Biology subjects

Aldrovandi, G.

Publications and source records attributed to Aldrovandi, G..

3 recordsLinked to original sources

bioRxiv2025

Gut microbiome associations with poliovirus vaccine seroconversion in children in the Democratic Republic of the Congo

BackgroundDespite efforts to increase global immunization, vaccination seroconversion in low and middle income countries (LMICs) is often lower than in high income countries (HICs). The reasons for this disparity are not fully understood. Given the role of the gut microbiome in immune development, we investigated the relationship between the gut microbiome and polio vaccine seroconversion in children in the Democratic Republic of the Congo (DRC). MethodsThis cross-sectional analysis included children ages 6-24 months old (n=90) enrolled in the DRC. Vaccine history was obtained from health records and/or self-report and poliovirus serostatus surveyed using dried blood spots. Nutritional status was evaluated using anthropomorphic measures. Microbiome profiling (16S rRNA gene) was performed and associations with poliovirus serostatus and malnutrition were examined. ResultsThe average age of the study population was 13.6 months (SD=5.6) with 58% female. Poliovirus seropositivity was 65.5% and 22% of the children were malnourished. We found that presence of Campylobacter and Veillonella, especially at an early age, was associated with low poliovirus vaccination seroconversion. These bacterial taxa differed from those associated with malnutrition. ConclusionsThe presence of enteropathogens such as Campylobacter at a young age could be an important factor contributing to low vaccination seroconversion in children in LMICs.

microbiology↗

bioRxiv2024

Natural Variation in HIV-1 Entry Kinetics Map to Specific Residues and Reveal an Interdependence Between Attachment and Fusion

HIV-1 entry kinetics reflect the fluid motion of the HIV envelope glycoprotein through at least three major structural configurations that drive virus-cell membrane fusion. The lifetime of each state is an important component of potency for inhibitors that target them. We used the time-of-addition inhibitor assay and a novel analytical strategy to define the kinetics of pre-hairpin exposure (using T20) and co-receptor engagement (via. maraviroc), through a characteristic delay metric, across a variety of naturally occurring HIV Env isolates. Among 257 distinct HIV-1 envelope isolates we found a remarkable breadth of T20 and maraviroc delays ranging from as early as 30 seconds to as late as 60 minutes. The most extreme delays were observed among transmission-linked clade C isolates. We identified four single-residue determinants of late T20 and maraviroc delays that are associated with either receptor engagement or gp41 function. Comparison of these delays with T20 sensitivity suggest co-receptor engagement and fusogenic activity in gp41 act cooperatively but sequentially to drive entry. Our findings support current models of entry where co-receptor engagement drives gp41 eclipse and have strong implications for the design of entry inhibitors and antibodies that target transient entry states. Author Summary.The first step of HIV-1 infection is entry, where virus-cell membrane fusion is driven by the HIV-1 envelope glycoprotein through a series of conformational changes. Some of the most broadly active entry inhibitors work by binding conformations that exist only transiently during entry. The lifetimes of these states and the kinetics of entry are important elements of inhibitor activity for which little is known. We demonstrate a remarkable range of kinetics among 257 diverse HIV-1 isolates and find that this phenotype is highly flexible, with multiple single-residue determinants. Examination of the kinetics of two conformational landmarks shed light on novel kinetic features that offer new details about the role of co-receptor engagement and provide a framework to explain entry inhibitor synergy.

molecular biology↗

bioRxiv2022

Hybrid immunity shifts the Fc-effector quality of SARS-CoV-2 mRNA vaccine-induced immunity

Despite the robust immunogenicity of SARS-CoV-2 mRNA vaccines, emerging data reveal enhanced neutralizing antibody and T cell cross-reactivity among individuals that previously experienced COVID-19, pointing to a hybrid immune advantage with infection-associated immune priming. Beyond neutralizing antibodies and T cell immunity, mounting data point to a potential role for additional antibody effector functions, including opsinophagocytic activity, in the resolution of symptomatic COVID-19. Whether hybrid immunity modifies the Fc-effector profile of the mRNA vaccine-induced immune response remains incompletely understood. Thus, here we profiled the SARS-CoV-2 specific humoral immune response in a group of individuals with and without prior COVID-19. As expected, hybrid Spike-specific antibody titers were enhanced following the primary dose of the mRNA vaccine, but were similar to those achieved by naive vaccinees after the second mRNA vaccine dose. Conversely, Spike-specific vaccine-induced Fc-receptor binding antibody levels were higher after the primary immunization in individuals with prior COVID-19, and remained higher following the second dose compared to naive individuals, suggestive of a selective improvement in the quality, rather than the quantity, of the hybrid humoral immune response. Thus, while the magnitude of antibody titers alone may suggest that any two antigen exposures - either hybrid immunity or two doses of vaccine alone - represent a comparable prime/boost immunologic education, we find that hybrid immunity offers a qualitatively improved antibody response able to better leverage Fc effector functions against conserved regions of the virus.

immunology↗