Correction: Transduction of SIV-Specific TCR Genes into Rhesus Macaque CD8+ T Cells Conveys the Ability to Suppress SIV Replication.

[This corrects the article DOI: 10.1371/journal.pone.

Enhanced early innate and T cell-mediated responses in subjects immunized with Anthrax Vaccine Adsorbed Plus CPG 7909 (AV7909).

NuThrax™ (Anthrax Vaccine Adsorbed with CPG 7909 Adjuvant) (AV7909) is in development. Samples obtained in a phase Ib clinical trial were tested to confirm biomarkers of innate immunity and evaluate effects of CPG 7909 (PF-03512676) on adaptive immunity. Subjects received two intramuscular doses of commercial BioThrax(®) (Anthrax Vaccine Adsorbed, AVA), or two intramuscular doses of one of four formulations of AV7909.

Transduction of SIV-specific TCR genes into rhesus macaque CD8+ T cells conveys the ability to suppress SIV replication.

Background: The SIV/rhesus macaque model for HIV/AIDS is a powerful system for examining the contribution of T cells in the control of AIDS viruses. To better our understanding of CD8(+) T-cell control of SIV replication in CD4(+) T cells, we asked whether TCRs isolated from rhesus macaque CD8(+) T-cell clones that exhibited varying abilities to suppress SIV replication could convey their suppressive properties to CD8(+) T cells obtained from an uninfected/unvaccinated animal.

Principal Findings: We transferred SIV-specific TCR genes isolated from rhesus macaque CD8(+) T-cell clones with varying abilities to suppress SIV replication in vitro into CD8(+) T cells obtained from an uninfected animal by retroviral transduction.

TCR triggering transcriptionally downregulates CCR5 expression on rhesus macaque CD4(+) T-cells with no measurable effect on susceptibility to SIV infection.

Studies using transformed human cell lines suggest that most SIV strains use CCR5 as co-receptor. Our analysis of primary rhesus macaque CD4(+) T-cell clones revealed marked differences in susceptibility to SIV(mac)239 infection. We investigated whether different levels of CCR5 expression account for clonal differences in SIV(mac)239 susceptibility.

Long-lasting humoral and cellular immune responses and mucosal dissemination after intramuscular DNA immunization.

Naïve Indian rhesus macaques were immunized with a mixture of optimized plasmid DNAs expressing several SIV antigens using in vivo electroporation via the intramuscular route. The animals were monitored for the development of SIV-specific systemic (blood) and mucosal (bronchoalveolar lavage) cellular and humoral immune responses. The immune responses were of great magnitude, broad (Gag, Pol, Nef, Tat and Vif), long-lasting (up to 90 weeks post third vaccination) and were boosted with each subsequent immunization, even after an extended 90-week rest period.

Distribution, persistence, and efficacy of adoptively transferred central and effector memory-derived autologous simian immunodeficiency virus-specific CD8+ T cell clones in rhesus macaques during acute infection.

Plasma viremia decreases coincident with the appearance of virus-specific CD8(+) T cells during acute HIV or SIV infection. This finding, along with demonstrations of viral mutational escape from CD8(+) T cell responses and transient increase in plasma viremia after depletion of CD8(+) T cells in SIV-infected monkeys strongly suggest a role for CD8(+) T cells in controlling HIV/SIV. However, direct quantitative or qualitative correlates between CD8(+) T cell activity and virus control have not been established.

Trafficking, persistence, and activation state of adoptively transferred allogeneic and autologous Simian Immunodeficiency Virus-specific CD8(+) T cell clones during acute and chronic infection of rhesus macaques.

Despite multiple lines of evidence suggesting their involvement, the precise role of CD8(+) T cells in controlling HIV replication remains unclear. To determine whether CD8(+) T cells can limit retroviral replication in the absence of other immune responses, we transferred 1-13 x 10(9) allogeneic in vitro expanded SIV-specific CD8(+) T cell clones matched for the relevant restricting MHC-I allele into rhesus macaques near the time of i.v.

Nef-mediated MHC class I down-regulation unmasks clonal differences in virus suppression by SIV-specific CD8(+) T cells independent of IFN-gamma and CD107a responses.

CD8(+) T lymphocytes (CTL) play a role in controlling HIV/SIV infection. CTL antiviral activity is dependent on recognition of antigenic peptides associated with MHC class I molecules on infected target cells, and CTL activation can be impaired by Nef-mediated down-regulation of MHC class I molecules. We tested the ability of a series of rhesus macaque CD8(+) T-cell clones specific for the SIV Gag CM9 peptide to suppress SIV infection of autologous CD4(+) T cells.

