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Divergent humoral responses to 23-valent pneumococcal polysaccharide vaccine in critically-ill burn and neurosurgical patients.

ABSTRACT: Critically ill hospitalized patients are at increased risk of infection so we assessed the immunogenicity of 23-valent pneumococcal polysaccharide vaccine (PPSV23) administered within six days of injury.This prospective observational study compared the immunogenicity of PPSV23 among critically ill burn and neurosurgical patients at a tertiary, academic medical center. Patients received PPSV23 vaccination within six days of ICU admission per standard of care. Consent was obtained to measure concentrations of vaccine-specific IgG to 14 of 23 serotype capsule-specific IgG in serum prior to and 14-35 days following PPSV23. A successful immunologic response was defined as both a ?2-fold rise in capsule-specific IgG from baseline and concentrations of >1 mcg/mL to 10 of 14 measured vaccine serotypes. Immunologic response was compared between burn and neurosurgical patients. Multiple variable regression methods were used to explore associations of clinical and laboratory parameters to immunologic responses.Among the 16 burn and 27 neurosurgical patients enrolled, 87.5% and 40.7% generated a successful response to the vaccine, respectively (p = 0.004). Both median post-PPSV23 IgG concentrations (7.79 [4.56-18.1] versus 2.93 [1.49-8.01] mcg/mL; p = 0.006) and fold rises (10.66 [7.44-14.56] versus 3.48 [1.13-6.59]; p<0.001) were significantly greater in burn compared with neurosurgical patients. Presence of burn injury was directly and days from injury to immunization were inversely correlated with successful immunologic response (both p<0.03). Burn injury was associated with both increased median antibody levels post-PPSV23 and fold rise to 14 vaccine serotypes (p<0.03), whereas absolute lymphocyte count was inversely correlated with median antibody concentrations (p = 0.034).Critically ill burn patients can generate successful responses to PPSV23 during acute injury whereas responses among neurosurgical patients is comparatively blunted. Further study is needed to elucidate the mechanisms of differential antigen responsiveness in these populations, including the role of acute stress responses, as well as the durability of these antibody responses.

SUBMITTER: Mueller SW

PROVIDER: S-EPMC5951595 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Divergent humoral responses to 23-valent pneumococcal polysaccharide vaccine in critically-ill burn and neurosurgical patients.

Mueller Scott W SW Baumgartner Laura J LJ MacLaren Rob R Neumann Robert R Wiktor Arek J AJ Kiser Tyree H TH Lindberg Gordon G Cava Luis L Fish Douglas N DN Janoff Edward N EN

PloS one 20180514 5

<h4>Introduction</h4>Critically ill hospitalized patients are at increased risk of infection so we assessed the immunogenicity of 23-valent pneumococcal polysaccharide vaccine (PPSV23) administered within six days of injury.<h4>Methods</h4>This prospective observational study compared the immunogenicity of PPSV23 among critically ill burn and neurosurgical patients at a tertiary, academic medical center. Patients received PPSV23 vaccination within six days of ICU admission per standard of care. ...[more]

PMID: 29758059

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Project description:BACKGROUND:The immunomodulatory effects of statins on vaccine response remain uncertain. Therefore, the objective of this study was to determine if atorvastatin enhances pneumococcal-specific antibody titer following 23-valent pneumococcal polysaccharide vaccination. METHODS:Double-blind, placebo-controlled, single-center randomized clinical trial entitled StatVax. Subjects were enrolled between June and July 2014 and followed up through September 2014. 33 healthy volunteers signed informed consent after volunteer sampling. 11 participants were excluded; 22 healthy volunteers without prior pneumococcal vaccination were enrolled and completed the study. Participants were randomized to receive a 28-day course of 40 mg atorvastatin (n = 12) or matching lactose placebo (n = 10). On day 7 of treatment, Pneumovax 23 was administered intramuscularly. The primary outcome was fold change in total pneumococcal-specific antibody titer determined by a ratio of post-vaccination titer over baseline titer. Secondary outcomes included serotype-specific pneumococcal antibody titer, seroconversion, complete blood counts (CBC), erythrocyte sedimentation rate (ESR), and serum cytokine analysis. RESULTS:Of the 22 randomized patients (mean age, 23.86; SD, 4.121; 11 women [50%]), 22 completed the trial. Total anti-pneumococcal antibody titer in the atorvastatin group went from a baseline mean of 32.58 (SD, 15.96) to 147.7 (SD, 71.52) μg/mL at 21 days post-vaccination while titer in the placebo group went from a mean of 30.81 (SD, 13.04) to 104.4 (SD, 45) μg/mL. When comparing fold change between treatment groups, there was a significant increase in fold change of total anti-pneumococcal antibody titer in the atorvastatin group compared to the placebo group (2-way ANOVA, p = .0177). CONCLUSIONS:Atorvastatin enhances antigen-specific primary humoral immune response to a T cell-independent pneumonia vaccination. Pending confirmation by larger cohort studies of target populations, peri-vaccination conventional doses of statins can become a novel adjuvant for poorly-immunogenic polysaccharide-based vaccines. TRIAL REGISTRATION:clinicaltrials.gov Identifier: NCT02097589.

Project description:IntroductionLong-term comparative immunologic response to 13-valent pneumococcal conjugate vaccine (PCV13) versus 23-valent polysaccharide vaccine (PPV23) among HIV-infected adults has not yet been investigated.MethodsIn this prospective pilot study, we quantified in HIV-positive adults serotype-specific IgG concentrations of the 12 pneumococcal serotypes shared by both vaccines 5 years after vaccination with two doses of PCV13 8 weeks apart (group 1) or one dose of PPV23 (group 2) and compared them with those assessed prior to vaccination (BL) and after 1 year (T1). Comparison of immunogenicity was based on geometric mean concentration (GMC), proportion of individuals with ≥ twofold increase from BL in specific antibody concentration against ≥ 2 serotypes and percentage of individuals with serotype-specific IgG ≥ 0.35 μg/ml, ≥ 1 μg/ml and ≥ individual serotype-specific correlates of protection.ResultsWe included 91 subjects (median CD4+ 650 cells/µl, > 90% with HIV-RNA < 50 copies/ml); patients in groups 1 (n = 42) and 2 (n = 49) were homogeneous for the main characteristics. GMCs were significantly higher in the PCV13 group than in the PPV23 group for serotype 19F (p = 0.003). Both vaccines revealed higher significant GMCs to most serotypes compared with BL, i.e., eight in group 1 vs. seven in group 2. With respect to T1, GMCs decreased significantly in the PCV13 group for eight vs. ten serotypes in the PPV23 group. More participants in the PCV13 group had ≥ 2 increase from BL in antibody levels to ≥ 2 serotypes compared with the PPV23 group (78.6% vs. 59.2%, p = 0.042). Overall, the percentage of subjects with serotype-specific IgG ≥ 0.35 μg/ml, ≥ 1 μg/ml and ≥ individual serotype-specific correlates of protection was similar between groups.ConclusionIn this study with HIV-positive adults with a favorable viro-immunologic profile, both vaccines were shown to achieve a long-term durable serologic response. We found minor differences in immunogenicity between the two vaccines, which favored PCV13 over PPV23 5 years after immunization.Trial registrationClinicalTrials.gov identifier, NCT02123433.

Dataset Information

Divergent humoral responses to 23-valent pneumococcal polysaccharide vaccine in critically-ill burn and neurosurgical patients.

Publications

Divergent humoral responses to 23-valent pneumococcal polysaccharide vaccine in critically-ill burn and neurosurgical patients.

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