Publications by authors named "Paolo Palma"

mRNA vaccines demonstrate impaired immunogenicity and durability in vulnerable older populations. We hypothesized that human modeling and proteomics could elucidate age-specific mRNA vaccine actions. BNT162b2-stimulation changed the plasma proteome of blood samples from young (18-50Y) and older adult (≥60Y) participants, assessed by mass spectrometry, proximity extension assay, and multiplex.

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In this work our aim was to identify early biomarkers in plasma samples associated with mortality in children with perinatal HIV treated early in life, to potentially inform early intervention targeting this vulnerable group. 20/215 children (9.3%) with perinatal HIV, enrolled within 3 months of age died prematurely within the first year of the study, despite early ART initiation.

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Article Synopsis
  • The study examined outcomes for infants with perinatally-acquired HIV who started early ART in South Africa, Mozambique, and Mali, focusing on mortality, viral suppression, and engagement in care over three years.
  • Out of 215 infants monitored, the 1-year death probability was 10%, which rose to 12% by the second and third years, with high baseline viral load identified as a significant risk factor for mortality.
  • Of the children, only 42% maintained sustained viral control for a year, with adherence to ART deemed optimal in 81% of visits, although lower adherence was linked to female sex at birth, younger diagnosis age, and adverse maternal social circumstances.
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  • Despite ongoing antiretroviral therapy, many adolescents and young adults with perinatally acquired HIV are experiencing signs of premature aging and associated health issues, leading to the necessity of studying aging biomarkers and their link to the HIV reservoir.* -
  • A study involving 55 adolescents and young adults showed they had higher rates of certain activated immune cells and inflammatory markers compared to healthy peers, alongside shorter telomeres, indicating faster aging processes.* -
  • The participants were categorized based on their viral suppression status, revealing that those who started ART early (Early Suppressed) had fewer signs of aging and inflammation compared to those who started later, stressing the critical role of early treatment in improving health outcomes.*
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Despite progress, the molecular mechanisms underlying Kawasaki Disease (KD) and intravenous immunoglobulin's (IVIG) ability to mitigate the inflammatory process remain poorly understood. To characterize this condition, plasma proteomic profiles, flow cytometry, and gene expression of T cell subsets were investigated in longitudinal samples from KD patients and compared with two control groups. Systems-level analysis of samples in the acute phase revealed distinctive inflammatory features of KD, involving mainly Th-1 and Th-17 mediators and unveiled a potential disease severity signature.

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Background: The first year of life is a period of rapid immune development that can impact health trajectories and the risk of developing respiratory-related diseases, such as asthma, recurrent infections, and eczema. However, the biology underlying subsequent disease development remains unknown.

Methods: Using weighted gene correlation network analysis (WGCNA), we derived modules of highly correlated immune-related proteins in plasma samples from children at age 1 year (N=294) from the Vitamin D Antenatal Asthma Reduction Trial (VDAART).

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  • Researchers studied 284 young children in South Africa who started HIV treatment early to see how well they could control the virus after treatment.
  • About 84% of these kids managed to hide the virus while on treatment, but only 32% were still virus-free after more than 3 years.
  • Some boys were able to stay virus-free even after stopping their treatment for months, which might be linked to differences in how boys and girls' immune systems respond to the virus.
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  • Human cytomegalovirus (CMV) is a common virus that causes lifelong infection and is a key cause of congenital infections in newborns worldwide.
  • Researchers studied the behavior of natural killer (NK) cells in mothers and newborns, comparing those who transmitted the virus to those who did not.
  • The study found that non-transmitting mothers and their congenital CMV-infected babies had different NK cell profiles, which could help predict the risk of virus transmission during pregnancy.
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  • Children with perinatally acquired HIV (PHIV) have unique vaccination needs due to their less effective immune responses compared to healthy controls (HCs).
  • A study evaluated the safety and effectiveness of a meningococcal vaccine in both PHIV-affected children and HCs, finding that while the vaccine was safe for both groups, PHIV showed lower immune responses.
  • Further analysis revealed differences in B cell behavior and gene expression between PHIV children and HCs post-vaccination, indicating that PHIV may have different mechanisms affecting long-term immunity, warranting more research in these vulnerable groups.
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The Lancet PROSPECT Trial has shown that vaginal repair has dismal cure rates of some 20% at 12 months. Meanwhile 10-year data from collagen creating ligament repair methods (implanted mini-sling tapes), with no vaginal excision, report very high, long-term cure rates. The reason for conserving the vagina, is that the vagina's main function is to transmit the muscle forces for external urethral closure or opening.

