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Serological response to 13-valent pneumococcal conjugate vaccine in children and adolescents with perinatally acquired HIV infection.

ABSTRACT: Children with perinatally acquired HIV (paHIV) remain at an increased risk of pneumococcal infection despite highly active antiretroviral therapy (HAART). Beyond infancy, responses to pneumococcal conjugate vaccine (PCV) remain under-investigated. There are currently no published data on serological response to 13-valent PCV (PCV13) in the HIV-infected populations.We measured pneumococcal serotype-specific IgG in 48 paHIV-infected child patients (CP), 27 young adult healthy controls (AHC) and 30 child healthy controls (CHC). Opsonophagocytic assay (OPA) titres for three PCV13-exclusive serotypes were measured in a subset of children. Serotype-specific IgG was repeated 1 and 6 months following PCV13 vaccination of CP and AHC groups. OPA titres for four serotypes were measured at the 1-month time-point.The majority of CP, CHC and AHC had serotype-specific IgG above 0.35 ??g/ml at baseline, although OPA activity was undetectable for two of the three serotypes studied. Baseline IgG concentrations were significantly lower in CP than AHC for a proportion of serotypes and were strongly predictive of responses to vaccine. After adjusting for baseline, postvaccination IgG concentrations were comparable, although responses to some serotypes were impaired for CP. OPA correlated well with IgG after vaccination. Detectable HIV viral load was associated with significantly lower IgG concentration and OPA titre.Children with paHIV mount a robust serological response to PCV13 for most but not all vaccine serotypes. Viral load suppression with HAART and higher baseline IgG concentration are associated with higher postvaccination antibody levels. This has implications for HAART treatment and vaccination practices.

SUBMITTER: Bamford A

PROVIDER: S-EPMC4166014 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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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.

Project description:Importance:In several countries, 5 years after 13-valent pneumococcal conjugate vaccine (PCV13) implementation, serotype replacement has been reported for invasive pneumococcal disease, which raises concerns about the long-term outcome of PCV13 implementation. The long-term effect of vaccination on community-acquired pneumonia (CAP) remains unknown. Objective:To assess the long-term outcome of PCV13 implementation on CAP in children. Design, Setting, and Participants:This quasi-experimental, population-based, interrupted time-series analysis was based on a prospective multicenter study conducted from June 2009 to May 2017 in 8 French pediatric emergency departments. All patients 15 years and younger with chest radiography-confirmed CAP were included. Exposures:Community-acquired pneumonia. Main Outcomes and Measures:The number of CAP cases per 1000 pediatric emergency department visits over time, analyzed using a segmented regression model, adjusted for influenza-like illness syndromes. Results:We enrolled 12 587 children with CAP, including 673 cases of CAP with pleural effusion (5.3%), 4273 cases of CAP requiring hospitalization (33.9%), 2379 cases of CAP with high inflammatory biomarkers (18.9%), and 221 cases of proven pneumococcal CAP (1.8%). The implementation of PCV13 in 2010 was followed by a sharp decrease in the frequency of CAP (-0.8% per month [95% CI, -1.0% to -0.5% per month]), from 6.3 to 3.5 cases of CAP per 1000 pediatric emergency department visits until May 2014, then a slight increase since June 2014 (0.9% per month [95% CI, 0.4%-1.4% per month]), until 3.8 cases of CAP per 1000 pediatric emergency department visits in May 2017. There were marked immediate decreases in cases of CAP with pleural effusion (-48% [95% CI, -84% to -12%]), CAP requiring hospitalization (-30% [95% CI, -56% to -5%]), and CAP with high inflammatory biomarkers (-30% [95% CI, -54% to -6%]), without any rebound thereafter. Conclusions and Relevance:The changes associated with PCV13 use 7 years after implementation remain substantial, especially for CAP with pleural effusion, CAP requiring hospitalization, and CAP with high inflammatory biomarkers. Emerging non-PCV13 serotypes may be less likely involved in severe CAP than invasive pneumococcal disease.

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Serological response to 13-valent pneumococcal conjugate vaccine in children and adolescents with perinatally acquired HIV infection.

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