Serum Antibody Responses of High-Risk Children and Adults to Vaccination with Capsular Polysaccharides of Streptococcus pneumoniae

1981 ◽  
Vol 3 (Supplement_1) ◽  
pp. S168-S178 ◽  
Author(s):  
G. Scott Giebink ◽  
Chap T. Le ◽  
Fernando G. Cosio ◽  
John S. Spika ◽  
Gerald Schiffman
Keyword(s):  
Streptococcus Pneumoniae ◽  
High Risk ◽  
Serum Antibody ◽  
Antibody Responses ◽  
Capsular Polysaccharides ◽  
High Risk Children

scholarly journals Serum Antibody Responses against Carbapenem-Resistant Klebsiella pneumoniae in Infected Patients

mSphere ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Kasturi Banerjee ◽  
Michael P. Motley ◽  
Elizabeth Diago-Navarro ◽  
Bettina C. Fries
Keyword(s):  
Klebsiella Pneumoniae ◽  
Capsular Polysaccharide ◽  
Serum Antibody ◽  
Antibody Responses ◽  
Capsular Polysaccharides ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Reactive Properties

ABSTRACT Capsular polysaccharide (CPS) heterogeneity within carbapenem-resistant Klebsiella pneumoniae (CR-Kp) strain sequence type 258 (ST258) must be considered when developing CPS-based vaccines. Here, we sought to characterize CPS-specific antibody responses elicited by CR-Kp-infected patients. Plasma and bacterial isolates were collected from 33 hospital patients with positive CR-Kp cultures. Isolate capsules were typed by wzi sequencing. Reactivity and measures of efficacy of patient antibodies were studied against 3 prevalent CR-Kp CPS types (wzi29, wzi154, and wzi50). High IgG titers against wzi154 and wzi50 CPS were documented in 79% of infected patients. Patient-derived (PD) IgGs agglutinated CR-Kp and limited growth better than naive IgG and promoted phagocytosis of strains across the serotype isolated from their donors. Additionally, poly-IgG from wzi50 and wzi154 patients promoted phagocytosis of nonconcordant CR-Kp serotypes. Such effects were lost when poly-IgG was depleted of CPS-specific IgG. Additionally, mice infected with wzi50, wzi154, and wzi29 CR-Kp strains preopsonized with wzi50 patient-derived IgG exhibited lower lung CFU than controls. Depletion of wzi50 antibodies (Abs) reversed this effect in wzi50 and wzi154 infections, whereas wzi154 Ab depletion reduced poly-IgG efficacy against wzi29 CR-Kp. We are the first to report cross-reactive properties of CPS-specific Abs from CR-Kp patients through both in vitro and in vivo models. IMPORTANCE Carbapenem-resistant Klebsiella pneumoniae is a rapidly emerging public health threat that can cause fatal infections in up to 50% of affected patients. Due to its resistance to nearly all antimicrobials, development of alternate therapies like antibodies and vaccines is urgently needed. Capsular polysaccharides constitute important targets, as they are crucial for Klebsiella pneumoniae pathogenesis. Capsular polysaccharides are very diverse and, therefore, studying the host’s capsule-type specific antibodies is crucial to develop effective anti-CPS immunotherapies. In this study, we are the first to characterize humoral responses in infected patients against carbapenem-resistant Klebsiella pneumoniae expressing different wzi capsule types. This study is the first to report the efficacy of cross-reactive properties of CPS-specific Abs in both in vitro and in vivo models.

Enhanced Immunological Responses Following K562/GM-CSF/CD40L Vaccine Plus Lenalidomide in High-Risk Myelodysplastic Syndrome

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1725-1725
Author(s):  
John Powers ◽  
Eric Padron ◽  
Jason Dubovsky ◽  
Emmanuel Berchmans ◽  
Tyler Farnum ◽  
...  
Keyword(s):  
High Risk ◽  
Immune Responses ◽  
Clinical Response ◽  
Conflicts Of Interest ◽  
Serum Antibody ◽  
Humoral Response ◽  
Antibody Responses ◽  
Gm Csf ◽  
Mrna Transcripts ◽  
Post Therapy