ELISpot displays a better detection over ELISA of T helper (Th) 2-type cytokine-production by ex vivo-stimulated antigen-specific T cells from human peripheral blood.

Detection of cytokines secreted by ex vivo antigen-stimulated peripheral blood mononuclear cells (PBMC) by ELISA is hampered by low frequencies of specific T cells and cellular receptor consumption. We investigated if ELISpot, measuring cytokine production at the single cell level, facilitated a better detection of the Th2 cytokines IL-4 and IL-5. PBMC from nickel-allergic (n = 31) and non-allergic subjects (n = 10) were stimulated with nickel or tetanus toxoid (TT) and cytokine production assessed by ELISpot and ELISA.

The Mamu B 17-restricted SIV Nef IW9 to TW9 mutation abrogates correct epitope processing and presentation without loss of replicative fitness.

CD8(+) cytotoxic T lymphocytes (CTL) play an important role in controlling virus replication in HIV- and SIV-infected humans and monkeys, respectively. Three well-studied SIV CTL determinants are the two Mamu A()01-restricted epitopes Gag CM9 and Tat SL8, and the Mamu B()17-restricted epitope Nef IW9. Point mutations leading to amino acid replacements in these epitopes have been reported to mediate SIV escape from CTL control.

Efficient inhibition of SIV replication in rhesus CD4+ T-cell clones by autologous immortalized SIV-specific CD8+ T-cell clones.

CD8(+) cytotoxic T lymphocyte (CTL) responses play an important role in controlling the replication of primate lentiviruses. Induction of these responses is a key objective for most current AIDS vaccine approaches. Despite a variety of approaches for measuring properties and activities of CTL, the functions responsible for controlling viral replication in vivo have not been clearly identified.

Pregnancy, but not the allergic status, influences spontaneous and induced interleukin-1beta (IL-1beta), IL-6, IL-10 and IL-12 responses.

In this study, we investigated how pregnancy influences cytokine production in response to stimulation of the innate and the adaptive immune system, respectively. Peripheral blood mononuclear cells (PBMCs) from allergic (n = 44) and non-allergic (n = 36) women were collected at three time-points: during the third trimester, at delivery and at a non-pregnant state 2 years after delivery. The production of interleukin-1beta (IL-1beta), IL-6, IL-10 and IL-12 was measured by enzyme-linked immunosorbent assay (ELISA) or enzyme-linked immunospot assay (ELISPOT).

The effect of maternal, umbilical cord and placental malaria parasitaemia on the birthweight of newborns from South-western Cameroon.

Aim: The impact of maternal, umbilical cord and placental malaria parasitaemia on the incidence of low birthweight was investigated in pregnant women reporting for delivery at the Mutengene Maternity Centre, Fako Division, South West Province, Cameroon.

Methods: The malaria parasitaemia status of 770 umbilical cords, parturient women and placental impression smears were determined by light microscopy using blood samples collected between June 1999 and September 2001. The birthweights (BW) of the newborns were recorded soon after delivery.

Plasmodium falciparum inhibitory capacities of paired maternal-cord sera from south-west province, Cameroon.

In malaria endemic areas, young children are protected against malaria attack during the first few weeks of life partially by transplacentally acquired antibodies. In this study, we show, using an in vitro assay, that part of these antibodies are involved with blocking the re-invasion of host red blood cells by erythrocytic merozoites. One hundred consecutive paired maternal-cord blood samples were collected at delivery and their plasma assayed for total IgG antibodies against crude blood stage antigens by the ELISA.

Studies on Plasmodium falciparum isotypic antibodies and numbers of IL-4 and IFN-gamma secreting cells in paired maternal cord blood from South West Cameroon.

Objectives: In this study, the effect of maternal peripheral and placental Plasmodium falciparum parasitaemia on the level of antibody and cytokine immune responses in the neonate was investigated.

Methods: Malaria parasites were detected by light microscopy. Levels of malaria-specific isotypic antibodies were measured in maternal and cord blood by indirect ELISA.

Haptoglobin phenotypes and malaria infection in pregnant women at delivery in western Cameroon.

Plasmodium falciparum-infected erythrocytes have been reported to sequester in the placenta by adhering to chondroitin 4-sulfate during pregnancy. Earlier studies have highlighted higher susceptibility of primigravidae to P. falciparum compared to multigravidae living within the same endemic areas.