LAIV immunogenicity.

FbaA- and M protein-based multi-epitope vaccine elicits strong protective immune responses against group A streptococcus in mouse model

2014 ◽  
Vol 16 (5) ◽  
pp. 409-418 ◽  
Author(s):  
Cuiqing Ma ◽  
Zheng Liu ◽  
Wenjian Li ◽  
Xuesong Qian ◽  
Song Zhang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Immune Responses ◽  
Group A Streptococcus ◽  
M Protein ◽  
Epitope Vaccine ◽  
Group A

scholarly journals Differential Immunogenicity of BNT162b2 or ChAdOx1 Vaccines After Extended-Interval Homologous Dual Vaccination in Older People

2021 ◽  
Author(s):  
Helen Parry ◽  
Rachel Bruton ◽  
Christine Stephens ◽  
Kevin Brown ◽  
Gayatri Amirthalingam ◽  
...  
Keyword(s):  
Immune Responses ◽  
Older People ◽  
Natural Infection ◽  
Cellular Responses ◽  
Antibody Responses ◽  
Vaccine Responses ◽  
Cell Responses ◽  
Boost Vaccine ◽  
The Uk ◽  
Cellular Immune

Abstract BackgroundSeveral SARS-CoV-2 vaccines have shown clinical efficacy against Covid-19 infection but there remains uncertainty about the immune responses elicited by different regimens. This is a particularly important question for older people who are at increased clinical risk following infection and in whom immune senescence may limit vaccine responses. The BNT162b2 mRNA and ChAdOx1 adenovirus vaccines were the first two vaccines deployed in the UK programme using an 8-12 week ‘extended interval’.ObjectivesWe undertook analysis of the spike-specific antibody and cellular immune response in 131 participants aged 80+ years after the second dose of ‘extended interval’ dual vaccination with either BNT162b2 mRNA (n=54) or ChAdOx1 (n=77) adenovirus vaccine. Blood samples were taken 2-3 weeks after second vaccine and were paired with samples taken at 5-weeks after first vaccine which have been reported previously. Antibody responses were measured using the Elecsys® electrochemiluminescence immunoassay assay and cellular responses were assessed by IFN-g ELISpot. ResultsAntibody responses against spike protein became detectable in all donors following dual vaccination with either vaccine. 4 donors had evidence of previous natural infection which is known to boost vaccine responses. Within the 53 infection-naïve donors the median antibody titre was 4030 U/ml (IQR 1892-8530) following BNT162b2 dual vaccination and 1405 (IQR 469.5- 2543) in the 74 patients after the ChAdOx1 vaccine (p=<0.0001). Spike-specific T cell responses were observed in 30% and 49% of mRNA and ChAdOx1 recipients respectively and median responses were 1.4-times higher in ChAdOx1 vaccinees at 14 vs 20 spots/million respectively (p=0.022).ConclusionDual vaccination with BNT162b2 or ChAdOx1 induces strong humoral immunity in older people following an extended interval protocol. Antibody responses are 2.9-times higher following the mRNA regimen whilst cellular responses are 1.7-times higher with the adenovirus-based vaccine. Differential patterns of immunogenicity are therefore elicited from the two vaccine platforms. It will be of interest to assess the relative stability of immune responses after these homologous vaccine regimens in order to assess the potential need for vaccine boosting. Furthermore, these findings indicate that heterologous vaccine platforms may offer the opportunity to further optimize vaccine responses.

scholarly journals Two doses of the SARS-CoV-2 BNT162b2 vaccine enhances antibody responses to variants in individuals with prior SARS-CoV-2 infection

2021 ◽  
pp. eabj0847
Author(s):  
Richard A Urbanowicz ◽  
Theocharis Tsoleridis ◽  
Hannah J Jackson ◽  
Lola Cusin ◽  
Joshua D Duncan ◽  
...  
Keyword(s):  
Immune Responses ◽  
Natural Infection ◽  
Neutralizing Antibody ◽  
Spike Protein ◽  
Serum Samples ◽  
Igg Antibody ◽  
Enzyme Immunoassays ◽  
Antigenic Exposure ◽  
The Impact ◽  
Prior Infection

