Anti-Pneumococcal Vaccine-Induced Cellular Immune Responses in Post-Traumatic Splenectomized Individuals

Karasartova, Djursun; Gazi, Umut; Tosun, Özgür; Güreser, Ayşe Semra; Şahiner, İbrahim Tayfun; Dolapci, Mete; Özkan, Ayşegül Taylan

doi:10.1007/s10875-017-0397-3

Cited by 9 publications

(13 citation statements)

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“…Splenectomy has the potential to influence the memory cell generation as it was previously suggested to affect the level of cellular immune responses . This was investigated by comparing the levels of vaccine‐specific IFN‐γ‐secreting memory T cells.…”

Section: Resultsmentioning

confidence: 99%

“…This was investigated by comparing the levels of vaccine‐specific IFN‐γ‐secreting memory T cells. IFN‐γ was the cytokine of choice since the conjugated anti‐pneumococcal vaccination was previously shown to induce a T H 1 immune response …”

Section: Resultsmentioning

confidence: 99%

“…IFNγ was the cytokine of choice since the conjugated antipneumococcal vaccination was previously shown to induce a T H 1 immune response. 16,22 The ELISPOT analysis revealed that the numbers of PCV-13- 110.21 ± 10.41 and 103.00 ± 5.52 in asplenic individuals) (Figure 1).…”

Section: Splenectomy Influences the Generation Of Pcv-13 Specific Mmentioning

confidence: 99%

“…Splenectomy has the potential to influence the memory cell generation as it was previously suggested to affect the level of cellular immune responses. 14,15,22 This was investigated by comparing the levels of vaccine-specific IFNγ-secreting memory T cells. IFNγ was the cytokine of choice since the conjugated antipneumococcal vaccination was previously shown to induce a T H 1 immune response.…”

Section: Splenectomy Influences the Generation Of Pcv-13 Specific Mmentioning

confidence: 99%

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The effect of splenectomy on the levels of PCV-13-induced memory B- and T cells

et al. 2018

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Our results suggest that spleen is important, but not essential, for survival and/or generation of memory IgG B cells. In contrast, it seems to be indispensable for PCV-13-specific memory T 1-cell levels. Studies enhancing the levels of vaccine-induced memory cells and further enlightening the immune responses in asplenic individuals are required to develop more effective vaccination strategies against OPSI.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Splenectomy Influences the Generation Of Pcv-13 Specific Mmentioning

confidence: 99%

Section: Splenectomy Influences the Generation Of Pcv-13 Specific Mmentioning

confidence: 99%

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The effect of splenectomy on the levels of PCV-13-induced memory B- and T cells

et al. 2018

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“…Providing a more natural microenvironment with minimal manipulation likely contributed to the ability of our human in vitro system to mirror in vivo vaccine responses, including: (1) innate DC maturation and migration in response to adjuvants and the self-adjuvanted BCG vaccine ( 71 ); (2) BCG-induced increase of plasma ADA activity in infants, a reported in vivo biomarker of infant BCG immunization ( 72 ) that we independently confirmed; (3) limited T lymphocyte proliferation in response to the T cell-independent pneumococcal polysaccharide vaccine ( 73 ); (4) vaccine-induced patterns of antigen-recall T cell cytokines, chemokines, and lymphoproliferation ( 2 , 20 , 34 , 35 , 37 , 39 – 56 , 64 – 66 ) (Supplementary Table 4 ); and (5) single-antigen responses with dosing and plasma requirements matching those needed to generate protective immunity in vivo [i.e., a single dose for BCG ( 23 , 59 ) vs. multiple doses for HBV ( 64 )]. Moreover, comparison of newborn and adult responses demonstrated that multiple aspects of our results also match age-specific differences noted in other human in vitro and in vivo studies ( 2 , 24 , 31 , 32 , 74 ), suggesting the validity of our approach: (i) greater and broader adult DC maturation and lymphoproliferation to a range of adjuvants and vaccines ( 69 ), with the notable exception of robust neonatal DC maturation by TLR7/8A, recently shown to be a highly effective neonatal vaccine adjuvant in vivo ( 71 ); (ii) increased responsiveness of newborn leukocytes in the presence of adult plasma, and lower responsiveness of adult cells cultured in newborn plasma ( 24 ); (iii) lower newborn plasma ADA activity baseline ( 62 ); (iv) higher adult cognate T cell responsiveness paralleling study participant vaccination history and immune status ( 74 ); and a narrower and Th1-polarized cytokine profile by BCG-immunized adults ( 75 ) as compared to a broader Th1/Th2 mixed profile by newborns in vivo ( 20 , 34 , 35 , 39 – 55 ).…”

