Dataset Information

Response to Pneumococcal Polysaccharide Vaccination in Newly Diagnosed HIV-Positive Individuals.

ABSTRACT: BACKGROUND:Newly diagnosed HIV-positive individuals are 35 to 100-fold more susceptible to Streptococcus pneumoniae infection compared to non-infected individuals. Therefore, the 23-valent pneumococcal polysaccharide vaccine (PPV23) has previously been recommended, though efficacy and effectiveness of vaccination remains controversial. Early severe B cell dysfunction is a central feature of HIV infection. The specific nature of the immune cells involved in the production of protective antigen-specific antibodies in HIV-positive individuals remains to be elucidated. OBJECTIVES:Evaluate the antibody and antigen-specific B cell response to the 23-valent pneumococcal polysaccharide vaccine in newly diagnosed HIV-positive patients. Moreover, determine if newly diagnosed patients with CD4<200 cells/?l benefit from 6-12 months of HAART, allowing partial viral suppression and immune reconstitution, prior to immunization. METHODS:Newly diagnosed HIV-positive patients with CD4>200 cells/?l and CD4<200 cells/?l were immunized with PPV23. Patients with CD4<200 cells/?l received either immediate or delayed immunization following 6-12 months of HAART. Antibody responses, opsonophagocytic activity and phenotypic analysis of pneumococcal polysaccharide-specific B cells were studied. RESULTS:Newly diagnosed HIV-positive patients demonstrated CD4-dependent increases in antibody and opsonophagocytic titers thought to be commensurate with protection. Functional opsonophagocytic titers of patients with CD4<200 cells/?l immunized immediately compared to patients with CD4<200 cells/?l receiving HAART for 6-12 months were not significantly different. Pneumococcal polysaccharide-specific B cells were distributed evenly between IgM memory and switched memory B cells for all groups, but IgM memory B cells were significantly lower than in HIV-negative individuals. CONCLUSIONS:Despite CD4-dependent pneumococcal polysaccharide-specific deficiencies in newly diagnosed HIV-positive patients, vaccination was beneficial based on opsonophagocytic titers for all newly diagnosed HIV-positive groups. In HIV-positive patients with CD4<200 cells/?l, 6-12 months of HAART did not improve opsonophagocytic titers or antibody concentrations. Based on these findings, immunization with the 23-valent pneumococcal polysaccharide vaccine should not be delayed in newly diagnosed HIV-positive patients with CD4<200 cells/?l.

SUBMITTER: Leggat DJ

PROVIDER: S-EPMC4405239 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Response to Pneumococcal Polysaccharide Vaccination in Newly Diagnosed HIV-Positive Individuals.

Leggat David J DJ Iyer Anita S AS Ohtola Jennifer A JA Kommoori Sneha S Duggan Joan M JM Georgescu Claudiu A CA Khuder Sadik A SA Khaskhely Noor M NM Westerink Ma Julie MJ

Journal of AIDS & clinical research 20150201 2

<h4>Background</h4>Newly diagnosed HIV-positive individuals are 35 to 100-fold more susceptible to <i>Streptococcus pneumoniae</i> infection compared to non-infected individuals. Therefore, the 23-valent pneumococcal polysaccharide vaccine (PPV23) has previously been recommended, though efficacy and effectiveness of vaccination remains controversial. Early severe B cell dysfunction is a central feature of HIV infection. The specific nature of the immune cells involved in the production of protec ...[more]

PMID: 25908995

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Project description:BackgroundDespite recommendations from the German Standing Committee on Vaccination (STIKO), pneumococcal vaccination coverage remains low in vulnerable populations. This study estimated the pneumococcal vaccination coverage rate (VCR) and timing among individuals aged 16-59 years in Germany who were recommended to receive pneumococcal vaccination, according to STIKO.MethodsA retrospective cohort analysis was conducted using the German InGef database. Individuals aged 16 to 59 years diagnosed with at least one "at-risk" (chronic disease) or "high-risk" (e.g., immunocompromising) condition considered to be at-risk of pneumococcal infection were identified at the time of first diagnosis, between January 1, 2016 and December 31, 2018, and followed up until December 31, 2019. The percentage of cumulative pneumococcal VCR with 95% confidence interval (CI) was reported for each calendar year of follow-up.ResultsThere were 334,292 individuals followed for a median of 2.38 (interquartile range (IQR) 1.63-3.13) person years. For individuals aged 16-59 years diagnosed with an incident risk condition in 2016, pneumococcal VCR increased from 0.44% (95% CI 0.41-0.48) in 2016 to 1.24% (95% CI 1.18-1.30) in 2019. In 2019, VCRs were higher in individuals with high-risk conditions compared with at-risk conditions (2.24% (95% CI 2.09-2.40) vs. 0.90% (95% CI 0.85-0.96)). In 2019, VCRs were higher in individuals aged 50 to 59 years compared with individuals aged 16 to 49 years (2.25% (95% CI 2.10-2.41) vs. 0.90% (95% CI 0.84-0.96)). Similar trends were observed in individuals with newly diagnosed risk conditions identified in 2017 and in 2018. Older age, influenza vaccination and increasing number of risk conditions increased the likelihood of pneumococcal vaccination. Median time to vaccination from diagnosis of the risk condition was shorter for high-risk conditions (369.5 days (IQR 155.8-702.0)) compared to at-risk conditions (435.5 days (IQR 196.3-758.8)).ConclusionDespite recommendations from STIKO, pneumococcal vaccination coverage remains very low and with long delays in vulnerable individuals aged 16-59 in Germany. Further efforts are required to increase immunization levels and shorten time to vaccination among individuals 16-59 years of age developing conditions with higher susceptibility to pneumococcal infection.

