- Primary Human Neutrophils Exhibit a Unique HIV-Directed Antibody-Dependent Phagocytosis Profile. [Journal Article]
- JIJ Innate Immun 2018 Dec 17; :1-10
- The only clinical HIV vaccine trial to demonstrate efficacy, RV144, correlated protection with the antibodies (Abs) mediating function via the "constant" immunoglobulin region, the crystallizable fra...
The only clinical HIV vaccine trial to demonstrate efficacy, RV144, correlated protection with the antibodies (Abs) mediating function via the "constant" immunoglobulin region, the crystallizable fragment (Fc). These data have supported a focus on the induction of Abs by vaccines that trigger antiviral activities by relevant leukocytes via Fc receptors (FcRs). Neutrophils are phagocytes that comprise > 50% of leukocytes and display unique FcRs. We sought to compare the Ab-dependent cellular phagocytosis (ADCP) activity of human neutrophils to the commonly assayed THP-1 cell line. HIV-specific Abs were employed to elicit ADCP of beads coated with HIV envelope protein. Overall, trends were noted among neutrophil donors and the ADCP profile was different from that of THP-1 cells. mAb ELISA titers correlated with ADCP by THP-1 cells but not neutrophils. Monoclonal (m)Abs were also tested with primary monocytes. Donor-to-donor variation was high, and hindered the analysis of this dataset, but it was, in itself, an important finding. This study illustrates the concept that the assessment of FcR-mediated Ab activity with a frequently used cell line such as THP-1 is not necessarily indicative of relevant Ab functionality in vivo, and this calls for in-depth study of the properties of the HIV antibodies best-suited to eliciting antiviral activities by primary cells.
- A smart nanosensor for the detection of human immunodeficiency virus and associated cardiovascular and arthritis diseases using functionalized graphene-based transistors. [Journal Article]
- BBBiosens Bioelectron 2018 Dec 07; 126:792-799
- Human immunodeficiency virus (HIV), which isa worldwide public health issue, is commonly associated with cardiovascular disorders (CVDs) and rheumatoid arthritis (RA). A smart nanosensor was develope...
Human immunodeficiency virus (HIV), which isa worldwide public health issue, is commonly associated with cardiovascular disorders (CVDs) and rheumatoid arthritis (RA). A smart nanosensor was developed for the detection of HIV and its related diseases (CVDs and RA) using graphene-based field-effect transistors (FETs). In this study, amine-functionalized graphene (afG) was conjugated with antibodies [anti-p24 for HIV, anti-cardiac troponin 1 (anti-cTn1) for CVDs, and anti-cyclic citrullinated peptide (anti-CCP) for RA] to detect various biomarkers. The antibodies were covalently conjugated to afG via carbodiimide activation. The bioconjugate (graphene-antibody) was characterized by various biophysical techniques such as UV-Vis, Raman spectroscopy, scanning electron microscopy (SEM), and atomic force microscopy (AFM). The electrochemical performance of the sensor was evaluated with respect to changes in the resistance of the electrode surface due to the interaction of the antigen with its specific antibody. The developed sensor was highly sensitive and showed a linear response to p24, cTn1, and, CCP from 1 fg/mL to 1 μg/mL. The limit of detection (LOD) was 100 fg/mL for p24 and 10 fg/mL for cTn1 and CCP under standard optimized conditions. The graphene-based smart nanodevice demonstrated excellent performance; thus, it could be used for the on-site detection of HIV, CVD, and RA biomarkers in real samples.
- Patterns and trends of HPV-related cancers other than cervix in South Africa from 1994-2013. [Journal Article]
- CECancer Epidemiol 2018 Dec 14; 58:121-129
- CONCLUSIONS: Anal and vulval cancers have increased over the reporting period. There is need to continuously monitor trends of these cancers. Implementation of HPV vaccination could significantly reduce the burden of HPV-related cancers.
