Abstract Autoantibody profiles in HIV-associated pulmonary arterial hypertension (HIV-PAH) remain poorly characterized. Using a validated proteomic pipeline (two-dimensional immunoblot, mass spectrometry, ELISA), we compared 20 HIV-PAH patients with 20 HIV controls without PAH. Anti-annexin A5 (AnxA5) autoantibodies were present in 55% of HIV-PAH patients versus 0% of controls (P < .001) and anti-14-3-3ε in 35% versus 5% (P = .04), despite comparable HIV duration, CD4 counts, and virological control. Both remained associated with PAH after adjustment for coinfections. These autoantibodies mirror those described in connective-tissue-disease-PAH, suggesting a possible overlap in autoimmune features and a research biomarker warranting prospective validation.
Abstract Background Naturally acquired antibodies to Chlamydia trachomatis (CT) are associated with reduced cervical bacterial burden but not with protection from endometrial or subsequent CT infection. We investigated whether antibody-mediated opsonophagocytosis, a functional measure of humoral immunity, was associated with protection against these clinical outcomes. Methods Serum samples from 139 women enrolled in the longitudinal T-cell Response Against Chlamydia (TRAC) cohort and 11 healthy seronegative controls were evaluated for Fc receptor–mediated opsonophagocytosis of CellTrace violet-labeled CT elementary bodies using Tohoku Hospital Pediatrics-1 monocytes. Associations with antichlamydial antibody titers, cervical bacterial burden, endometrial infection, and incident CT infection during 12 months of follow-up were assessed. Results Opsonophagocytic activity correlated strongly with antichlamydial antibody titers and was significantly higher in seropositive women than in seronegative controls. Although a weak inverse correlation with cervical bacterial burden was observed, neither the proportion of phagocytic cells nor the extent of bacterial uptake was associated with reduced endometrial infection. Similarly, neither measure differed between women who experienced incident CT infection during follow-up and those who remained infection-free. Conclusions Naturally acquired antichlamydial antibodies promoted Fc receptor–mediated uptake of CT; however, antibody-mediated opsonophagocytic activity was not associated with protection from endometrial or subsequent CT infection. These findings suggest that naturally acquired antibody-mediated opsonophagocytic activity is unlikely to serve as a correlate of protection against CT infection.
Abstract Background A respiratory syncytial virus (RSV) vaccine, eliciting active immunity could significantly impact child health. This study evaluated 3 intranasal live-attenuated candidate RSV vaccines, RSV/ΔNS2/Δ1313/I1314L, RSV/6120/ΔNS2/1030s, and RSV/276 to placebo. Methods Healthy, RSV-seronegative children aged 6–24 monthswere randomized to receive 1 of 3 candidate vaccines or placebo. Participants were monitored for vaccine reactogenicity and RSV serum antibodies. Results Between years 2019 and 2023, 67 participants were randomized, 20 each to RSV/ΔNS2/Δ1313/I1314L, RSV/6120/ΔNS2/1030s, and placebo and 7 to RSV/276. The RSV/276 arm closed early due to an excess of mild cough in another study. The proportion (95% CI) of children experiencing at least 1 solicited adverse event during the 28 days after inoculation was 55% (32%, 77%) in RSV/ΔNS2/Δ1313/I1314L, 40% (19%, 64%) in RSV/6120/ΔNS2/1030s, 71% (29%, 96%) in RSV/276, and 55% (32%, 77%) in placebo. Events were mostly Grade 1 and often associated with other viruses. The proportion of children with ≥4-fold increase in serum RSV-neutralizing antibody titer in each vaccine arm (>70%) was significantly greater than the placebo arm (15%). Conclusions RSV/ΔNS2/Δ1313/I1314L and RSV/6120/ΔNS2/1030s had excellent safety and immunogenicity;assessment of RSV/276 was limited by the small sample size. RSV/ΔNS2/Δ1313/I1314L and RSV/6120/ΔNS2/1030s were deemed suitable for further evaluation. Clinical Trials Registration NCT03916185.
Abstract Background Differentiating wild and vaccine measles virus (MeV) strains is critical for appropriate healthcare response during outbreak vaccination campaigns. Sequencing, the current standard, is expensive, time-consuming, and limited to specialized laboratories. We developed and implemented a novel differential MeV RT-qPCR assay to address these challenges, which we describe herein. Methods We designed a differential two-step assay; the first step, termed MRRV, distinguishes between rubella, wild MeV, and vaccine MeV. The second, termed “MeV differential”, differentiates between genotypes A (vaccine), B and D. Results The assay detects 10-50 copies per reaction and accurately classifies weak clinical samples (Cq > 32), with 100% accuracy, compared with the N gene sequencing gold standard. Evaluated on over 4,000 clinical samples retrospectively and during the 2025-2026MeV outbreak in Israel, the assay revealed that ∼9% of tested originated from vaccine strain. Among tested municipalities, those running active vaccination campaigns had significantly higher vaccine strain detections (>10 cases each) than those with routine vaccination (1-2 cases). Retrospective analysis of samples from 2018-2024 identified a mix of B and D strains. The novel assay successfully identified double infection cases (exposure to a wild strain shortly before or after vaccination). Conclusion The novel assay proved useful both as a diagnostic tool that enables focused, efficient healthcare response, and as an epidemiological tool that provides valuable information in real-time. This assay is faster, cheaper and more amendable for high throughput testing, compared with the gold-standard sequencing classification.
Abstract Background People with HIV (PWH) in sub-Saharan Africa remain at high risk of pneumococcal carriage and disease, despite effective antiretroviral therapy. Understanding the immune factors driving this is key to addressing the issue. Methods Virally suppressed, clinically stable PWH (n = 60) and HIV-uninfected adults (n = 60) underwent intranasal challenge with live pneumococcus serotype 6B. Experimental carriage was determined by culture and serotyping of nasal wash samples. Pneumococcal capsular and whole-cell IgG in nasal wash and serum samples were measured by ELISA. Antibody binding was measured using a flow cytometry assay. Results Baseline pneumococcal capsular IgG, whole-cell IgG, and antibody binding were similar between PWH and HIV-uninfected participants. Challenge did not increase IgG concentration in either group. Carriage susceptibility among PWH was associated with lower baseline serum capsular 6B IgG (0.84 vs 2.33 µg/mL, p < 0.01), lower nasal capsular 6B IgG (328 vs 761 pg/mL, p = 0.07), and lower nasal whole-cell IgG (92.2 vs 205 AU/mL, p = 0.02). These associations were not observed in HIV-uninfected participants. Carriage in HIV-uninfected participants was associated with an increase in IgG binding from baseline to day 21 (120 vs 209 AU, Friedman χ2 = 11.1, p = 0.004), which was not detected in PWH (79.2 vs 72.3 AU, χ2 = 0.67, p = 0.72)). Conclusion Baseline pneumococcal IgG levels and function were similar in PWH and HIV-uninfected participants. However, experimental challenge revealed specific differences in humoral correlates of pneumococcal carriage between PWH and HIV-uninfected adults. These findings support evaluation of vaccination strategies to enhance pneumococcal antibody concentration and function in PWH in sub-Saharan Africa.