Project description:BackgroundBoth HIV positivity and African American (AA) ethnicity are associated with increased incidence of invasive pneumococcal disease (IPD). Poor immune response to pneumococcal polysaccharide-based vaccines may contribute to the race related increased frequency of IPD in African American HIV positive individuals.MethodsCaucasian and AA HIV-infected (HIV+) individuals 40-65 years old with CD4+ T cells/µl (CD4) >200 on antiretroviral therapy (ART) received either the 13-valent pneumococcal conjugate vaccine (PCV) followed by the 23-valent pneumococcal polysaccharide vaccine (PPV) or PPV only. Serum IgG, IgM and opsonophagocytic antibody responses to serotypes 14 and 23F as well as serum IgG and opsonophagocytic antibody responses to serotype 19A were measured pre- and post-vaccination. We measured serum markers of inflammation in all participants and performed single cell gene expression profiling at the baseline by HD Biomark in Caucasians and African Americans.ResultsThere were no significant differences in pre-immunization inflammatory markers or post-vaccination IgG and IgM concentrations between Caucasian and African American participants. However, we found significantly lower opsonophagocytic activity in response to serotypes 14 and 19A in the AA group compared to the Caucasian group. There was no association between inflammatory markers and immune response to vaccination, however we found extensive biomodal variation in gene expression levels in single IgM+ memory B cells. Differentially expressed genes may be related to differences in the immune response between ethnic groups.ConclusionsDistinct racial differences were found in the functional immune response following either PPV and/or PCV/PPV immunization in HIV-positive adults, although these differences were serotype dependent. Decreased ability to respond to vaccination may in part explain racial disparities in pneumococcal disease epidemiology. ClinicalTrials.gov ID: NCT03039491.

Project description:BackgroundMembers of the Tumor Necrosis Factor (TNF)-superfamily have speculated roles in the response against T-independent type II antigens (TI-II) including pneumococcal polysaccharides (PPS). Dysregulation in their expression is associated with an enhanced risk for pneumococcal disease in neonates but their expression in other high-risk populations including HIV-positive individuals remains to be elucidated.ObjectiveTo investigate signals that contribute towards PPS-response and identify potential anomalies that may account for diminished serological response in HIV-positive individuals post Pneumovax (PPV23) immunization.MethodsMarkers of inflammation, C-reactive protein (CRP), IL-6, sCD27 and sCD30, were assessed in HIV-positive and -negative individuals as potential predictors of PPV23 response. Serum levels of B cell activating factor (BAFF), transmembrane activator and calcium-modulator and cytophilin ligand interactor (TACI), B cell maturation antigen (BCMA) and B cell expression of BAFF-R, TACI, BCMA, CD40 and CD21 were assessed in total (unselected) and PPS23F (antigen)-specific B cells of PPV23 immunized HIV-positive and -negative individuals.ResultsCRP, sCD27, sCD30 and BAFF were significantly elevated in the serum of HIV-positive individuals but did not adversely affect PPV23 response. Assessment of PPS-specific B cells revealed enhanced TACI and reduced BAFF-R expression compared to unselected B cells in HIV-positive and -negative individuals. Surface TACI was similar but soluble TACI was significantly lower in HIV-positive compared to HIV-negative individuals.ConclusionCurrent studies highlight a potential role for TACI in PPV23 response based on its enhanced expression on PPS-specific B cells. Although surface levels of TACI were similar, diminished soluble TACI (sTACI) in HIV-positive compared to HIV-negative individuals could potentially decrease BAFF responsiveness and Ig response. A better understanding of the role of TNF receptors could contribute to the design of improved pneumococcal vaccines.Trial registrationClinicalTrials.gov NCT02515240.

