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Marcos Da Silva Freire - One of the best experts on this subject based on the ideXlab platform.
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cd4 cd8 ratio and kt ratio predict Yellow Fever Vaccine immunogenicity in hiv infected patients
PLOS Neglected Tropical Diseases, 2016Co-Authors: Vivian Iida Avelinosilva, Peter W Hunt, Yong Huang, Marisol Simoes, Marisa A Hong, Karina Takesaki Miyaji, Sheila Maria Barbosa De Lima, Marcos Da Silva Freire, Helio H CaiaffafilhoAbstract:Author(s): Avelino-Silva, Vivian I; Miyaji, Karina T; Hunt, Peter W; Huang, Yong; Simoes, Marisol; Lima, Sheila B; Freire, Marcos S; Caiaffa-Filho, Helio H; Hong, Marisa A; Costa, Dayane Alves; Dias, Juliana Zanatta C; Cerqueira, Natalia B; Nishiya, Anna Shoko; Sabino, Ester Cerdeira; Sartori, Ana M; Kallas, Esper G | Abstract: BackgroundHIV-infected individuals have deficient responses to Yellow Fever Vaccine (YFV) and may be at higher risk for adverse events (AE). Chronic immune activation-characterized by low CD4/CD8 ratio or high indoleamine 2,3-dioxygenase-1 (IDO) activity-may influence Vaccine response in this population.MethodsWe prospectively assessed AE, viremia by the YFV virus and YF-specific neutralizing antibodies (NAb) in HIV-infected (CD4g350) and -uninfected adults through 1 year after vaccination. The effect of HIV status on initial antibody response to YFV was measured during the first 3 months following vaccination, while the effect on persistence of antibody response was measured one year following vaccination. We explored CD4/CD8 ratio, IDO activity (plasma kynurenine/tryptophan [KT] ratio) and viremia by Human Pegivirus as potential predictors of NAb response to YFV among HIV-infected participants with linear mixed models.Results12 HIV-infected and 45-uninfected participants were included in the final analysis. HIV was not significantly associated with AE, YFV viremia or NAb titers through the first 3 months following vaccination. However, HIV-infected participants had 0.32 times the NAb titers observed for HIV-uninfected participants at 1 year following YFV (95% CI 0.13 to 0.83, p = 0.021), independent of sex, age and prior vaccination. In HIV-infected participants, each 10% increase in CD4/CD8 ratio predicted a mean 21% higher post-baseline YFV Nab titer (p = 0.024). Similarly, each 10% increase in KT ratio predicted a mean 21% lower post-baseline YFV Nab titer (p = 0.009). Viremia by Human Pegivirus was not significantly associated with NAb titers.ConclusionsHIV infection appears to decrease the durability of NAb responses to YFV, an effect that may be predicted by lower CD4/CD8 ratio or higher KT ratio.
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cd4 cd8 ratio predicts Yellow Fever Vaccine induced antibody titers in virologically suppressed hiv infected patients
Journal of Acquired Immune Deficiency Syndromes, 2016Co-Authors: Vivian Iida Avelinosilva, Marisol Simoes, Dayane Alves Costa, Karina Takesaki Miyaji, Augusto Mathias, Juliana Zanatta De Carvalho Dias, Sheila Maria Barbosa De Lima, Marcos Da Silva Freire, Helio H Caiaffafilho, Marisa A HongAbstract:BACKGROUND: Yellow Fever Vaccine (YFV) induces weaker immune responses in HIV-infected individuals. However, little is known about YFV responses among antiretroviral-treated patients and potential immunological predictors of YFV response in this population. METHODS: We enrolled 34 antiretroviral therapy (ART)-treated HIV-infected and 58 HIV-uninfected adults who received a single YFV dose to evaluate antibody levels and predictors of immunity, focusing on CD4(+) T-cell count, CD4(+)/CD8(+) ratio, and Human Pegivirus (GBV-C) viremia. Participants with other immunosuppressive conditions were excluded. RESULTS: Median time since YFV was nonsignificantly shorter in HIV-infected participants than in HIV-uninfected participants (42 and 69 months, respectively, P = 0.16). Mean neutralizing antibody (NAb) titers was lower in HIV-infected participants than HIV-uninfected participants (3.3 vs. 3.6 log10mIU/mL, P = 0.044), a difference that remained significant after adjustment for age, sex, and time since vaccination (P = 0.024). In HIV-infected participants, lower NAb titers were associated with longer time since YFV (rho: -0.38, P = 0.027) and lower CD4(+)/CD8(+) ratio (rho: 0.42, P = 0.014), but not CD4(+) T-cell count (P = 0.52). None of these factors were associated with NAb titers in HIV-uninfected participant. GBV-C viremia was not associated with difference in NAb titers overall or among HIV-infected participants. CONCLUSIONS: ART-treated HIV-infected individuals seem to have impaired and/or less durable responses to YFV than HIV-uninfected individuals, which were associated with lower CD4(+)/CD8(+) ratio, but not with CD4(+) T-cell count. These results supports the notion that low CD4(+)/CD8(+) ratio, a marker linked to persistent immune activation, is a better indicator of functional immune disturbance than CD4(+) T-cell count in patients with successful ART.