Abstract Abstract 1725 Introduction: Immunotherapeutic strategies have been limited by the lack of known tumor restricted antigens and inadequate immune responses. In our Institution, an ongoing Phase I dose escalation study in 11 high risk MDS patients, who failed hypo-methylating agents, were enrolled in a K562-GMCSF-CD40 ligand transfected “bystander” vaccine, in combination with lenalidomide, and have shown promising responses. Wilm's Tumor protein 1 (WT1) and Cancer Testis Antigens (CTAs) are solid candidates for future immunotherapy and vaccines containing these antigens are currently under development in solid and hematological malignancies. The K562 cell-line expresses both WT1 and numerous CTAs, the resultant immunization with this cellular vaccine is attractive for both immunological response and assessment. Here we describe immunological correlative studies before and after vaccination. Methods: We monitored the humoral response, of the four responders, to CTAs by SEREX High Throughput Immunoblot assay (HTI), 29 CTAs were bound in a concise pattern to nitrocellulose filters and developed in the following methodology. Patient sera were incubated with the HTI filters and any CTA specific antibodies bound to respective antigens and reactive antibodies were detected by secondary anti-human antibodies in a colorimetric assay. Filters were read by 6 blinded individuals, spots were scored positive or negative against control antigens. These results were compared to the paired post-therapy sample a score of 6 was maximal change of pre to post. Those CTAs with strong antibody presence post-therapy were then confirmed via ELISA resulting in an antibody titer reflected as ug/mL. A standardization of human IgG, as well as a healthy donor control was used to determine the validity of identified responses. An assessment of cellular immune responses was performed via interferon gamma (IFNγ) ELISPOT and a flow based peptide and lysate specific proliferation assay, using CD8+, CD137+ and CSFE, towards WT1 peptides and K562 lysates. Results: Of the 15 patients enrolled 4 had relevant clinical responses by IWG, 2 complete responses (CR), 1 marrow CR and 1 partial response. Upon initial examination of HTI filters, 4 patients who showed clinical response were observed to have increased serum antibody responses to multiple CTAs (10 of 29) at end of therapy or last evaluable date. Response to NY-SAR-35, MAGE family, NY-ESO1 and SSX2 had the strongest post-therapy signal confirmed via ELISA. RT-PCR of bone marrow aspirates revealed a range of 5 to 9 CTA mRNA transcripts present in responsive patients at baseline which subsequently decreased to a range of 1 to 5 at post-therapy. Increased (IFNγ) production was observed via elispot in an initial screening of a patient with clinical response at post-vaccination. IFNγ responsive cell number was increased independent to macrophage loaded with K562 lysate or WT1 peptides in this patient. This patient also exhibited a CD8+CD137+ proliferative response upon incubation with WT1 peptides and K562 lysate. Conclusion: An increased humoral response against CTAs was seen in patients with high risk MDS after treatment with a combination of lenalidomide and K562-GM-CSF-CD40L vaccine. A majority of these CTAs were expressed by the vaccine and the patients before treatment. Interestingly, some antigens, MAGE-A4 and SSX1 as examples, exhibited low antibody responses at baseline and elevated levels at post therapy but, mRNA transcripts were conversely correlated suggesting a possible immune response. Preliminary analysis demonstrated increased specific cellular responses to WT1 peptides or K562 lysates. Further analysis of the remaining responding patients will be presented. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Acquired, but Not Innate, Immune Responses to Streptococcus pneumoniae Are Compromised by Neutralization of CD40L

2000 ◽  
Vol 68 (2) ◽  
pp. 511-517 ◽  
Author(s):  
Young-il Hwang ◽  
Moon H. Nahm ◽  
David E. Briles ◽  
David Thomas ◽  
Jeffrey M. Purkerson
Keyword(s):  
Streptococcus Pneumoniae ◽  
Capsular Polysaccharide ◽  
Pneumococcal Infection ◽  
Systemic Infection ◽  
Humoral Response ◽  
Nasal Carriage ◽  
The Elderly ◽  
Antibody Responses ◽  
Capsular Polysaccharides ◽  
Cell Wall Polysaccharides

ABSTRACT Streptococcus pneumoniae is a significant pathogen of young children and the elderly. Systemic infection by pneumococci is a complex process involving several bacterial and host factors. We have investigated the role of CD40L in host defense against pneumococcal infection. Treatment of mice with MR-1 antibody (anti-CD154/CD40L) markedly reduced antibody responses to the pneumococcal protein PspA, elicited by immunization of purified protein or whole bacteria. In mice immunized with whole bacteria, MR-1 treatment reduced antibody responses to capsular polysaccharides but not cell wall polysaccharides. MR-1 did not suppress antibody responses to isolated capsular polysaccharides but did reduce the production of antibody to a capsular polysaccharide-protein conjugate, indicating that when presented in the context of whole bacteria, the humoral response to capsular polysaccharides is partially T-cell dependent. Despite the reduction of the protective humoral responses to pneumococcal infection, administration of MR-1 had no effect on sepsis, lung infection, or nasal carriage in nonimmune mice inoculated with virulent pneumococci. Thus, short-term neutralization of CD40L does not compromise innate host defenses against pneumococcal invasion.

