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. 2016 Dec 12;10(12):e0005219.
doi: 10.1371/journal.pntd.0005219. eCollection 2016 Dec.

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

Vivian I Avelino-Silva  1   2 , Karina T Miyaji  1 , Peter W Hunt  2 , Yong Huang  3 , Marisol Simoes  4 , Sheila B Lima  4 , Marcos S Freire  4 , Helio H Caiaffa-Filho  5   6 , Marisa A Hong  5   7 , Dayane Alves Costa  7 , Juliana Zanatta C Dias  7 , Natalia B Cerqueira  7 , Anna Shoko Nishiya  8 , Ester Cerdeira Sabino  1   8 , Ana M Sartori  1 , Esper G Kallas  1   7
Affiliations

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

Vivian I Avelino-Silva et al. PLoS Negl Trop Dis. .

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.

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Conflict of interest statement

MSF, MS and SBL are employees at Bio-manguinhos-FIOCRUZ, the main national manufacturer of yellow fever vaccine in Brazil. All remaining authors declare no competing interests.

Figures

Fig 1
Fig 1. Overview of study procedures.
YFV, Yellow Fever vaccine; NAb, neutralizing antibodies; KT, kynurenine/tryptophan; CBC, complete blood count; HIV, human immunodeficiency virus; AE, adverse events
Fig 2
Fig 2
CD4+ T cell counts for HIV-infected participants (N = 12) across study visits (Panel A) and HIV VL across visits for participants with VL above the limit of detection at baseline (N = 4, Panel B). Individual subjects are represented by distinct lines in the graph.
See this image and copyright information in PMC

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