Plasmodium inui infection reduces the efficacy of a simian immunodeficiency virus DNA vaccine in a rhesus macaque model through alteration of the vaccine-induced immune response.
Human immunodeficiency virus type 1 and malaria are co-endemic in many areas. We evaluated the effects of Plasmodium inui infection on the performance of a simian immunodeficiency virus (SIV) DNA vaccine. Rhesus macaques were infected with P. inui by transfusion of whole blood from a persistently infected animal. Animals with and animals without P. inui infection were then vaccinated 4 times with an SIV DNA vaccine encoding SIVgag, SIVpol, and SIVenv. Animals were subsequently challenged with thirty 50% rhesus monkey infectious doses of SIVmac251 6 weeks after the last vaccination. P. inui-infected immunized animals showed a significantly higher viral load than animals without P. inui infection (P = .010, by the Wilcoxon rank sum test). The higher viral loads in the P. inui-infected animals were durable and were observed at all sampling time points across the study (P = .00245, by the Wilcoxon rank test). The P. inui-infected animals also had correspondingly lower CD4(+) cell counts. There were fewer vaccine-specific CD4(+) and CD8(+) cells in the P. inui-infected animals, compared with uninfected animals. Of importance, P. inui infection seemed to decrease the number of CD8(+) cells that could proliferate or secrete interferon γ, although the number of CD8(+) cells capable of secreting tumor necrosis factor α following in vitro stimulation was increased. This study demonstrated that P. inui infection had an influence on the immune response to an SIV DNA vaccine and decreased the vaccine's efficacy.
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Jiangmei
J
Yin
Maryanne T
MT
Vahey
Anlan
A
Dai
Mark G
MG
Lewis
Tatiana
T
Arango
Jake
J
Yalley-Ogunro
Jack
J
Greenhouse
Karla
K
Mendoza
Amir
A
Khan
Niranjan Y
NY
Sardesai
Walter
W
Weiss
Jack
J
Komisar
Jean D
JD
Boyer
D000818:Animals; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D007371:Interferon-gamma / Q000378:metabolism; D008253:Macaca mulatta; D008288:Malaria / Q000276:immunology*; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology* / Q000302:isolation & purification; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014611:Vaccination / Q000379:methods; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D019562:Viral Load; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology
D018449:SAIDS Vaccines; D014409:Tumor Necrosis Factor-alpha; D019444:Vaccines, DNA; D014764:Viral Proteins; D007371:Interferon-gamma