Long-term immune responses to vaccination in HIV-infected patients: a systematic review and meta-analysis.
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ABSTRACT:
SUBMITTER: Kerneis S
PROVIDER: S-EPMC4761378 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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).
| S-EPMC7695973 | biostudies-literature
Project description:IntroductionResponses to SARS-CoV-2 vaccination in patients with MS (pwMS) varies by disease-modifying therapies (DMTs). We perform a meta-analysis and systematic review of immune response to SARS-CoV-2 vaccines in pwMS.MethodsTwo independent reviewers searched PubMed, Google Scholar, and Embase from January 1, 2019-December 31, 2021, excluding prior SARS-CoV-2 infections. The meta-analysis of observational studies in epidemiology (MOOSE) guidelines were applied. The data were pooled using a fixed-effects model.ResultsEight-hundred sixty-four healthy controls and 2203 pwMS from 31 studies were included. Antibodies were detected in 93% healthy controls (HCs), and 77% pwMS, with >93% responses in all DMTs (interferon-beta, glatiramer acetate, cladribine, natalizumab, dimethyl fumarate, alemtuzumab, and teriflunomide) except for 72% sphingosine-1-phosphate modulators (S1PM) and 44% anti-CD20 monoclonal antibodies (mAbs). T-cell responses were detected in most anti-CD20 and decreased in S1PM. Higher antibody response was observed in mRNA vaccines (99.7% HCs) versus non-mRNA vaccines (HCs: 72% inactivated virus; pwMS: 86% vector, 59% inactivated virus). A multivariate logistic regression model to predict vaccine response demonstrated that mRNA versus non-mRNA vaccines had a 3.4 odds ratio (OR) for developing immunity in anti-CD20 (p = 0.0052) and 7.9 OR in pwMS on S1PM or CD20 mAbs (p < 0.0001). Antibody testing timing did not affect antibody detection.ConclusionAntibody responses are decreased in S1PM and anti-CD20; however, cellular responses were positive in most anti-CD20 with decreased T cell responses in S1PM. mRNA vaccines had increased seroconversion rates compared to non-RNA vaccines. Further investigation in how DMTs affect vaccine immunity are needed.
| S-EPMC9349877 | biostudies-literature
Project description:The prophylactic vaccines available to protect against infections by HPV are well tolerated and highly immunogenic. People with HIV have a higher risk of developing HPV infection and HPV-associated cancers due to a lower immune response, and due to viral interactions. We performed a systematic review of RCTs to assess HPV vaccines efficacy and safety on HIV-infected people compared to placebo or no intervention in terms of seroconversion, infections, neoplasms, adverse events, CD4+ T-cell count and HIV viral load. The vaccine-group showed a seroconversion rate close to 100% for each vaccine and a significantly higher level of antibodies against HPV vaccine types, as compared to the placebo group (MD = 4333.3, 95% CI 2701.4; 5965.1 GMT EL.U./ml for HPV type 16 and MD = 1408.8, 95% CI 414.8; 2394.7 GMT EL.U./ml for HPV type 18). There were also no differences in terms of severe adverse events (RR = 0.6, 95% CI 0.2; 1.6) and no severe adverse events (RR = 0.6, 95% CI 0.9; 1.2) between vaccine and placebo groups. Secondary outcomes, such as CD4 + T-cell count and HIV viral load, did not differ between groups (MD = 14.8, 95% CI - 35.1; 64.6 cells/µl and MD = 0.0, 95% CI - 0.3; 0.3 log10 RNA copies/ml, respectively). Information on the remaining outcomes was scarce and that did not allow us to combine the data. The results support the use of the HPV vaccine in HIV-infected patients and highlight the need of further RCTs assessing the effectiveness of the HPV vaccine on infections and neoplasms.
| S-EPMC7925667 | biostudies-literature
Project description:BackgroundHIV-infected and HIV-exposed uninfected (HEU) children have an increased risk of measles that may be due to altered immune responses or suboptimal timing of measles vaccination. We aimed to evaluate the safety and immunogenicity of measles vaccination in HIV-infected and HEU children.MethodsFor this systematic review and meta-analysis, we searched PubMed, Embase, Cochrane Library, CINAHL, Global Health Library and IndMED on May 9, 2018. Studies were included if they reported on safety or seroresponse (either seroprotection/seropositivity/seroconversion) after measles vaccination in HIV-infected or HEU children. We calculated pooled estimates to compare immunogenicity outcomes between HIV-infected, HEU and HIV-unexposed children, using risk ratios [RRs] (with 95%CIs). PROSPERO registration number: CRD42017057411.FindingsSeventy-one studies met the inclusion criteria (15,363 children). Twenty-eight studies reported on safety; vaccine-associated adverse events and deaths were uncommon. Sixty-two studies reported on immunogenicity, 27 were included in the meta-analysis. HIV-infected children had lower seroresponse rates after primary vaccination compared with HIV-unexposed (RR 0.74; 95%CI: 0.61-0.90, I 2 ?=?85.9%) and HEU children (0.78; 0.69-0.88, I 2 ?=?77.1%), which was mitigated by antiretroviral therapy and time interval between vaccination and serology. HEU and HIV-unexposed children had similar seroresponses. Vaccination at 6-months resulted in similar proportions of HIV-infected children having seroresponse compared with HIV-unexposed (0.96; 0.77-1.19) and HEU children (1.00; 0.73-1.37, I 2 ?=?63.7%).InterpretationPrimary measles vaccination at 6-months of age may provide protection against measles during early infancy in settings with high prevalence of maternal HIV-infection, however, further studies are needed to evaluate this strategy in HEU children and HIV-infected children receiving antiretroviral therapy.FundingSouth African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation in Vaccine Preventable Diseases; Medical Research Council: Respiratory and Meningeal Pathogens Research Unit.