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subdoses of 17dd Yellow Fever Vaccine elicit equivalent virological immunological kinetics timeline
BMC Infectious Diseases, 2014Co-Authors: Ana Carolina Campiazevedo, Maria De Lourdes De Sousa Maia, Roberto Henrique Guedes Farias, Paula De Almeida Estevam, Jordana Grazziela Coelhodosreis, Vanessa Peruhypemagalhaes, Gabriela Villelarezende, Patricia Flavia Quaresma, Luiz Henrique Guedes Camacho, Marcos Da Silva FreireAbstract:Background: The live attenuated 17DD Yellow Fever Vaccine is one of the most successful prophylactic interventions for controlling disease expansion ever designed and utilized in larger scale. However, increase on worldwide Vaccine demands and manufacturing restrictions urge for more detailed dose sparing studies. The establishment of complementary biomarkers in addition to PRNT and Viremia could support a secure decision-making regarding the use of 17DD YF Vaccine subdoses. The present work aimed at comparing the serum chemokine and cytokine kinetics triggered by five subdoses of 17DD YF Vaccine. Methods: Neutralizing antibody titers, viremia, cytokines and chemokines were tested on blood samples obtained from eligible primary Vaccinees. Results and discussion: The results demonstrated that a fifty-fold lower dose of 17DD-YF Vaccine (587 IU) is able to trigger similar immunogenicity, as evidenced by significant titers of anti-YF PRNT. However, only subdoses as low as 3,013 IU elicit viremia kinetics with an early peak at five days after primary vaccination equivalent to the current dose (27,476 IU), while other subdoses show a distinct, lower in magnitude and later peak at day 6 post-vaccination. Although the subdose of 587 IU is able to trigger equivalent kinetics of IL-8/CXCL-8 and MCP-1/CCL-2, only the subdose of 3,013 IU is able to trigger similar kinetics of MIG/CXCL-9, pro-inflammatory (TNF, IFN-γ and IL-2) and modulatory cytokines (IL-5 and IL-10). Conclusions: The analysis of serum biomarkers IFN-γ and IL-10, in association to PRNT and viremia, support the recommendation of use of a ten-fold lower subdose (3,013 IU) of 17DD-YF Vaccine.
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17dd Yellow Fever Vaccine a double blind randomized clinical trial of immunogenicity and safety on a dose response study
Human Vaccines & Immunotherapeutics, 2013Co-Authors: Reinaldo De Menezes Martins, Sheila Maria Barbosa De Lima, Marcos Da Silva Freire, Maria De Lourdes De Sousa Maia, Luiz Antonio Bastos Camacho, Roberto Henrique Guedes Farias, Anna M Y Yamamura, Ricardo Galler, L F C Almeida, Rita Maria Ribeiro NogueiraAbstract:Objective: To verify if the Bio-Manguinhos 17DD Yellow Fever Vaccine (17DD-YFV) used in lower doses is as immunogenic and safe as the current formulation.Results: Doses from 27,476 IU to 587 IU ind...
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17dd Yellow Fever Vaccine a double blind randomized clinical trial of immunogenicity and safety on a dose response study
Human Vaccines & Immunotherapeutics, 2013Co-Authors: Reinaldo De Menezes Martins, Sheila Maria Barbosa De Lima, Marcos Da Silva Freire, Maria De Lourdes De Sousa Maia, Luiz Antonio Bastos Camacho, Roberto Henrique Guedes Farias, Anna M Y Yamamura, Ricardo Galler, L F C Almeida, Rita Maria Ribeiro NogueiraAbstract:Objective: To verify if the Bio-Manguinhos 17DD Yellow Fever Vaccine (17DD-YFV) used in lower doses is as immunogenic and safe as the current formulation. Results: Doses from 27,476 IU to 587 IU induced similar seroconversion rates and neutralizing antibodies geometric mean titers (GMTs). Immunity of those who seroconverted to YF was maintained for 10 mo. Reactogenicity was low for all groups. Methods: Young and healthy adult males (n = 900) were recruited and randomized into 6 groups, to receive deescalating doses of 17DD-YFV, from 27,476 IU to 31 IU. Blood samples were collected before vaccination (for neutralization tests to Yellow Fever, serology for dengue and clinical chemistry), 3 to 7 d after vaccination (for viremia and clinical chemistry) and 30 d after vaccination (for new Yellow Fever serology and clinical chemistry). Adverse events diaries were filled out by volunteers during 10 d after vaccination. Volunteers were retested for Yellow Fever and dengue antibodies 10 mo later. Seropositivity for dengue was found in 87.6% of volunteers before vaccination, but this had no significant influence on conclusions. Conclusion: In young healthy adults Bio-Manguinhos/Fiocruz Yellow Fever Vaccine can be used in much lower doses than usual.
Leo G Visser - One of the best experts on this subject based on the ideXlab platform.
