Evolution of HIV-1 subtype C immune responses during acute and chronic HIV infection

The aim of this study was to compare the magnitude and breadth of HIV-specific T cell responses to HIV Gag and Nef mounted during acute HIV infection with those that emerged during chronic infection and to investigate the association of these responses with subsequent HIV disease progression (CD4 counts and plasma viral loads)

In Silico Characterisation of Putative Prophages in Lactobacillaceae Used in Probiotics for Vaginal Health

While live biotherapeutics offer a promising approach to optimizing vaginal microbiota, the presence of functional prophages within introduced Lactobacillaceae strains could impact their safety and efficacy. We evaluated the presence of prophages in 895 publicly available Lactobacillaceae genomes using Phaster, Phigaro, Phispy, Prophet and Virsorter. Prophages were identified according to stringent (detected by ≥4 methods) or lenient criteria (detected by ≥2 methods), both with >80% reciprocal sequence overlap. The stringent approach identified 448 prophages within 359 genomes, with 40.1% genomes harbouring at least one prophage, while the lenient approach identified 1671 prophages within 83.7% of the genomes. To confirm our in silico estimates in vitro, we tested for inducible prophages in 57 vaginally-derived and commercial Lactobacillaceae isolates and found inducible prophages in 61.4% of the isolates. We characterised the in silico predicted prophages based on weighted gene repertoire relatedness and found that most belonged to the Siphoviridae or Myoviridae families. ResFam and eggNOG identified four potential antimicrobial resistance genes within the predicted prophages. Our results suggest that while Lactobacillaceae prophages seldomly carry clinically concerning genes and thus unlikely a pose a direct risk to human vaginal microbiomes, their high prevalence warrants the characterisation of Lactobacillaceae prophages in live biotherapeutics

Inflammatory Cytokine Profiles of Semen Influence Cytokine Responses of Cervicovaginal Epithelial Cells

Genital inflammatory cytokine responses increase HIV risk. Since male partner semen is a complex mixture of immune-modulatory prostaglandins and cytokines, we hypothesized that exposure to semen may influence genital inflammation in women. Here, we investigated cytokine response kinetics of cervical cells following stimulation with seminal plasma from HIV-negative and HIV-positive men characterized as having low or high concentrations of inflammatory cytokines. Irrespective of the HIV status or semen cytokine profile, in vitro stimulation of cervical cells with seminal plasma resulted in significantly elevated concentrations of secreted IL-6, IL-8, TNF-β, MCP-1, GM-CSF, and VEGF within 8 h of stimulation, which tended to decline by 24 h, although this was only significant for TNF-β. Consistent with this, cervical cells responded to seminal plasma with increases in IL-8 and IL-1β mRNA expression of 10-fold. These findings suggest that the impact of semen on local female genital cytokines is likely transient. Although these findings suggest that the impact of semen on local female genital cytokines may not be sustained long-term, this heightened genital inflammation may have implications for HIV risk in women

Inflammatory cytokine biomarkers to identify women with asymptomatic sexually transmitted infections and bacterial vaginosis who are at high risk of HIV infection.

CAPRISA, 2016.Abstract available in pdf

Correction to: Microbial function and genital inflammation in young South African women at high risk of HIV infection

Correction to: Microbiome 8, 165 (2020) https://doi.org/10.1186/s40168-020-00932-

In Silico Characterisation of Putative Prophages in Lactobacillaceae Used in Probiotics for Vaginal Health

International audienceWhile live biotherapeutics offer a promising approach to optimizing vaginal microbiota, the presence of functional prophages within introduced Lactobacillaceae strains could impact their safety and efficacy. We evaluated the presence of prophages in 895 publicly available Lactobacillaceae genomes using Phaster, Phigaro, Phispy, Prophet and Virsorter. Prophages were identified according to stringent (detected by ≥4 methods) or lenient criteria (detected by ≥2 methods), both with >80% reciprocal sequence overlap. The stringent approach identified 448 prophages within 359 genomes, with 40.1% genomes harbouring at least one prophage, while the lenient approach identified 1671 prophages within 83.7% of the genomes. To confirm our in silico estimates in vitro, we tested for inducible prophages in 57 vaginally-derived and commercial Lactobacillaceae isolates and found inducible prophages in 61.4% of the isolates. We characterised the in silico predicted prophages based on weighted gene repertoire relatedness and found that most belonged to the Siphoviridae or Myoviridae families. ResFam and eggNOG identified four potential antimicrobial resistance genes within the predicted prophages. Our results suggest that while Lactobacillaceae prophages seldomly carry clinically concerning genes and thus unlikely a pose a direct risk to human vaginal microbiomes, their high prevalence warrants the characterisation of Lactobacillaceae prophages in live biotherapeutics

Delaying BCG vaccination until 8 weeks of age results in robust BCG-specific T-cell responses in HIV-exposed infants