Project description:There is today no gold standard method to accurately define the time passed since infection at HIV diagnosis. Infection timing and incidence measurement is however essential to better monitor the dynamics of local epidemics and the effect of prevention initiatives.Three methods for infection timing were evaluated using 237 serial samples from documented seroconversions and 566 cross sectional samples from newly diagnosed patients: identification of antibodies against the HIV p31 protein in INNO-LIA, SediaTM BED CEIA and SediaTM LAg-Avidity EIA. A multi-assay decision tree for infection timing was developed.Clear differences in recency window between BED CEIA, LAg-Avidity EIA and p31 antibody presence were observed with a switch from recent to long term infection a median of 169.5, 108.0 and 64.5 days after collection of the pre-seroconversion sample respectively. BED showed high reliability for identification of long term infections while LAg-Avidity is highly accurate for identification of recent infections. Using BED as initial assay to identify the long term infections and LAg-Avidity as a confirmatory assay for those classified as recent infection by BED, explores the strengths of both while reduces the workload. The short recency window of p31 antibodies allows to discriminate very early from early infections based on this marker. BED recent infection results not confirmed by LAg-Avidity are considered to reflect a period more distant from the infection time. False recency predictions in this group can be minimized by elimination of patients with a CD4 count of less than 100 cells/mm3 or without no p31 antibodies. For 566 cross sectional sample the outcome of the decision tree confirmed the infection timing based on the results of all 3 markers but reduced the overall cost from 13.2 USD to 5.2 USD per sample.A step-wise multi assay decision tree allows accurate timing of the HIV infection at diagnosis at affordable effort and cost and can be an important new tool in studies analyzing the dynamics of local epidemics or the effects of prevention strategies.

Project description:BackgroundThe objective of this systematic review and meta-analysis was to summarise the literature regarding the immunogenicity of pneumococcal conjugate vaccines (PCV) and pneumococcal polysaccharide vaccines (PPSV) in adult people living with HIV (PLWH) in the era of advanced combination antiretroviral therapy (cART).MethodsThe systematic review protocol was published online (PROSPERO ID: CRD 42020153137). We searched Medline (Ovid), EMBASE (Ovid), and the Global Health Library for publications from 2000 to June 11, 2020. We included all studies in adult PLWH that reported vaccine immunogenicity outcomes. The primary outcome was seroconversion rate (SCR) after PCV, PPSV and PCV/PPSV combined. For random-effects meta-analysis, we included studies defining SCR as a ≥ 2-fold increase in IgG from baseline, and reporting SCR for serotypes 6B, 14, or overall SCR, 1-3 months after vaccination.FindingsOur search identified 1597 unique studies, of which 115 were eligible for full-text assessment. Of these, 39 met the inclusion criteria (11 RCTs; 28 cohort studies). A high degree of heterogeneity was observed. Nineteen studies were included in the meta-analysis. Pooled overall SCRs were 42% (95% CI 30-56%), 44% (95% CI 33-55%) and 57% (95% CI 50-63%) for PLWH who received PPSV, PCV or a combination of PCV/PPSV, respectively. Compared to PPSV alone, a combination of PCV/PPSV yielded higher SCRs (OR 2.24 95% CI 1.41- 3.58), whereas we did not observe a significant difference in SCR between PCV and PPSV23 alone. There were no statistically significant differences in geometric mean post-vaccination antibody concentrations between vaccination schedules. Vaccination at higher CD4 cell counts improved immunogenicity in 8/21 studies, especially when PCV was administered. No studies assessed the long-term immunogenicity of PCV followed by PPSV23. Quality of evidence ranged from poor (n = 19) to good quality (n = 7). A limited number of pneumococcal serotypes was assessed in the majority of studies.InterpretationWe show that the recommended immunisation schedule consisting of a combination of PCV13/PPSV23, is immunogenic in PLWH in the era of advanced cART. However, the durability of this vaccination schedule remains unknown and must be addressed in future research. Vaccination with PCV should be delayed until immunological recovery (CD4>200) in recently diagnosed PLWH for optimal immunogenicity. The evidence gathered here supports wide implementation of the combination of PCV/PPSV23 for all PLWH. We recommend reassessment of this strategy once higher-valent PCVs become available.FundingHMGG is funded by a public research grant of ZonMw (project number 522004005).

Dataset Information

Response to Pneumococcal Polysaccharide Vaccination in Newly Diagnosed HIV-Positive Individuals.

Publications

Response to Pneumococcal Polysaccharide Vaccination in Newly Diagnosed HIV-Positive Individuals.

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