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what s old is new again the re emergence of Yellow Fever in brazil and Vaccine shortages
Clinical Infectious Diseases, 2019Co-Authors: Phyllis E Kozarsky, Lin H Chen, Leo G VisserAbstract:Yellow Fever outbreaks have continued to occur and caused infection and deaths in travelers from non-endemic regions. Yellow Fever Vaccine has proven effective, but vaccination decisions require balancing benefits with risks. Of concern is the continued Vaccine shortage worldwide, including of the YF-VAX® stockout in North America, which has presented many challenges.
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17d Yellow Fever Vaccine elicits comparable long term immune responses in healthy individuals and immune compromised patients
Journal of Infection, 2016Co-Authors: Rosanne W Wieten, Leo G Visser, Abraham Goorhuis, Emile F F Jonker, G J De Bree, A W De Visser, P J J Van Genderen, Ester B M Remmerswaal, I Ten J M Berge, Martin P GrobuschAbstract:Summary Background The 17D live attenuated Yellow Fever (YF) Vaccine is contra-indicated in immune-compromised individuals and may elicit a suboptimal immunologic response. The aim of this study is to assess whether long-term immune responses against the YF Vaccine are impaired in immune-compromised patients. Materials and methods Fifteen patients using different immunosuppressive drugs and 30 healthy individuals vaccinated 0–22 years ago were included. The serological response was measured using the plaque reduction neutralization test (PRNT). CD8 + and CD4 + T-cell responses were measured following proliferation and re-stimulation with YFV peptide pools. Phenotypic characteristics and cytokine responses of CD8 + T-cells were determined using class I tetramers. Results The geometric mean titre of neutralizing antibodies was not different between the groups (p = 0.77). The presence of YFV-specific CD4 + and CD8 + T-cell did not differ between patients and healthy individuals (15/15, 100.0% vs. 29/30, 96.7%, p = 0.475). Time since vaccination correlated negatively with the number of YFV-specific CD8 + T-cells (r = −0.66, p = 0.0045). Percentages of early-differentiated memory cells increased (r = 0.67, p = 0.017) over time. Conclusion These results imply that YF vaccination is effective despite certain immunosuppressive drug regimens. An early-differentiated memory-like phenotype persisted, which is associated with effective expansion upon re-encounter with antigen, suggesting a potent memory T-cell pool remains.
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elderly subjects have a delayed antibody response and prolonged viraemia following Yellow Fever vaccination a prospective controlled cohort study
PLOS ONE, 2011Co-Authors: Anna H Roukens, Peter J Bredenbeek, Jaap T Van Dissel, Darius Soonawala, Simone A Joosten, Adriette W De Visser, Xiaohong Jiang, Kees Dirksen, Marjolein De Gruijter, Leo G VisserAbstract:Background Yellow Fever vaccination (YF-17D) can cause serious adverse events (SAEs). The mechanism of these SAEs is poorly understood. Older age has been identified as a risk factor. We tested the hypothesis that the humoral immune response to Yellow Fever Vaccine develops more slowly in elderly than in younger subjects. Method We vaccinated young volunteers (18–28 yrs, N = 30) and elderly travelers (60–81 yrs, N = 28) with YF-17D and measured their neutralizing antibody titers and plasma YF-17D RNA copy numbers before vaccination and 3, 5, 10, 14 and 28 days after vaccination. Results Ten days after vaccination seroprotection was attained by 77% (23/30) of the young participants and by 50% (14/28) of the elderly participants (p = 0.03). Accordingly, the Geometric Mean Titer of younger participants was higher than the GMT of the elderly participants. At day 10 the difference was +2.9 IU/ml (95% CI 1.8–4.7, p = 0.00004) and at day 14 +1.8 IU/ml (95% CI 1.1–2.9, p = 0.02, using a mixed linear model. Viraemia was more common in the elderly (86%, 24/28) than in the younger participants (60%, 14/30) (p = 0.03) with higher YF-17D RNA copy numbers in the elderly participants. Conclusions We found that elderly subjects had a delayed antibody response and higher viraemia levels after Yellow Fever primovaccination. We postulate that with older age, a weaker immune response to Yellow Fever Vaccine allows the attenuated virus to cause higher viraemia levels which may increase the risk of developing SAEs. This may be one piece in the puzzle of the pathophysiology of YEL-AVD. Trial Registration Trialregitser.nl NTR1040
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reduced intradermal test dose of Yellow Fever Vaccine induces protective immunity in individuals with egg allergy
Vaccine, 2009Co-Authors: Anna H Roukens, Ann C T M Vossen, Jaap T Van Dissel, Leo G VisserAbstract:The neutralising antibody response after the Yellow Fever Vaccine (YF-17D) skin test was measured in 7 egg allergic persons in whom further vaccination was abandoned because of a strong local urticarial reaction to the YF-17D Vaccine test dose. We found that this test dose of 0.1 mL of YF-17D Vaccine was sufficient to induce a protective antibody response in all 7 subjects. Intradermal injection of 1/5th dose of the Yellow Fever Vaccine appears to be sufficient, in non-allergic as well as allergic persons, and non-inferior to the subcutaneous full dose.