Background: BCG vaccination prevents disseminated tuberculosis in children, but it is contraindicated for persons with human immunodeficiency virus (HIV) infection because it can result in severe disease in this population. In tuberculosis-endemic regions, BCG vaccine is administered soon after birth, before in utero and peripartum HIV infection is excluded. We therefore assessed the immunogenicity of BCG vaccine in HIV-exposed infants who received BCG at birth or at 8 weeks of age. Methods: HIV-exposed, uninfected infants were randomly assigned to receive BCG vaccination at birth (the early vaccination arm) or 8 weeks of age (the delayed vaccination arm). BCG-specific proliferative and intracellular cytokine responses were assessed in 28 infants per arm at 6, 8, and 14 weeks of life. Results: There was no difference in BCG-specific T-cell proliferation between the study arms 6 weeks after vaccination. However, at 14 weeks of age, the frequency of interferon γ-expressing CD4+ T cells and multifunctional BCG-specific responses in the delayed vaccinated arm were significantly higher than those in the early vaccination arm (P =. 021 and P =. 011, respectively). Conclusions.The immunogenicity of BCG vaccination in HIV-exposed, uninfected infants is not compromised when delayed until 8 weeks of age and results in robust BCG-specific T-cell responses at 14 weeks of age. These findings support further evaluation of this modified BCG vaccination strategy for HIV-exposed infants. Clinical Trials Registration.NCT02062580

Defining genital tract cytokine signatures of sexually transmitted infections and bacterial vaginosis in women at high risk of HIV infection: A cross-sectional study

Objectives: Sexually transmitted infections (STI) and bacterial vaginosis (BV) cause female genital tract inflammation. This inflammation, which is often present in the absence of symptoms, is associated with increased susceptibility to HIV infection. We aimed to evaluate genital cytokine profiles and the degree of inflammation associated with common STIs and BV

Exploring potential of vaginal Lactobacillus isolates from South African women for enhancing treatment for bacterial vaginosis

International audienceAntibiotics continue to be the standard-of-care for bacterial vaginosis (BV), although recurrence rates are high. Vaginal probiotics may improve durability of BV treatment, although few probiotics for vaginal health contain Lactobacillus spp. that commonly colonize the lower female genital tract. Characteristics of vaginal Lactobacillus strains from South African women were evaluated for their probiotic potential in vitro compared to strains from commercial vaginal products, including growth at varying pHs, ability to lower pH, produce D-/L-lactate and H 2 O 2 , influence growth of BV-associated Gardnerella vaginalis and Prevotella bivia, adherence to cervical cells and susceptibility to antibiotics. Fifty-seven Lactobacillus strains were purified from cervico-vaginal fluid, including L. crispatus, L. jensenii, L. gasseri, L. mucosae, and L. vaginalis. L crispatus strains grew better at pHs below 4.5 and lowered pH more effectively than other strains. Production of D-/L-lactate and H 2 O 2 varied between Lactobacillus species and strains. Lactobacillus strains generally inhibited P. bivia more uniformly than G. vaginalis isolates. All vaginal Lactobacillus isolates were resistant to metronidazole while susceptibility to clindamycin varied. Furthermore, vaginal Lactobacillus strains tended to be broadly susceptible to penicillin, amoxicillin, rifampicin and rifabutin. Whole-genome-sequencing of five of the best-performing vaginal Lactobacillus strains confirmed their likely safety, due to antimicrobial resistance elements being largely absent, while putative intact prophages were present in the genomes of two of the five strains. Overall, vaginal Lactobacillus strains largely performed better in these in vitro assays than probiotic strains currently used in probiotics for vaginal health. Including the best-performing vaginal Lactobacillus isolates in a regionspecific probiotic for vaginal health may result in improved BV treatment options.Les antibiotiques restent la norme en matière de traitement de la vaginose bactérienne (VB), bien que les taux de récurrence soient élevés. Les probiotiques vaginaux peuvent améliorer la durabilité du traitement de la VB, bien que peu de probiotiques pour la santé vaginale contiennent des Lactobacillus spp. qui colonisent couramment le tractus génital féminin inférieur. Les caractéristiques des souches vaginales de Lactobacillus des femmes sud-africaines ont été évaluées in vitro pour leur potentiel probiotique par rapport aux souches de produits vaginaux commerciaux, notamment la croissance à des pH variables, la capacité à abaisser le pH, à produire du D-/L-lactate et du H 2 O 2 , l'influence sur la croissance de Gardnerella vaginalis et Prevotella bivia associés à la BV, l'adhérence aux cellules cervicales et la sensibilité aux antibiotiques. Cinquante-sept souches de Lactobacillus ont été purifiées du liquide cervico-vaginal, dont L. crispatus, L. jensenii, L. gasseri, L. mucosae et L. vaginalis. Les souches de L. crispatus se développent mieux à des pH inférieurs à 4,5 et abaissent le pH plus efficacement que les autres souches. La production de D-/L-lactate et de H 2 O 2 a varié entre les espèces et les souches de Lactobacillus. Les souches de Lactobacillus inhibaient généralement P. bivia de manière plus uniforme que les isolats de G. vaginalis. Tous les isolats vaginaux de Lactobacillus étaient résistants au métronidazole, tandis que la sensibilité à la clindamycine variait. En outre, les souches vaginales de Lactobacillus avaient tendance à être largement sensibles à la pénicilline, à l'amoxicilline, à la rifampicine et à la rifabutine. Le séquençage du génome entier de cinq des souches vaginales de Lactobacillus les plus performantes a confirmé leur innocuité probable, en raison de l'absence quasi-totale d'éléments de résistance aux antimicrobiens, tandis que des prophètes présumés intacts étaient présents dans les génomes de deux des cinq souches. Dans l'ensemble, les souches vaginales de Lactobacillus ont obtenu de meilleurs résultats dans ces essais in vitro que les souches probiotiques actuellement utilisées dans les probiotiques pour la santé vaginale. L'inclusion des isolats de Lactobacillus vaginaux les plus performants dans un probiotique spécifique à une région pour la santé vaginale pourrait permettre d'améliorer les options de traitement de la BV