Molecular and Immunological Characterization of Staphylococcus aureus in Pediatric Atopic Dermatitis: Implications for Prophylaxis and Clinical Management

S. aureus represents a critical cofactor in atopic dermatitis (AD). In this paper, the prevalence of S. aureus infection/colonization was evaluated in 117 children as well as in their cohabitants, in order to assess the value of S. aureus characterization in predicting disease onset and severity and in providing indications for prophylaxis. Results showed that children with AD as well as their cohabitants had a significantly greater incidence of S. aureus infection/colonization as compared to controls. The genetic characterization showed a virtual identity of the bacteria strains collected at different sites of the patients with those found in the cohabitants, suggesting both a direct transmission between the nasal reservoir and the lesions in the same atopic subject and a risk for reinfection within family cohabitants. These data stress the need of preliminary laboratory assessment and posttherapy control in both AD patients and their close contacts for effective S. aureus eradication

Global antibiotic use during the COVID-19 pandemic: Analysis of pharmaceutical sales data from 71 countries, 2020–2022

Background: Despite bacterial coinfection rates of less than 10%, antibiotics are prescribed to an estimated 75% of patients with COVID-19, potentially exacerbating antimicrobial resistance. We estimated the associations of COVID-19 cases and vaccinations with global antibiotic sales during the first two years of the COVID-19 pandemic. Methods: We obtained monthly data on broad-spectrum antibiotic sales volumes (cephalosporins, penicillins, macrolides, and tetracyclines) in 71 countries during March 2020–May 2022 from the IQVIA MIDAS® database. These data were combined with country-month-level COVID-19 case and vaccination data from Our World in Data. We used least squares (pooled) and fixed-effects panel data regression models, accounting for country characteristics, to estimate the associations between antibiotic sales volumes and COVID-19 cases and vaccinations per 1000 people. Findings: Sales of all four antibiotics fell sharply during April and May 2020, followed by a gradual rise to near pre-pandemic levels through May 2022. In fixed-effects regression models, a 10% increase in monthly COVID-19 cases was associated with 0.2%–0.3% higher sales of cephalosporins, 0.2%–0.3% higher sales of penicillins, 0.4%–0.6% higher sales of macrolides, and 0.3% higher sales of all four antibiotics combined per 1000 people. Across continents, a 10% increase in monthly COVID-19 cases was associated with 0.8%, 1.3%, and 1.5% higher macrolides sales in Europe, North America, and Africa respectively. Sales of other antibiotics across continent were also positively associated with COVID-19 cases, although the estimated associations were smaller in magnitude. No consistent associations were observed between antibiotic sales and COVID-19 vaccinations. Results from pooled regression analysis were similar to those from the fixed-effects models. Interpretation: Antibiotic sales were positively associated with COVID-19 cases globally during 2020–2022. Our findings underline that antibiotic stewardship in the context of COVID-19 remains essential. Funding: Bill & Melinda Gates Foundation

Transforming vaccine development

The urgency to develop vaccines against Covid-19 is putting pressure on the long and expensive development timelines that are normally required for development of lifesaving vaccines. There is a unique opportunity to take advantage of new technologies, the smart and flexible design of clinical trials, and evolving regulatory science to speed up vaccine development against Covid-19 and transform vaccine development altogether

Vaccines for a sustainable planet

The health of the planet is one objective of the United Nations' Sustainable Development Goals. Vaccines can affect not only human health but also planet health by reducing poverty, preserving microbial diversity, reducing antimicrobial resistance, and preventing an increase in pandemics that is fueled partly by climate change

Novel in vitro booster vaccination to rapidly generate antigen-specific human monoclonal antibodies

Vaccines remain the most effective tool to prevent infectious diseases. Here, we introduce an in vitro booster vaccination approach that relies on antigen-dependent activation of human memory B cells in culture. This stimulation induces antigen-specific B cell proliferation, differentiation of B cells into plasma cells, and robust antibody secretion after a few days of culture. We validated this strategy using cells from healthy donors to retrieve human antibodies against tetanus toxoid and influenza hemagglutinin (HA) from H1N1 and newly emergent subtypes such as H5N1 and H7N9. Anti-HA antibodies were cross-reactive against multiple subtypes, and some showed neutralizing activity. Although these antibodies may have arisen as a result of previous influenza infection, we also obtained gp120-reactive antibodies from non–HIV-infected donors, indicating that we can generate antibodies without prior antigenic exposure. Overall, our novel approach can be used to rapidly produce therapeutic antibodies and has the potential to assess the immunogenicity of candidate antigens, which could be exploited in future vaccine development

A generalized HIV vaccine design strategy for priming of broadly neutralizing antibody responses

Vaccine induction of broadly neutralizing antibodies (bnAbs) to HIV remains a major challenge. Germline-targeting immunogens hold promise for initiating the induction of certain bnAb classes; yet for most bnAbs, a strong dependence on antibody heavy chain complementarity-determining region 3 (HCDR3) is a major barrier. Exploiting ultradeep human antibody sequencing data, we identified a diverse set of potential antibody precursors for a bnAb with dominant HCDR3 contacts. We then developed HIV envelope trimer–based immunogens that primed responses from rare bnAb-precursor B cells in a mouse model and bound a range of potential bnAb-precursor human naïve B cells in ex vivo screens. Our repertoire-guided germline-targeting approach provides a framework for priming the induction of many HIV bnAbs and could be applied to most HCDR3-dominant antibodies from other pathogens

Germline-targeting HIV vaccination induces neutralizing antibodies to the CD4 binding site

Eliciting potent and broadly neutralizing antibodies (bnAbs) is a major goal in HIV-1 vaccine development. Here, we describe how germline-targeting immunogen BG505 SOSIP germline trimer 1.1 (GT1.1), generated through structure-based design, engages a diverse range of VRC01-class bnAb precursors. A single immunization with GT1.1 expands CD4 binding site (CD4bs)–specific VRC01-class B cells in knock-in mice and drives VRC01-class maturation. In nonhuman primates (NHPs), GT1.1 primes CD4bs-specific neutralizing serum responses. Selected monoclonal antibodies (mAbs) isolated from GT1.1-immunized NHPs neutralize fully glycosylated BG505 virus. Two mAbs, 12C11 and 21N13, neutralize subsets of diverse heterologous neutralization-resistant viruses. High-resolution structures revealed that 21N13 targets the same conserved residues in the CD4bs as VRC01-class and CH235-class bnAbs despite its low sequence similarity (~40%), whereas mAb 12C11 binds predominantly through its heavy chain complementarity-determining regio