- Sera selected from national STI surveillance system shows Chlamydia trachomatis PgP3 antibody correlates with time since infection and number of previous infections. [Journal Article]
- PlosPLoS One 2018; 13(12):e0208652
- CONCLUSIONS: Seropositivity increased with cumulative number of infections, and decreased over time after diagnosis on the indirect ELISA, but not on the double-antigen ELISA. This is the first study to demonstrate the combined impact of number of chlamydia diagnoses, time since diagnosis, and specific ELISA on Pgp3 seropositivity. Our findings are being used to inform models estimating age-specific chlamydia incidence over time using serial population-representative serum sample collections, to enable accurate public health monitoring of chlamydia.
- Disclosure of HIV serostatus and condomless sex among men living with HIV/AIDS in Florida. [Journal Article]
- PlosPLoS One 2018; 13(12):e0207838
- Despite campaigns to increase safer sex practices, there are people living with HIV/AIDS (PLWH) who do not disclose their HIV status to sexual partners and engage in condomless sex. The purpose of th...
Despite campaigns to increase safer sex practices, there are people living with HIV/AIDS (PLWH) who do not disclose their HIV status to sexual partners and engage in condomless sex. The purpose of this research was to: 1) describe factors associated with disclosure of HIV status to sexual partners; and 2) determine if disclosure and/or receipt of prevention counseling are independently associated with condomless sex. We used the Florida Medical Monitoring Project to analyze data from 376 HIV positive men with more than one sexual partner. Results indicated that 55% consistently disclosed their HIV status to sexual partners, 30% inconsistently disclosed, 15% did not disclose, and 48% reported any condomless sex. The odds of having condomless sex was 3.3 (CI = 1.5, 7.3) times greater in men who disclosed to all partners. Results suggest that men who disclose are also those who are more likely to have condomless sex. More research is needed to better understand the complex nature of disclosure and sexual risk behaviors and how disclosure impacts sexual risk.
- HIV screening among patients seeking care at Xuanwu Hospital: A cross-sectional study in Beijing, China, 2011-2016. [Journal Article]
- PlosPLoS One 2018; 13(12):e0208008
- CONCLUSIONS: HIV screening in China's general hospitals needs to be improved. More focus should be placed on screening outpatients, especially in the dermatology and STI department, and young men.
- Quantitative RNAseq analysis of Ugandan KS tumors reveals KSHV gene expression dominated by transcription from the LTd downstream latency promoter. [Journal Article]
- PPPLoS Pathog 2018 Dec 17; 14(12):e1007441
- KSHV is endemic in Uganda and the HIV epidemic has dramatically increased the incidence of Kaposi sarcoma (KS). To investigate the role of KSHV in the development of KS, we obtained KS biopsies from ...
KSHV is endemic in Uganda and the HIV epidemic has dramatically increased the incidence of Kaposi sarcoma (KS). To investigate the role of KSHV in the development of KS, we obtained KS biopsies from ART-naïve, HIV-positive individuals in Uganda and analyzed the tumors using RNAseq to globally characterize the KSHV transcriptome. Phylogenetic analysis of ORF75 sequences from 23 tumors revealed 6 distinct genetic clusters with KSHV strains exhibiting M, N or P alleles. RNA reads mapping to specific unique coding sequence (UCDS) features were quantitated using a gene feature file previously developed to globally analyze and quantitate KSHV transcription in infected endothelial cells. A pattern of high level expression was detected in the KSHV latency region that was common to all KS tumors. The clear majority of transcription was derived from the downstream latency transcript promoter P3(LTd) flanking ORF72, with little evidence of transcription from the P1(LTc) latency promoter, which is constitutive in KSHV-infected lymphomas and tissue-culture cells. RNAseq data provided evidence of alternate P3(LTd) transcript editing, splicing and termination resulting in multiple gene products, with 90% of the P3(LTd) transcripts spliced to release the intronic source of the microRNAs K1-9 and 11. The spliced transcripts encode a regulatory uORF upstream of Kaposin A with alterations in intervening repeat sequences yielding novel or deleted Kaposin B/C-like sequences. Hierarchical clustering and PCA analysis of KSHV transcripts revealed three clusters of tumors with different latent and lytic gene expression profiles. Paradoxically, tumors with a latent phenotype had high levels of total KSHV transcription, while tumors with a lytic phenotype had low levels of total KSHV transcription. Morphologically distinct KS tumors from the same individual showed similar KSHV gene expression profiles suggesting that the tumor microenvironment and host response play important roles in the activation level of KSHV within the infected tumor cells.