Section: Discussionmentioning

confidence: 99%

Microphysiologic Human Tissue Constructs Reproduce Autologous Age-Specific BCG and HBV Primary Immunization in vitro

et al. 2018

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Current vaccine development disregards human immune ontogeny, relying on animal models to select vaccine candidates targeting human infants, who are at greatest risk of infection worldwide, and receive the largest number of vaccines. To help accelerate and de-risk development of early-life effective immunization, we engineered a human age-specific microphysiologic vascular-interstitial interphase, suitable for pre-clinical modeling of distinct age-targeted immunity in vitro. Our Tissue Constructs (TCs) enable autonomous extravasation of monocytes that undergo rapid self-directed differentiation into migratory Dendritic Cells (DCs) in response to adjuvants and licensed vaccines such as Bacille Calmette-Guérin (BCG) or Hepatitis B virus Vaccine (HBV). TCs contain a confluent human endothelium grown atop a tri-dimensional human extracellular matrix substrate, employ human age-specific monocytes and autologous non heat-treated plasma, and avoid the use of xenogenic materials and exogenous cytokines. Vaccine-pulsed TCs autonomously generated DCs that induced single-antigen recall responses from autologous naïve and memory CD4+ T lymphocytes, matching study participant immune-status, including BCG responses paralleling donor PPD status, BCG-induced adenosine deaminase (ADA) activity paralleling infant cohorts in vivo, and multi-dose HBV antigen-specific responses as demonstrated by lymphoproliferation and TCR sequencing. Overall, our microphysiologic culture method reproduced age- and antigen-specific recall responses to BCG and HBV immunization, closely resembling those observed after a birth immunization of human cohorts in vivo, offering for the first time a new approach to early pre-clinical selection of effective age-targeted vaccine candidates.

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Perioperative Immunization for Splenectomy and the Surgeon’s Responsibility

2020

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plenectomy is a common operation, accounting for at least 25 000 procedures per year in the US. Indications include hematological diseases, traumatic injuries, and benign and malignant gastrointestinal, urological, and gynecologic conditions. The most dreadful sequel of splenectomy is overwhelming postsplenectomy infection (OPSI), a syndrome consisting of a nonspecific prodrome rapidly evolving toward pneumonia, meningitis, or fulminating sepsis. Although several strategies have been embraced, namely antibiotic prophylaxis, rescue therapy, and even splenic autotransplant, the cornerstone of OPSI prevention remains prophylactic immunization. Beyond the operating theater, surgeons play a determinant role in the care of patients who have had splenectomy. As the responsible physician in the immediate perioperative period, it is incumbent on them to first educate the patient regarding the nature of asplenic immunodeficiency and then prescribe appropriate immunization. Methods MEDLINE/PubMed, Cochrane Library, and ClinicalTrials.gov databases were searched for randomized clinical trials (RCTs) published from January 1, 1990, to December 31, 2019, addressing immunization in patients who had had splenectomy (eMethods in the Supplement). References of retrieved articles were searched manually, and current clinical guidelines were checked for further relevant literature. Research was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline methodology. 1 The research revealed 5 RCTs and 1 phase III nonrandomized trial (eFigure in the Supplement), Given the dearth of level I evidence focusing on the population of interest, results of systematic reviews, meta-analyses, and observational studies were also considered. Fi-IMPORTANCE Patients who have had splenectomy have a lifelong risk of overwhelming postsplenectomy infection (OPSI), a condition associated with high mortality rates. Surgeons must be aware of the rationale of vaccination in the case of splenectomy, to provide appropriate immunization in the perioperative time.OBSERVATIONS English-language articles published from January 1, 1990, to December 31, 2019, were retrieved from MEDLINE/PubMed, Cochrane Library, and ClinicalTrials.gov databases. Randomized clinical trials as well as systematic reviews and observational studies were considered. Asplenia yields an impairment of both innate and adaptive immunity, thus increasing the risk of severe encapsulated bacterial infections. Current epidemiology of OPSI ranges from 0.1% to 8.5% but is hard to ascertain because of ongoing shifts in patients' baseline conditions and vaccine penetration. Despite the lack of randomized clinical trials, immunization appears to be effective in reducing OPSI incidence. Unfortunately, vaccination coverage is still suboptimal, with a great variability in vaccination rates being reported across institutions and time frames. Notably, current guidelines do not advocate any particular health care qualification responsible for vac...

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Anti-Pneumococcal Vaccine-Induced Cellular Immune Responses in Post-Traumatic Splenectomized Individuals

Abstract: According to our data, splenectomy negatively influences the levels of PCV-induced lymphoproliferation, T1 differentiation, and cytokine release. Besides, PCV failed to induce T17-dominant immune response which is crucial for protection against extracellular pathogens.

Cited by 9 publications

References 39 publications

The effect of splenectomy on the levels of PCV-13-induced memory B- and T cells

The effect of splenectomy on the levels of PCV-13-induced memory B- and T cells

Microphysiologic Human Tissue Constructs Reproduce Autologous Age-Specific BCG and HBV Primary Immunization in vitro

Perioperative Immunization for Splenectomy and the Surgeon’s Responsibility

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