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

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 (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.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.

Role of human Pegivirus infections in whole Plasmodium falciparum sporozoite vaccination and controlled human malaria infection in African volunteers

“…Here, we observed lower, albeit not statistically significant, median anti-PfCSP titres in the HPgV-1 positive versus the negative group at baseline and 14 days past last vaccination. These observations mirror findings by Avelino-Silva et al, who showed no association between HPgV-1 infection status/viremia with yellow fever specific neutralizing antibody titres in HIV-1 positive individuals immunized with yellow fever vaccine [ 82 ]. While studies have extensively tried to understand potential inhibition mechanisms induced by HPgV-1 (and other Flaviviruses) on T cell activation [ 77 , 83 ], activation pathways that might be affected in B cells are less explored.…”

Role of Human Pegivirus Infections in Whole P. falciparum Sporozoite Vaccination and Controlled Human Malaria Infection in African Volunteers

“…Here, we observed lower, albeit not statistically significant, median anti-CSP titres in the HPgV-1 positive versus the HPgV-1 negative group at baseline and 14 days past last vaccination. These observations mirror findings by Avelino-Silva et al, who found no association between HPgV infection status/viremia with yellow fever specific neutralizing antibody titers in HIV-1 positive individuals immunized with yellow fever vaccine [83]. While studies have extensively tried to understand potential inhibition mechanisms induced by HPgV-1 (and other Flaviviruses) on T cell activation [78,84] activation pathways that might be affected in B cells are less explored.…”

Lipidomic analysis of immune activation in equine leptospirosis and Leptospira-vaccinated horses

“…There is an ever increasing knowledge base regarding the biochemistry of the immune response during infections and inflammatory diseases. A shift in the Th1 and Th2 responses generally results in up-regulation of Th2-type pro-inflammatory cytokines with bacterial infections [ 26 , 27 ], viral infections [ 28 , 29 ], and parasitic invasions [ 30 ]. In addition local immune responses, such as in the lung [ 31 ], brain [ 32 ], and the intestine in inflammatory bowel disease (Crohn's Disease and Ulcerative Colitis) [ 33 ] elicit alterations in the Th1 and Th2 cytokine responses.…”