| S-EPMC6537570 | biostudies-literature
Project description:Adjuvanted-influenza vaccination is an efficient method for enhancing the immunogenicity of influenza split-virus vaccines for preventing influenza. However, the medical community's understanding of its performance in patients infected with HIV remains limited. To identify the advantages, we conducted a systematic review and meta-analysis with randomized controlled trials (RCTs) and cohort and case-control studies that have the immunogenicity and safety of influenza vaccines in patients infected with HIV as outcomes. We searched six different databases, and 1698 patients infected with HIV in 11 studies were included. Statistical analysis was performed to calculate the pooled standardized mean differences (SMD) or relative risk (RR) and 95% confidence interval (CI). Regarding immunogenicity, the pooled SMD of GMT (Geometric mean titer) for A/H1N1 was 0.61 (95%CI (0.40,0.82)), the pooled RR of seroconversion was 1.34 (95%CI (0.91,1.98)) for the H1N1 vaccine, 1.27(95%CI (0.64,2.52)) for the H3N2 vaccine, 1.19(95%CI (0.97,1.46)) for the B-type influenza vaccine. The pooled RR of seroprotection was 1.61 (95%CI (1.00,2.58)) for the H1N1 vaccine, 1.06 (95%CI(0.83,1.35)) for the H3N2 vaccine, and 1.13(95%CI(0.91,1.41)) for the B-type vaccine. Adjuvanted-influenza vaccination showed good general tolerability in patients infected with HIV, with the only significant increase being the rate of local pain at the injection site (RR = 2.03, 95%CI (1.06,3.86)). In conclusion, all studies evaluating injected adjuvanted influenza vaccination among patients infected with HIV showed acceptable levels of safety and immunogenicity.
| S-EPMC7227622 | biostudies-literature
Project description:Interventions: A patient is vaccinated with Montanide ISA51-adjuvanted WT1 Trio cancer vaccine consisting of two WT1 CTL peptides (WT1-126 and WT1-235) and one WT1 HTL peptide (WT1-332) (2mg each) seven times at the interval of two to four weeks. The interval can be changed within a range from one to 16 weeks.
Primary outcome(s): Induction of WT1-specific immune responses assessed by WT1-related tests such as WT1-DTH skin reaction, serum levels of WT1 peptide IgG autoantibody, and frequency of WT1-CTL in PB * This is evaluated at the interval ranging from 6 to 12 months.
Study Design: Single arm Non-randomized
| 2638831 | ecrin-mdr-crc
Project description:BackgroundTo access the long term relationship between efavirenz plasma concentrations and evolution of HIV RNA loads and CD4 cell counts in children.MethodsRetrospective analysis of data from HIV-infected children on first line efavirenz-containing regimen. A population pharmacokinetic-pharmacodynamic (PK-PD) model was developed to describe the evolution of HIV RNA load and CD4 cell count (efficacy outcomes) in relation to efavirenz plasma concentration. Individual CYP2B6 516 G>T genotype data were not available for this analysis. A score (ISEFV) quantifying the effect of efavirenz concentrations on the long-term HIV replication was calculated from efavirenz concentrations and PD parameters and, a value of ISEFV below which HIV replication is likely not suppressed was determined. Cox proportional hazards regression models were used to assess the association of the risk of viral replication with ISEFV, and with efavirenz mid-dose concentration(C12).ResultsAt treatment initiation, median (interquartile range, IQR) age was 8 years (5 to 10), body weight 17 kg (14 to 23), HIV RNA load 5.1 log10 copies/mL (4.6 to 5.4), and CD4 cell count 71 cells/mm3. A model of PK-PD viral dynamics assuming that efavirenz decreases the rate of infected host cells adequately described the relationship of interest. After adjusting for age, baseline HIV RNA load and CD4 cell counts an ISEFV <85% was significantly associated with a higher risk of viral replication (p-value <0.001) while no significant association was observed with C12 <1.0 mg/L.ConclusionThe ISEFV score was a good predictor of viral replication in children on efavirenz-based treatment.
