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

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


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.

MeSH terms

  • Adult
  • Antibodies, Neutralizing / blood
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / blood
  • CD4-CD8 Ratio*
  • Female
  • HIV Infections / immunology*
  • HIV Infections / virology
  • Humans
  • Immunogenicity, Vaccine*
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
  • Kynurenine / blood*
  • Male
  • Middle Aged
  • Prospective Studies
  • Tryptophan / blood*
  • Viremia
  • Yellow Fever / immunology
  • Yellow Fever / prevention & control*
  • Yellow Fever / virology
  • Yellow Fever Vaccine / adverse effects
  • Yellow Fever Vaccine / immunology*
  • Yellow fever virus / immunology


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • IDO1 protein, human
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Yellow Fever Vaccine
  • Kynurenine
  • Tryptophan