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intradermally administered Yellow Fever Vaccine at reduced dose induces a protective immune response a randomized controlled non inferiority trial
PLOS ONE, 2008Co-Authors: Anna H Roukens, Peter J Bredenbeek, Ann C T M Vossen, Jaap T Van Dissel, Leo G VisserAbstract:textabstractBackground:Implementation of Yellow Fever vaccination is currently hampered by limited supply of Vaccine. An alternative route of administration with reduced amounts of Vaccine but without loss of Vaccine efficacy would boost vaccination programmes.Methods and Findings:A randomized, controlled, non-inferiority trial was conducted in a Dutch university center between August 2005 and February 2007. A total of 155 primary vaccinated and 20 previously vaccinated volunteers participated. Participants were randomly assigned in a 1:1 ratio to receive intradermal (i.d.) vaccination with live attenuated Yellow Fever 17D Vaccine at a reduced dose (1/5th; 0·1 mL) or the conventional subcutaneous (s.c.) vaccination (0·5 mL). Antibody neutralization titers were determined at 2, 4 and 8 weeks and 1 year after vaccination by counting the reduction in virus-induced plaques in the presence of serial serum dilutions. Adverse events were documented in a 3-week dairy. Viraemia was measured 5 days after vaccination. From 2 weeks up to one year after vaccination, the maximum serum-dilution at which 80% of the virus plaques were neutralized, which indicates protection against Yellow Fever, did not differ between those given a reduced i.d. dose or standard s.c. dose of Vaccine. In all cases the WHO standard of seroprotection (i.e. 80% virus neutralization) was reached (in 77/77 and 78/78, respectively). Similar results were found in the previously vaccinated individuals. Viraemia was detected in half of the primary vaccinated participants, which was not predictive of serological response. In reVaccinees no viraemia was detected.Conclusions:Intradermal administration of one fifth of the amount of Yellow Fever Vaccine administered subcutaneously results in protective seroimmunity in all volunteers. Albeit this vaccination route should enable vaccination of five-times as many individuals at risk for disease, these results should now be confirmed in field studies in areas with potential Yellow Fever virus transmission to change vaccination policy.Trial Registration:Nederlands Trial Register ISRCTN46326316.
Troy D Querec - One of the best experts on this subject based on the ideXlab platform.
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systems biology approach predicts immunogenicity of the Yellow Fever Vaccine in humans
Nature Immunology, 2009Co-Authors: Troy D Querec, Helder I. Nakaya, Rama Akondy, Dirk E Teuwen, Ali Pirani, Kim M Gernert, Jiusheng Deng, Bruz Marzolf, Kathleen A Kennedy, Haiyan WuAbstract:A major challenge for vaccinologists is to understand Vaccine immunogenicity. Pulendran and colleagues use systems biology to determine gene 'signatures' that predict CD8+ T cell and antibody responses to the Yellow Fever Vaccine.
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systems biology approach predicts immunogenicity of the Yellow Fever Vaccine in humans
Nature Immunology, 2009Co-Authors: Troy D Querec, Helder I. Nakaya, Rama Akondy, Dirk E Teuwen, Ali Pirani, Kim M Gernert, Jiusheng Deng, Eva K Lee, Weiping Cao, Bruz MarzolfAbstract:A major challenge in vaccinology is to prospectively determine Vaccine efficacy. Here we have used a systems biology approach to identify early gene 'signatures' that predicted immune responses in humans vaccinated with Yellow Fever Vaccine YF-17D. Vaccination induced genes that regulate virus innate sensing and type I interferon production. Computational analyses identified a gene signature, including complement protein C1qB and eukaryotic translation initiation factor 2 alpha kinase 4-an orchestrator of the integrated stress response-that correlated with and predicted YF-17D CD8(+) T cell responses with up to 90% accuracy in an independent, blinded trial. A distinct signature, including B cell growth factor TNFRS17, predicted the neutralizing antibody response with up to 100% accuracy. These data highlight the utility of systems biology approaches in predicting Vaccine efficacy.
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case of Yellow Fever Vaccine associated viscerotropic disease with prolonged viremia robust adaptive immune responses and polymorphisms in ccr5 and rantes genes
The Journal of Infectious Diseases, 2008Co-Authors: Bali Pulendran, Troy D Querec, Rama Akondy, Joseph I Miller, Nelson B Moseley, Oskar Laur, John Glidewell, Nathan Monson, Sylvija StapransAbstract:Yellow Fever is a mosquitoborne hemorrhagic disease that is endemic in sub-Saharan Africa and tropical South America. The etiologic agent, the Yellow Fever virus (YFV) is a single-stranded RNA virus in the family Flaviviridae, which also includes the dengue and West Nile viruses. After a natural YFV infection, viral replication initially occurs in tissues at the site of infection, but it rapidly spreads to the lymph nodes, blood, and liver [1]. The live attenuated Yellow Fever Vaccine (YF-17D) was developed in the 1930s through experimental attenuation of the Asibi strain of YFV by serial passaging in cell culture [2]. The Vaccine is considered safe and extremely effective, and it has been administered to >500 million people worldwide [3, 4]. Protection is achieved in >98% of recipients, with a duration of at least 10 years and probably much longer, given that significant neutralizing antibody titers may persist for ≥35 years after a single vaccination [3, 4]. Although YF-17D is usually a well-tolerated Vaccine, in rare cases (approximately 1 in 250,000 Vaccinees) individuals develop severe viscerotropic adverse reactions within 2 to 5 days after vaccination; these reactions are sometimes fatal [5–8]. Yellow Fever Vaccine–associated viscerotropic disease is characterized by the failure of multiple organ systems [5–8]. Within 2–5 days after vaccination, patients develop high Fever, malaise, and myalgia, followed by jaundice, oliguria, cardiovascular instability, hemorrhage, and renal and respiratory failure. The case fatality rate is over 50%, and large amounts of YFV antigen may be found in the liver, heart, and other organs, primarily in tissue-associated macrophages [5–9]. The syndrome was first described in 2001, but cases in 1975 and the 1990s were identified retrospectively. To date, a total of 36 cases have been reported worldwide. Genetic mutations in the YFV do not seem to be the cause of the adverse reactions, because in several instances YFV isolated from subjects has had the same consensus nucleotide sequence as the original Vaccine strain virus [8]. Furthermore, the YFV isolates recovered from the subjects showed no reversion to virulence in animal models, suggesting that host factors may be involved in disease [8].
