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

• Published in: The Journal of infectious diseases 2012-08, Vol.206 (4), p.523-533
• Main Authors: Yin, Jiangmei, Vahey, Maryanne T., Dai, Anlan, Lewis, Mark G., Arango, Tatiana, Yalley-Ogunro, Jake, Greenhouse, Jack, Mendoza, Karla, Khan, Amir, Sardesai, Niranjan Y., Weiss, Walter, Komisar, Jack, Boyer, Jean D.
• Format: Article
• Language: English
• Subjects: Animals; Antigens; Biological and medical sciences; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Cell Proliferation; Cytokines; DNA vaccines; Fundamental and applied biological sciences. Psychology; HIV 1; HIV/AIDS; Human immunodeficiency virus 1; Immunization; Infections; Infectious diseases; Interferon-gamma - secretion; Macaca mulatta; Major and Brief Reports; Malaria; Malaria - immunology; Medical sciences; Microbiology; Miscellaneous; Plasmodium inui; SAIDS Vaccines - administration & dosage; SAIDS Vaccines - immunology; Simian immunodeficiency virus; Simian Immunodeficiency Virus - immunology; Simian Immunodeficiency Virus - isolation & purification; Swine influenza virus; T lymphocytes; Tumor Necrosis Factor-alpha - secretion; Vaccination; Vaccination - methods; Vaccines, DNA - administration & dosage; Vaccines, DNA - immunology; Viral Load; Viral Proteins - genetics; Viral Proteins - immunology; Virology
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jis404

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.