- Voluntary medical male circumcision service delivery in South Africa: The economic costs and potential opportunity for private sector involvement. [Journal Article]
- PlosPLoS One 2018; 13(12):e0208698
- CONCLUSIONS: The private sector VMMC unit cost ($137) did not differ substantially from that at government and PEPFAR-supported facilities ($132 based on results from a similar study conducted in 2014 in South Africa at 33 sites across eight of the countries nine provinces). The two largest cost drivers, consumables and direct labor, were comparable across the two studies (75% in private facilities and 67% in public/PEPFAR-supported facilities). Results from this study provide VMMC unit cost data that had been missing and makes an important contribution to a better understanding of the costs of VMMC service delivery, enabling VMMC programs to make informed decisions regarding funding levels and scale-up strategies for VMMC in South Africa.
- Hepatitis E virus seroprevalence and determinants in various study populations in the Netherlands. [Journal Article]
- PlosPLoS One 2018; 13(12):e0208522
- CONCLUSIONS: Vegetarians were significantly less often HEV seropositive. Ethnic origin influenced the risk for being IgG HEV seropositive. MSM and PWUD were not at higher risk for being IgG HEV seropositive than blood donors.
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- The adjuvant AlhydroGel elicits higher antibody titres than AddaVax when combined with HIV-1 subtype C gp140 from CAP256. [Journal Article]
- PlosPLoS One 2018; 13(12):e0208310
- With the HIV-1 epidemic in southern Africa still rising, a prophylactic vaccine against the region's most prolific subtype (subtype C) would be a significant step forward. In this paper we report on ...
With the HIV-1 epidemic in southern Africa still rising, a prophylactic vaccine against the region's most prolific subtype (subtype C) would be a significant step forward. In this paper we report on the effect of 2 different adjuvants, AddaVax and AlhydroGel, formulated with HIV-1 subtype C gp140, on the development of binding and neutralising antibody titres in rabbits. AddaVax is a squalene-based oil-in-water nano-emulsion (similar to MF59) which can enhance both cellular and humoral immune responses, whilst AlhydroGel (aluminium hydroxide gel) mainly drives a Th2 response. The gp140 gene tested was derived from the superinfecting virus (SU) from participant CAP256 in the CAPRISA 002 Acute infection cohort. The furin cleavage site of the Env protein was replaced with a flexible linker and an I559P mutation introduced. Lectin affinity purified soluble Env protein was mainly trimeric as judged by molecular weight using BN-PAGE and contained intact broadly neutralising epitopes for the V3-glycan supersite (monoclonal antibodies PGT128 and PGT135), the CD4 binding site (VRC01) and the V2-glycan (PG9) but not for the trimer-specific monoclonal antibodies PG16, PGT145 and CAP256-VRC26_08. When this soluble Env protein was tested in rabbits, AlhydroGel significantly enhanced soluble Env and V1V2 binding antibodies when compared to AddaVax. Finally, AlhydroGel resulted in significantly higher neutralization titres for a subtype C Tier 1A virus (MW965.26) and increased neutralization breadth to Tier 1A and 1B viruses. However, no autologous Tier 2 neutralisation was observed. These data suggest that adjuvant selection is critical for developing a successful vaccine and AlhydroGel should be further investigated. Additional purification of trimeric native-like CAP256 Env and/or priming with DNA or MVA might enhance the induction of neutralizing antibodies and possible Tier 2 HIV-1 neutralisation.