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fatal multiorgan failure due to Yellow Fever Vaccine associated viscerotropic disease
Vaccine, 2007Co-Authors: Jon Belsher, Troy D Querec, Margo A Brinton, Joseph Dellavalla, Robert V Ridenour, Robert S Lanciotti, Andrey A Perelygin, Sherif R Zaki, Christopher D Paddock, Tuofu ZhuAbstract:Yellow Fever Vaccine-associated viscerotropic disease (YEL-AVD) is a rare complication of Yellow Fever (YF) vaccination. A previously healthy 22-year-old female died following YF vaccination despite aggressive measures. Serial viral load titers, cytokine levels and host genetic factors were evaluated in an attempt to understand this unusual and lethal outcome. The patient's high-titer Vaccine viremia and possibly related minor genetic anomalies provide clues to exploring the etiology of YEL-AVD.
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Yellow Fever Vaccine yf 17d activates multiple dendritic cell subsets via tlr2 7 8 and 9 to stimulate polyvalent immunity
Journal of Experimental Medicine, 2006Co-Authors: Troy D Querec, Soumaya Bennouna, Sefik S Alkan, Yasmina Laouar, Keith B Gorden, Richard A Flavell, Shizuo Akira, Rafi Ahmed, Bali PulendranAbstract:The live attenuated Yellow Fever Vaccine 17D (YF-17D) is one of the most effective Vaccines available, with a 65-yr history of use in >400 million people globally. Despite this efficacy, there is presently no information about the immunological mechanisms by which YF-17D acts. Here, we present data that suggest that YF-17D activates multiple Toll-like receptors (TLRs) on dendritic cells (DCs) to elicit a broad spectrum of innate and adaptive immune responses. Specifically, YF-17D activates multiple DC subsets via TLRs 2, 7, 8, and 9 to elicit the proinflammatory cytokines interleukin (IL)-12p40, IL-6, and interferon-α. Interestingly, the resulting adaptive immune responses are characterized by a mixed T helper cell (Th)1/Th2 cytokine profile and antigen-specific CD8+ T cells. Furthermore, distinct TLRs appear to differentially control the Th1/Th2 balance; thus, whilst MyD88-deficient mice show a profound impairment of Th1 cytokines, TLR2-deficient mice show greatly enhanced Th1 and Tc1 responses to YF-17D. Together, these data enhance our understanding of the molecular mechanism of action of YF-17D, and highlight the potential of vaccination strategies that use combinations of different TLR ligands to stimulate polyvalent immune responses.
Marisa A Hong - One of the best experts on this subject based on the ideXlab platform.
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cd4 cd8 ratio and kt ratio predict Yellow Fever Vaccine immunogenicity in hiv infected patients
PLOS Neglected Tropical Diseases, 2016Co-Authors: Vivian Iida Avelinosilva, Peter W Hunt, Yong Huang, Marisol Simoes, Marisa A Hong, Karina Takesaki Miyaji, Sheila Maria Barbosa De Lima, Marcos Da Silva Freire, Helio H CaiaffafilhoAbstract:Author(s): Avelino-Silva, Vivian I; Miyaji, Karina T; Hunt, Peter W; Huang, Yong; Simoes, Marisol; Lima, Sheila B; Freire, Marcos S; Caiaffa-Filho, Helio H; Hong, Marisa A; Costa, Dayane Alves; Dias, Juliana Zanatta C; Cerqueira, Natalia B; Nishiya, Anna Shoko; Sabino, Ester Cerdeira; Sartori, Ana M; Kallas, Esper G | Abstract: BackgroundHIV-infected individuals have deficient responses to Yellow Fever Vaccine (YFV) and may be at higher risk for adverse events (AE). Chronic immune activation-characterized by low CD4/CD8 ratio or high indoleamine 2,3-dioxygenase-1 (IDO) activity-may influence Vaccine response in this population.MethodsWe prospectively assessed AE, viremia by the YFV virus and YF-specific neutralizing antibodies (NAb) in HIV-infected (CD4g350) and -uninfected adults through 1 year after vaccination. The effect of HIV status on initial antibody response to YFV was measured during the first 3 months following vaccination, while the effect on persistence of antibody response was measured one year following vaccination. We explored CD4/CD8 ratio, IDO activity (plasma kynurenine/tryptophan [KT] ratio) and viremia by Human Pegivirus as potential predictors of NAb response to YFV among HIV-infected participants with linear mixed models.Results12 HIV-infected and 45-uninfected participants were included in the final analysis. HIV was not significantly associated with AE, YFV viremia or NAb titers through the first 3 months following vaccination. However, HIV-infected participants had 0.32 times the NAb titers observed for HIV-uninfected participants at 1 year following YFV (95% CI 0.13 to 0.83, p = 0.021), independent of sex, age and prior vaccination. In HIV-infected participants, each 10% increase in CD4/CD8 ratio predicted a mean 21% higher post-baseline YFV Nab titer (p = 0.024). Similarly, each 10% increase in KT ratio predicted a mean 21% lower post-baseline YFV Nab titer (p = 0.009). Viremia by Human Pegivirus was not significantly associated with NAb titers.ConclusionsHIV infection appears to decrease the durability of NAb responses to YFV, an effect that may be predicted by lower CD4/CD8 ratio or higher KT ratio.