scholarly journals Serotypes and Vaccine Coverage of Streptococcus Pneumoniae Colonization in the Nasopharynx of Thai Children in Congested Areas in Chiang Mai

Pathogens ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 988
Author(s):  
Anchalee Wangirapan ◽  
Satja Issaranggoon na Ayuthaya ◽  
Wasan Katip ◽  
Nongyao Kasatpibal ◽  
Raktham Mektrirat ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
High Risk ◽  
Invasive Pneumococcal Disease ◽  
Pneumococcal Disease ◽  
Vaccine Coverage ◽  
Chiang Mai ◽  
Nasopharyngeal Colonization ◽  
Conjugate Vaccines ◽  
High Risk Children ◽  
Congested Areas

Streptococcus pneumoniae causes around 10% of all deaths in children younger than five years of age. This study aimed to examine the serogroups/serotypes of S. pneumoniae colonization and vaccine serotype coverage of this organism among Thai children. Nasopharyngeal swabs of children less than or equal to 15 years of age were obtained in congested areas in Chiang Mai from 1 February 2013 to 1 August 2013. The serotyping of S. pneumoniae isolates was performed using the ImmuLex™ kit and the vaccine serotype coverage for this organism was evaluated. A total of 292 children were enrolled. One hundred and thirty children (44.5%) had nasopharyngeal colonization with Streptococcus pneumoniae. Eighty-seven (66.9%) isolates were from children younger than five years of age, seventeen (13.1%) were from children aged 6–10 years, and twenty-six (20%) were from children aged 11–15 years. The five most common serogroups/serotypes isolated were 6 (6A, 6B, 6C) (46.1%), 23 (23F, 23A, 23B) (14.6%), 19 (19F, 19A, 19B, 19C) (8.5%), 15 (15F, 15A, 15B, 15C) (6.9%), and 14 (6.1%). Vaccine serotype coverages in pneumococcal conjugate vaccines (PCV):PCV7, PCV10, and PCV13 were 79.1%, 83.6%, and 85.9%, respectively. There were significant increases in coverage between PCV7 and PCV10 (from 79.1% to 83.6%, p < 0.001), PCV7 and PCV13 (from 79.1% to 85.9%, p < 0.001), and PCV10 and PCV13 (from 83.6% to 85.9%, p < 0.001). The majority of pneumococcal serogroup/serotype colonization in the nasopharynx of Thai children in the studied areas was included in the current licensed pneumococcal conjugated vaccines (PCVs). PCV vaccination should be considered for high-risk children to reduce the incidence of invasive pneumococcal disease among Thai children.

Single Hepatitis B Booster Dose in High-risk Children with Suboptimal Surface Antigen Antibody Responses After 3-dose Primary Vaccine Series

2020 ◽  
Vol 57 (1) ◽  
pp. 68-69
Author(s):  
Jia-Ming Low ◽  
Le-Ye Lee ◽  
Michelle Li-Nien Tan ◽  
Michelle Hong ◽  
Si-Min Chan
Keyword(s):  
High Risk ◽  
Hepatitis B ◽  
Surface Antigen ◽  
Booster Dose ◽  
Antibody Responses ◽  
Antigen Antibody ◽  
High Risk Children

scholarly journals Clostridium difficile Vaccine and Serum Immunoglobulin G Antibody Response to Toxin A

2003 ◽  
Vol 71 (3) ◽  
pp. 1608-1610 ◽  
Author(s):  
Samer Aboudola ◽  
Karen L. Kotloff ◽  
Lorraine Kyne ◽  
Michel Warny ◽  
Eoin C. Kelly ◽  
...  
Keyword(s):  
High Risk ◽  
Clostridium Difficile ◽  
Immunoglobulin G ◽  
Strong Association ◽  
Serum Antibody ◽  
Test Group ◽  
Antibody Responses ◽  
Toxin A ◽  
High Level ◽  
Very High

ABSTRACT There is a strong association between serum antibody responses to toxin A and protection against Clostridium difficile diarrhea. A parenteral C. difficile toxoid vaccine induced very-high-level responses to anti-toxin A immunoglobulin G (IgG) in the sera of healthy volunteers. After vaccination, the concentrations of anti-toxin A IgG in the sera of all 30 recipients exceeded the concentrations that were associated with protection in previous clinical studies. Furthermore, the median concentration of serum anti-toxin A IgG in the test group was 50-fold higher than the previous threshold. These findings support the feasibility of using a vaccine to protect high-risk individuals against C. difficile-associated diarrhea and colitis.

Sign in / Sign up

Export Citation Format

Share Document