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.

Abstract

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.

• Authors: Jiangmei Yin, Maryanne T Vahey, Anlan Dai, Mark G Lewis, Tatiana Arango, Jake Yalley-Ogunro, Jack Greenhouse, Karla Mendoza, Amir Khan, Niranjan Y Sardesai, Walter Weiss, Jack Komisar, Jean D Boyer
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 206 Issue 4 Pg. 523-33 (Aug 15 2012) ISSN: 1537-6613 [Electronic] United States
• PMID: 22693228 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• SAIDS Vaccines
• Tumor Necrosis Factor-alpha
• Vaccines, DNA
• Viral Proteins
• Interferon-gamma

Topics

• Animals
• CD4 Lymphocyte Count
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Cell Proliferation
• Interferon-gamma (metabolism)
• Macaca mulatta
• Malaria (immunology)
• SAIDS Vaccines (administration & dosage, immunology)
• Simian Immunodeficiency Virus (immunology, isolation & purification)
• Tumor Necrosis Factor-alpha (metabolism)
• Vaccination (methods)
• Vaccines, DNA (administration & dosage, immunology)
• Viral Load
• Viral Proteins (genetics, immunology)