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cd4 cd8 ratio predicts Yellow Fever Vaccine induced antibody titers in virologically suppressed hiv infected patients
Journal of Acquired Immune Deficiency Syndromes, 2016Co-Authors: Vivian Iida Avelinosilva, Marisol Simoes, Dayane Alves Costa, Karina Takesaki Miyaji, Augusto Mathias, Juliana Zanatta De Carvalho Dias, Sheila Maria Barbosa De Lima, Marcos Da Silva Freire, Helio H Caiaffafilho, Marisa A HongAbstract:BACKGROUND: Yellow Fever Vaccine (YFV) induces weaker immune responses in HIV-infected individuals. However, little is known about YFV responses among antiretroviral-treated patients and potential immunological predictors of YFV response in this population. METHODS: We enrolled 34 antiretroviral therapy (ART)-treated HIV-infected and 58 HIV-uninfected adults who received a single YFV dose to evaluate antibody levels and predictors of immunity, focusing on CD4(+) T-cell count, CD4(+)/CD8(+) ratio, and Human Pegivirus (GBV-C) viremia. Participants with other immunosuppressive conditions were excluded. RESULTS: Median time since YFV was nonsignificantly shorter in HIV-infected participants than in HIV-uninfected participants (42 and 69 months, respectively, P = 0.16). Mean neutralizing antibody (NAb) titers was lower in HIV-infected participants than HIV-uninfected participants (3.3 vs. 3.6 log10mIU/mL, P = 0.044), a difference that remained significant after adjustment for age, sex, and time since vaccination (P = 0.024). In HIV-infected participants, lower NAb titers were associated with longer time since YFV (rho: -0.38, P = 0.027) and lower CD4(+)/CD8(+) ratio (rho: 0.42, P = 0.014), but not CD4(+) T-cell count (P = 0.52). None of these factors were associated with NAb titers in HIV-uninfected participant. GBV-C viremia was not associated with difference in NAb titers overall or among HIV-infected participants. CONCLUSIONS: ART-treated HIV-infected individuals seem to have impaired and/or less durable responses to YFV than HIV-uninfected individuals, which were associated with lower CD4(+)/CD8(+) ratio, but not with CD4(+) T-cell count. These results supports the notion that low CD4(+)/CD8(+) ratio, a marker linked to persistent immune activation, is a better indicator of functional immune disturbance than CD4(+) T-cell count in patients with successful ART.
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CD4/CD8 Ratio and KT Ratio Predict Yellow Fever Vaccine Immunogenicity in HIV-Infected Patients.
Public Library of Science (PLoS), 2016Co-Authors: Vivian I Avelino-silva, Karina T Miyaji, Peter W Hunt, Yong Huang, Marisol Simoes, Sheila B Lima, Marcos S Freire, Helio H Caiaffa-filho, Marisa A Hong, Dayane Alves CostaAbstract:BACKGROUND:HIV-infected individuals have deficient responses to Yellow Fever Vaccine (YFV) and may be at higher risk for adverse events (AE). Chronic immune activation-characterized by low CD4/CD8 ratio or high indoleamine 2,3-dioxygenase-1 (IDO) activity-may influence Vaccine response in this population. METHODS:We prospectively assessed AE, viremia by the YFV virus and YF-specific neutralizing antibodies (NAb) in HIV-infected (CD4>350) and -uninfected adults through 1 year after vaccination. The effect of HIV status on initial antibody response to YFV was measured during the first 3 months following vaccination, while the effect on persistence of antibody response was measured one year following vaccination. We explored CD4/CD8 ratio, IDO activity (plasma kynurenine/tryptophan [KT] ratio) and viremia by Human Pegivirus as potential predictors of NAb response to YFV among HIV-infected participants with linear mixed models. RESULTS:12 HIV-infected and 45-uninfected participants were included in the final analysis. HIV was not significantly associated with AE, YFV viremia or NAb titers through the first 3 months following vaccination. However, HIV-infected participants had 0.32 times the NAb titers observed for HIV-uninfected participants at 1 year following YFV (95% CI 0.13 to 0.83, p = 0.021), independent of sex, age and prior vaccination. In HIV-infected participants, each 10% increase in CD4/CD8 ratio predicted a mean 21% higher post-baseline YFV Nab titer (p = 0.024). Similarly, each 10% increase in KT ratio predicted a mean 21% lower post-baseline YFV Nab titer (p = 0.009). Viremia by Human Pegivirus was not significantly associated with NAb titers. CONCLUSIONS:HIV infection appears to decrease the durability of NAb responses to YFV, an effect that may be predicted by lower CD4/CD8 ratio or higher KT ratio
Sheila Maria Barbosa De Lima - One of the best experts on this subject based on the ideXlab platform.
