title: Strong viremia control in vaccinated macaques does not prevent gradual Th17 cell loss from central memory.
abstract: It has been proposed that microbial translocation might play a role in chronic immune activation during HIV/SIV infection. Key roles in fighting bacterial and fungal infections have been attributed to Th17 and Tc17 cells. Th17 cells can be infected with HIV/SIV, however whether effective vaccination leads to their maintenance following viral challenge has not been addressed. Here we retrospectively investigated if a vaccine regimen that potently reduced viremia post-challenge preserved Th17 and Tc17 cells, thus adding benefit in the absence of sterilizing protection. Rhesus macaques were previously vaccinated with replication-competent Adenovirus recombinants expressing HIVtat and HIVenv followed by Tat and gp140 protein boosting. Upon SHIV(89.6P) challenge, the vaccines exhibited a significant 4 log reduction in chronic viremia compared to sham vaccinated controls which rapidly progressed to AIDS [39]. Plasma and cryopreserved PBMC samples were examined pre-challenge and during acute and chronic infection. Control macaques exhibited a rapid loss of CD4(+) cells, including Th17 cells. Tc17 cells tended to decline over the course of infection although significance was not reached. Immune activation, assessed by Ki-67 expression, was associated with elevated chronic viremia of the controls. Significantly increased plasma IFN-γ levels were also observed. No increase in plasma LPS levels were observed suggesting a lack of microbial translocation. In contrast, vaccinated macaques had no evidence of immune activation within the chronic phase and preserved both CD4(+) T-cells and Tc17 cells in PBMC. Nevertheless, they exhibited a gradual, significant loss of Th17 cells which concomitantly displayed significantly higher CCR6 expression over time. The gradual Th17 cell decline may reflect mucosal homing to inflammatory sites and/or slow depletion due to ongoing low levels of SHIV replication. Our results suggest that potent viremia reduction during chronic SHIV infection will delay but not prevent the loss of Th17 cells.
authors.affiliation: National Cancer Institute, Vaccine Branch, Bethesda, MD 20892, USA.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Demberg
authors.forename: Amelia C
authors.initials: AC
authors.lastname: Ettinger
authors.forename: Stanley
authors.initials: S
authors.lastname: Aladi
authors.forename: Katherine
authors.initials: K
authors.lastname: McKinnon
authors.forename: Thea
authors.initials: T
authors.lastname: Kuddo
authors.forename: David
authors.initials: D
authors.lastname: Venzon
authors.forename: L Jean
authors.initials: LJ
authors.lastname: Patterson
authors.forename: Terry M
authors.initials: TM
authors.lastname: Phillips
authors.forename: Marjorie
authors.initials: M
authors.lastname: Robert-Guroff
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000276:immunology; D000818:Animals; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity; D007156:Immunologic Memory / Q000276:immunology*; D008253:Macaca mulatta; D018449:SAIDS Vaccines / Q000008:administration & dosage* / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology / Q000472:pathogenicity; D058504:Th17 Cells / Q000276:immunology*; D014611:Vaccination; D014766:Viremia / Q000276:immunology / Q000517:prevention & control* / Q000821:virology
chemical_list: D016915:AIDS Vaccines; D018449:SAIDS Vaccines