| S-EPMC6521995 | biostudies-literature
Project description:We have investigated the ability of hepatitis C virus non-structural (NS) 3/4A-DNA-based vaccines to activate long-term cell-mediated immune responses in mice. Wild-type and synthetic codon optimized (co) NS3/4A DNA vaccines have previously been shown to be immunogenic in mice, rabbits and humans, although we have very poor knowledge about the longevity of the immune responses primed. We therefore analyzed the functionality of primed NS3/4A-specific immune responses in BALB/c (H-2(d)) and/or C57BL/6J (H-2(b)) mice 1, 2, 3, 4, 6, 12 and 16 months after the last immunization. Mice were immunized one, two, three or four times using gene gun delivery to the skin or by intramuscular administration. Immunological responses after immunization were monitored by protection against in vivo challenge of NS3/4A-expressing syngeneic tumor cells. In addition, functionality of the NS3/4A-specific T cells was analyzed by a standard cytotoxicity assay. First, we identified a new unique murine H-2(d)-restricted NS3/4A cytotoxic T lymphocyte (CTL) epitope, which enabled us to study the epitope-specific immune responses. Our results show that the coNS3/4A vaccine was highly immunogenic by determination of interferon-?/tumor necrosis factor-? production and lytic cytotoxic T cells, which could efficiently inhibit in vivo tumor growth. Importantly, we showed that one to four monthly immunizations protected mice from tumor development when challenged up to 16 months after the last immunization. When determining the functionality of NS3/4A-specific T cells in vitro, we showed detectable lytic activity up to 12 months after the last immunization. Thus, NS3/4A-based DNA vaccines activate potent cellular immune responses that are present and function in both BALB/c and C57BL/6J mice up to 12-16 months after the last immunization. The induction of long-term immunity after NS3/4A DNA immunization has not been shown previously and supports the use of NS3/4A in hepatitis C virus vaccine compositions.
| S-EPMC4126484 | biostudies-literature
Project description:Background: Disease progression monitoring through CD4 counts alone can be inadequate in HIV infection as ongoing immune activation may result in Serious non-AIDS events (SNAEs). SNAEs involve monocyte activation driven chronic inflammation with significant sequelae observed even during HAART. Here, we attempted to delineate functional monocyte based signatures across stages of HIV disease progression. Methods: Participants spanning four cohorts were recruited-pre-ART (PA; <7 years of infection; n = 20), long-term non-progressors (LTNP; >7 years of infection, CD4 > 350 cells/μL, n = 20), individuals on therapy (ART; n = 18) and seronegative controls (SN; n = 15). Immunophenotyping of monocyte subsets and evaluation of expression of HIV-binding receptors-CD4 and CCR5, marker of immune activation- HLA-DR and M2 phenotype-mannose receptor (CD206) was followed by association of monocyte-specific parameters with conventional markers of disease progression such as absolute CD4 count, CD4/CD8 ratio, viral load, and T cell activation. Results: A significant expansion of intermediate monocytes (CD14++CD16+) with a concomitant decline in classical subset (CD14++CD16-) was observed in all infected cohorts compared to seronegative controls. In addition, an expansion of the non-classical subset (CD14+CD16++) was observed in long-term non-progressors. Dysregulation in monocyte subsets associated with CD4 count and CD4/CD8 ratio in PAs but not in LTNPs. We report for the first time that expression of CD206 is most prominent on intermediate monocytes which also have the highest expression of CD4, CCR5, and HLA-DR. Despite preserved CD4 counts, LTNPs had similar immune activation profiles to PAs, as evidenced by elevated HLA-DR expression across monocyte subsets. HLA-DR expression, similar to that in SNs, observed in the ART group indicated partial immune restoration within the monocyte compartment. Increased CD206 expression on monocytes together with frequency of activated CD4+ T lymphocytes (HLA-DR+CD38+) showed significant and positive association with viral load in LTNPs, but not PAs. Conclusion: Our results describe for the first time the presence of monocyte dysregulation involving increased activation in LTNPs, who, in spite of preserved CD4 counts, may remain susceptible to prolonged effects of systemic inflammation and highlight CD206, as a unique non-T correlate of viremia, in viremic non-progression.
| S-EPMC6908494 | biostudies-literature
Project description:The effective protective HIV vaccine should elicit either protective antibodies or effective T cell response, or both. To improve the efficacy of HIV-1 vaccines, HLA polymorphism and HIV-1 diversity are 2 key factors to be considered for vaccine development. In this study, we expressed a recombinant multi-epitope protein MEP1 which has the same amino acid sequence as a DNA vaccine for Chinese population in our previous report. We found that MEP1 alone could elicit moderate levels of humoral and cellular immune responses, but these responses could not provide protection from challenge with a recombinant virus rTTV-lucgag, which expresses Gag of HIV-1 CRF_07BC. Nevertheless, when MEP1 was immunized with aluminum adjuvant, both humoral and cellular immune responses were significantly increased, and they were protective against virus infection; meanwhile, MEP1 with aluminum not only elicited early (10 d post immunization) but also a long-term (at least 44 weeks post immunization) immune responses in BALB/c mice. These results suggested that MEP1 has the potential to be developed as an effective vaccine candidate, and that suitable adjuvant is necessary for this protein to generate protective immune responses.
| S-EPMC5489306 | biostudies-other