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duration of post vaccination immunity to Yellow Fever in volunteers eight years after a dose response study
Vaccine, 2018Co-Authors: Reinaldo De Menezes Martins, Sheila Maria Barbosa De Lima, Maria De Lourdes De Sousa Maia, Tatiana Guimaraes De Noronha, Janaina Reis Xavier, Luiz Antonio Bastos Camacho, Elizabeth Maciel De Albuquerque, Roberto Henrique Guedes Farias, Thalita Da Matta De Castro, A K O HommaAbstract:Abstract In 2009, Bio-Manguinhos conducted a dose-response study with the Yellow Fever Vaccine, administering the Vaccine in the usual mean dose of 27,476 IU (full dose, reference) and in tapered doses (10,447 IU, 3013 IU, 587 IU, 158 IU, and 31 IU) by the usual subcutaneous route and usual volume (0.5 mL). Tapered doses were obtained by dilution in the manufacturer’s laboratory, and the test batches presented industrial quality. Doses down to 587 IU showed similar immunogenicity to the full dose (27,476, reference), while the 158 IU and 31 IU doses displayed lower immunogenicity. Seropositivity was maintained at 10 months, except in the group that received the 31 IU dose. The current study aims to determine whether Yellow Fever seropositivity was maintained eight years after YF vaccination in non-revaccinated individuals. According to the current study’s results, seropositivity was maintained in 85% of 318 participants and was similar across groups. The findings support the use of the Yellow Fever Vaccine in fractional doses during outbreaks, but each fractional dose should have at least 587 IU. This study also supports the minimum dose required by WHO, 1000 IU. Clinical trials registration: Clinicaltrials.gov NCT 03338231 .
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cd4 cd8 ratio and kt ratio predict Yellow Fever Vaccine immunogenicity in hiv infected patients
PLOS Neglected Tropical Diseases, 2016Co-Authors: Vivian Iida Avelinosilva, Peter W Hunt, Yong Huang, Marisol Simoes, Marisa A Hong, Karina Takesaki Miyaji, Sheila Maria Barbosa De Lima, Marcos Da Silva Freire, Helio H CaiaffafilhoAbstract:Author(s): Avelino-Silva, Vivian I; Miyaji, Karina T; Hunt, Peter W; Huang, Yong; Simoes, Marisol; Lima, Sheila B; Freire, Marcos S; Caiaffa-Filho, Helio H; Hong, Marisa A; Costa, Dayane Alves; Dias, Juliana Zanatta C; Cerqueira, Natalia B; Nishiya, Anna Shoko; Sabino, Ester Cerdeira; Sartori, Ana M; Kallas, Esper G | Abstract: BackgroundHIV-infected individuals have deficient responses to Yellow Fever Vaccine (YFV) and may be at higher risk for adverse events (AE). Chronic immune activation-characterized by low CD4/CD8 ratio or high indoleamine 2,3-dioxygenase-1 (IDO) activity-may influence Vaccine response in this population.MethodsWe prospectively assessed AE, viremia by the YFV virus and YF-specific neutralizing antibodies (NAb) in HIV-infected (CD4g350) and -uninfected adults through 1 year after vaccination. The effect of HIV status on initial antibody response to YFV was measured during the first 3 months following vaccination, while the effect on persistence of antibody response was measured one year following vaccination. We explored CD4/CD8 ratio, IDO activity (plasma kynurenine/tryptophan [KT] ratio) and viremia by Human Pegivirus as potential predictors of NAb response to YFV among HIV-infected participants with linear mixed models.Results12 HIV-infected and 45-uninfected participants were included in the final analysis. HIV was not significantly associated with AE, YFV viremia or NAb titers through the first 3 months following vaccination. However, HIV-infected participants had 0.32 times the NAb titers observed for HIV-uninfected participants at 1 year following YFV (95% CI 0.13 to 0.83, p = 0.021), independent of sex, age and prior vaccination. In HIV-infected participants, each 10% increase in CD4/CD8 ratio predicted a mean 21% higher post-baseline YFV Nab titer (p = 0.024). Similarly, each 10% increase in KT ratio predicted a mean 21% lower post-baseline YFV Nab titer (p = 0.009). Viremia by Human Pegivirus was not significantly associated with NAb titers.ConclusionsHIV infection appears to decrease the durability of NAb responses to YFV, an effect that may be predicted by lower CD4/CD8 ratio or higher KT ratio.