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The Integral Theory Paradigm (ITP) has a 25-year track record of successfully treating bladder/bowel/pain symptoms caused by laxity in specific ligaments, even when the prolapse is minimal. The ITP-based treatment involves ligament support and can be nonsurgical or daycare surgical. An accurate diagnostic protocol is required.

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Midurethral slings (MUS) have revolutionized the treatment of stress urinary incontinence (SUI). MUS operations work by creating a collagenous pubourethral ligament (PUL). Since 1996, more than 10 million operations have been performed worldwide.

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In perinatal HIV infection, early antiretroviral therapy (ART) initiation is recommended but questions remain regarding infant immune responses to HIV and its impact on immune development. Using single cell transcriptional and phenotypic analysis we evaluated the T cell compartment at pre-ART initiation of infants with perinatally acquired HIV from Maputo, Mozambique (Towards AIDS Remission Approaches cohort). CD8 T cell maturation subsets exhibited altered distribution in HIV exposed infected (HEI) infants relative to HIV exposed uninfected infants with reduced naive, increased effectors, higher frequencies of activated T cells, and lower frequencies of cells with markers of self-renewal.

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Article Synopsis
  • The study investigates the levels of HIV RNA and cytokines in adolescents who have been on antiretroviral treatment (ART) since early in life, focusing on potential indicators for clinical trials aimed at finding a cure for HIV.
  • It enrolled 40 perinatally infected adolescents on ART for over 5 years, measuring various HIV markers and correlating them with clinical characteristics.
  • Results show that lower levels of cell-associated RNA (CA-RNA) are linked to lower levels of cell-associated DNA (CA-DNA), and that undetectable CA-RNA is associated with factors like earlier initiation of ART and higher Western Blot scores.
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  • The study examines how both distal (external) and proximal (internal) stressors affect alcohol use among gay, bisexual, and other men who have sex with men (GBM), considering the impact of anxiety and depression as mediators.
  • Researchers analyzed data from 2,449 GBM across major Canadian cities, using advanced statistical methods to identify relationships between stressors, mental health, and alcohol consumption.
  • The findings indicate that while distal stress leads to increased proximal stress and mental health issues, the direct effects on alcohol use are more complex, with anxiety and depression playing differing roles in alcohol consumption and problems.
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  • Positive attitudes towards HIV treatment among gay, bisexual, and other men who have sex with men (GBM) may lead to riskier sexual behaviors that increase the chances of bacterial STIs.
  • A study involving 2449 GBM discovered a direct link between favorable HIV treatment attitudes and higher rates of current STI diagnoses, particularly through pathways of having more male anal sex partners and engaging in condomless anal sex.
  • The findings stress the need for healthcare providers to educate GBM about the risks attached to these attitudes in order to improve sexual health counseling, testing, and prevention strategies.
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Introduction: Since the beginning of the SARS-CoV-2 pandemic in early 2020, it has been apparent that children were partially protected from both infection and the more severe forms of the disease. Many different mechanisms have been proposed to explain this phenomenon, including children's frequent exposure to other upper respiratory infections and vaccines, and which inflammatory cytokines they are more likely to produce in response to infection. Furthermore, given the presence of SARS-CoV-2 in the intestine and its ability to infect enterocytes, combined with the well described immunomodulatory capabilities of the microbiome, another potential contributing factor may be the presence of certain protective microbial members of the gut microbiota (GM).

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Introduction: The gut microbiota (GM) play a significant role in the infectivity and severity of COVID-19 infection. However, the available literature primarily focuses on adult patients and it is known that the microbiota undergoes changes throughout the lifespan, with significant alterations occurring during infancy and subsequently stabilizing during adulthood. Moreover, children have exhibited milder symptoms of COVID-19 disease, which has been associated with the abundance of certain protective bacteria.

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The human immune system is a complex network of coordinated components that are crucial for health and disease. Animal models, commonly used to study immunomodulatory agents, are limited by species-specific differences, low throughput, and ethical concerns. In contrast, in vitro modeling of human immune responses can enable species- and population-specific mechanistic studies and translational development within the same study participant.

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Background And Objectives: mRNA vaccines elicit a durable humoral response to SARS-CoV-2 in adults, whereas evidence in children is scarce. This study aimed to assess the early and long-term immune response to the mRNA vaccine in children with or without previous SARS-CoV-2 infection.

Methods: In a multicentre prospective observational study, we profiled the immune response to the Pfizer BioNTech (BNT162b2) vaccine in 5-11-year-old children attending the University Pediatric Hospital of Padua and Bambino-Gesù Hospital in Rome (Italy) from December-2021 to February-2023.

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