Understanding the impact of prior infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the response to vaccination is a priority for responding to the coronavirus disease 2019 (COVID-19) pandemic. In particular, it is necessary to understand how prior infection plus vaccination can modulate immune responses against variants of concern. To address this, we sampled 20 individuals with and 25 individuals without confirmed previous SARS-CoV-2 infection from a large cohort of healthcare workers followed serologically since April 2020. All 45 individuals had received two doses of the Pfizer-BioNTech BTN162b2 vaccine with a delayed booster at 10 weeks. Absolute and neutralizing antibody titers against wild-type SARS-CoV-2 and variants were measured using enzyme immunoassays and pseudotype neutralization assays. We observed antibody reactivity against lineage A, B.1.351 and P.1 variants with increasing antigenic exposure, either through vaccination or natural infection. This improvement was further confirmed in neutralization assays using fixed dilutions of serum samples. The impact of antigenic exposure was more evident in enzyme immunoassays measuring SARS-CoV-2 spike protein-specific IgG antibody concentrations. Our data show that multiple exposures to SARS-CoV-2 spike protein in the context of a delayed booster expand the neutralizing breadth of the antibody response to neutralization-resistant SARS-CoV-2 variants. This suggests that additional vaccine boosts may be beneficial in improving immune responses against future SARS-CoV-2 variants of concern.

scholarly journals Evaluation of Rapid Antigen Detection Test for Group A Streptococci Pharyngitis among Children in an Out-Patient Clinic in Malaysia

2021 ◽  
Vol 50 (11) ◽  
pp. 3345-3354
Author(s):  
Zaili Zaki ◽  
Asrul Abdul Wahab ◽  
Ramliza Ramli ◽  
Afaaf Esa ◽  
Ezura Madiana Md. Monoto
Keyword(s):  
Sore Throat ◽  
Sensitivity And Specificity ◽  
Throat Swab ◽  
Group A Streptococcus ◽  
Antigen Detection ◽  
Preschool Age ◽  
Throat Culture ◽  
Care Clinic ◽  
Rapid Antigen Detection Test ◽  
Group A

One of the most common conditions encountered in the out-patient setting is acute pharyngitis. Group A Streptococcus (GAS) accounts for 15%-30% of cases of sore throat particularly in children under 15 years old. Rapid antigen testing (RADT) is an alternative diagnostic method to detect GAS pharyngitis. This study was done to evaluate the agreement between RADT whereby BIONEXIA® Strep A Plus (BioMérieux, France) kit was used and throat culture in the diagnosis of GAS pharyngitis in children presented with a sore throat. One hundred and ten children from a primary health care clinic with sore throat were included in this study. All children were evaluated based on McIsaac scoring and throat swab samples were taken for both throat culture and RADT testing. The prevalence of GAS pharyngitis by RADT in this study was 7.3% over one year. A higher incidence of GAS pharyngitis was noted in the school-aged children than the preschool-age children. There was no correlation between cough, lymph node enlargement, and tonsillar enlargement in predicting GAS pharyngitis. The sensitivity and specificity of RADT were 100% and 98%, respectively, when taking throat culture as a gold standard. A good agreement between RADT and throat culture was achieved (k=0.848). McIsaac scoring was noted to have good predictability for GAS pharyngitis with AUC=0.82. In conclusion, the rapid streptococcal antigen detection test showed excellent sensitivity and specificity and detecting GAS from the throat swab samples. Thus, it can be used to aid in the diagnosis of group A Streptococcal pharyngitis and could reduce the overuse of antibiotics. McIsaac score has also proven to be useful as a screening tool for bacterial pharyngitis.

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