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cd4 cd8 ratio predicts Yellow Fever Vaccine induced antibody titers in virologically suppressed hiv infected patients
Journal of Acquired Immune Deficiency Syndromes, 2016Co-Authors: Vivian Iida Avelinosilva, Marisol Simoes, Dayane Alves Costa, Karina Takesaki Miyaji, Augusto Mathias, Juliana Zanatta De Carvalho Dias, Sheila Maria Barbosa De Lima, Marcos Da Silva Freire, Helio H Caiaffafilho, Marisa A HongAbstract:BACKGROUND: Yellow Fever Vaccine (YFV) induces weaker immune responses in HIV-infected individuals. However, little is known about YFV responses among antiretroviral-treated patients and potential immunological predictors of YFV response in this population. METHODS: We enrolled 34 antiretroviral therapy (ART)-treated HIV-infected and 58 HIV-uninfected adults who received a single YFV dose to evaluate antibody levels and predictors of immunity, focusing on CD4(+) T-cell count, CD4(+)/CD8(+) ratio, and Human Pegivirus (GBV-C) viremia. Participants with other immunosuppressive conditions were excluded. RESULTS: Median time since YFV was nonsignificantly shorter in HIV-infected participants than in HIV-uninfected participants (42 and 69 months, respectively, P = 0.16). Mean neutralizing antibody (NAb) titers was lower in HIV-infected participants than HIV-uninfected participants (3.3 vs. 3.6 log10mIU/mL, P = 0.044), a difference that remained significant after adjustment for age, sex, and time since vaccination (P = 0.024). In HIV-infected participants, lower NAb titers were associated with longer time since YFV (rho: -0.38, P = 0.027) and lower CD4(+)/CD8(+) ratio (rho: 0.42, P = 0.014), but not CD4(+) T-cell count (P = 0.52). None of these factors were associated with NAb titers in HIV-uninfected participant. GBV-C viremia was not associated with difference in NAb titers overall or among HIV-infected participants. CONCLUSIONS: ART-treated HIV-infected individuals seem to have impaired and/or less durable responses to YFV than HIV-uninfected individuals, which were associated with lower CD4(+)/CD8(+) ratio, but not with CD4(+) T-cell count. These results supports the notion that low CD4(+)/CD8(+) ratio, a marker linked to persistent immune activation, is a better indicator of functional immune disturbance than CD4(+) T-cell count in patients with successful ART.
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17dd Yellow Fever Vaccine a double blind randomized clinical trial of immunogenicity and safety on a dose response study
Human Vaccines & Immunotherapeutics, 2013Co-Authors: Reinaldo De Menezes Martins, Sheila Maria Barbosa De Lima, Marcos Da Silva Freire, Maria De Lourdes De Sousa Maia, Luiz Antonio Bastos Camacho, Roberto Henrique Guedes Farias, Anna M Y Yamamura, Ricardo Galler, L F C Almeida, Rita Maria Ribeiro NogueiraAbstract:Objective: To verify if the Bio-Manguinhos 17DD Yellow Fever Vaccine (17DD-YFV) used in lower doses is as immunogenic and safe as the current formulation.Results: Doses from 27,476 IU to 587 IU ind...
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17dd Yellow Fever Vaccine a double blind randomized clinical trial of immunogenicity and safety on a dose response study
Human Vaccines & Immunotherapeutics, 2013Co-Authors: Reinaldo De Menezes Martins, Sheila Maria Barbosa De Lima, Marcos Da Silva Freire, Maria De Lourdes De Sousa Maia, Luiz Antonio Bastos Camacho, Roberto Henrique Guedes Farias, Anna M Y Yamamura, Ricardo Galler, L F C Almeida, Rita Maria Ribeiro NogueiraAbstract:Objective: To verify if the Bio-Manguinhos 17DD Yellow Fever Vaccine (17DD-YFV) used in lower doses is as immunogenic and safe as the current formulation. Results: Doses from 27,476 IU to 587 IU induced similar seroconversion rates and neutralizing antibodies geometric mean titers (GMTs). Immunity of those who seroconverted to YF was maintained for 10 mo. Reactogenicity was low for all groups. Methods: Young and healthy adult males (n = 900) were recruited and randomized into 6 groups, to receive deescalating doses of 17DD-YFV, from 27,476 IU to 31 IU. Blood samples were collected before vaccination (for neutralization tests to Yellow Fever, serology for dengue and clinical chemistry), 3 to 7 d after vaccination (for viremia and clinical chemistry) and 30 d after vaccination (for new Yellow Fever serology and clinical chemistry). Adverse events diaries were filled out by volunteers during 10 d after vaccination. Volunteers were retested for Yellow Fever and dengue antibodies 10 mo later. Seropositivity for dengue was found in 87.6% of volunteers before vaccination, but this had no significant influence on conclusions. Conclusion: In young healthy adults Bio-Manguinhos/Fiocruz Yellow Fever Vaccine can be used in much lower doses than usual.