Dataset Information

CD4/CD8 Ratio and KT Ratio Predict Yellow Fever Vaccine Immunogenicity in HIV-Infected Patients.

ABSTRACT:

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.

SUBMITTER: Avelino-Silva VI

PROVIDER: S-EPMC5179051 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Publications

CD4/CD8 Ratio and KT Ratio Predict Yellow Fever Vaccine Immunogenicity in HIV-Infected Patients.

Avelino-Silva Vivian I VI Miyaji Karina T KT Hunt Peter W PW Huang Yong Y Simoes Marisol M Lima Sheila B SB Freire Marcos S MS Caiaffa-Filho Helio H HH Hong Marisa A MA Costa Dayane Alves DA Dias Juliana Zanatta C JZ Cerqueira Natalia B NB Nishiya Anna Shoko AS Sabino Ester Cerdeira EC Sartori Ana M AM Kallas Esper G EG

PLoS neglected tropical diseases 20161212 12

<h4>Background</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 27941965

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Project description:BACKGROUND:In 2016, the response to a yellow fever outbreak in Angola and the Democratic Republic of Congo led to a global shortage of yellow fever vaccine. As a result, a fractional dose of the 17DD yellow fever vaccine (containing one fifth [0.1 ml] of the standard dose) was offered to 7.6 million children 2 years of age or older and nonpregnant adults in a preemptive campaign in Kinshasa. The goal of this study was to assess the immune response to the fractional dose in a large-scale campaign. METHODS:We recruited participants in four age strata at six vaccination sites. We assessed neutralizing antibody titers against yellow fever virus in blood samples obtained before vaccination and at 1 month and 1 year after vaccination, using a plaque reduction neutralization test with a 50% cutoff (PRNT50). Participants with a PRNT50 titer of 10 or higher were considered to be seropositive. Those with a baseline titer of less than 10 who became seropositive at follow-up were classified as having undergone seroconversion. Participants who were seropositive at baseline and who had an increase in the titer by a factor of 4 or more at follow-up were classified as having an immune response. RESULTS:Among 716 participants who completed the 1-month follow-up, 705 (98%; 95% confidence interval [CI], 97 to 99) were seropositive after vaccination. Among 493 participants who were seronegative at baseline, 482 (98%; 95% CI, 96 to 99) underwent seroconversion. Among 223 participants who were seropositive at baseline, 148 (66%; 95% CI, 60 to 72) had an immune response. Lower baseline titers were associated with a higher probability of having an immune response (P<0.001). Among 684 participants who completed the 1-year follow-up, 666 (97%; 95% CI, 96 to 98) were seropositive for yellow fever antibody. The distribution of titers among the participants who were seronegative for yellow fever antibody at baseline varied significantly among age groups at 1 month and at 1 year (P<0.001 for both comparisons). CONCLUSIONS:A fractional dose of the 17DD yellow fever vaccine was effective at inducing seroconversion in participants who were seronegative at baseline. Titers remained above the threshold for seropositivity at 1 year after vaccination in nearly all participants who were seropositive at 1 month after vaccination. These findings support the use of fractional-dose vaccination for outbreak control. (Funded by the U.S. Agency for International Development and the Centers for Disease Control and Prevention.).

Project description:We previously reported construction of a chimeric yellow fever-dengue type 2 virus (YF/DEN2) and determined its safety and protective efficacy in rhesus monkeys (F. Guirakhoo et al., J. Virol. 74:5477-5485, 2000). In this paper, we describe construction of three additional YF/DEN chimeras using premembrane (prM) and envelope (E) genes of wild-type (WT) clinical isolates: DEN1 (strain PUO359, isolated in 1980 in Thailand), DEN3 (strain PaH881/88, isolated in 1988 in Thailand), and DEN4 (strain 1228, isolated in 1978 in Indonesia). These chimeric viruses (YF/DEN1, YF/DEN3, and YF/DEN4) replicated to ~7.5 log(10) PFU/ml in Vero cells, were not neurovirulent in 3- to 4-week-old ICR mice inoculated by the intracerebral route, and were immunogenic in monkeys. All rhesus monkeys inoculated subcutaneously with one dose of these chimeric viruses (as monovalent or tetravalent formulation) developed viremia with magnitudes similar to that of the YF 17D vaccine strain (YF-VAX) but significantly lower than those of their parent WT viruses. Eight of nine monkeys inoculated with monovalent YF/DEN1 -3, or -4 vaccine and six of six monkeys inoculated with tetravalent YF/DEN1-4 vaccine seroconverted after a single dose. When monkeys were boosted with a tetravalent YF/DEN1-4 dose 6 months later, four of nine monkeys in the monovalent YF/DEN groups developed low levels of viremia, whereas no viremia was detected in any animals previously inoculated with either YF/DEN1-4 vaccine or WT DEN virus. An anamnestic response was observed in all monkeys after the second dose. No statistically significant difference in levels of neutralizing antibodies was observed between YF virus-immune and nonimmune monkeys which received the tetravalent YF/DEN1-4 vaccine or between tetravalent YF/DEN1-4-immune and nonimmune monkeys which received the YF-VAX. However, preimmune monkeys developed either no detectable viremia or a level of viremia lower than that in nonimmune controls. This is the first recombinant tetravalent dengue vaccine successfully evaluated in nonhuman primates.

Dataset Information

CD4/CD8 Ratio and KT Ratio Predict Yellow Fever Vaccine Immunogenicity in HIV-Infected Patients.

Background

Methods

Results

Conclusions

Publications

CD4/CD8 Ratio and KT Ratio Predict Yellow Fever Vaccine Immunogenicity in HIV-Infected Patients.

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