BCG vaccination induces cross-protective immunity against pathogenic microorganisms.

Bacillus Calmette-Guérin (BCG) is an attenuated Mycobacterium bovis strain used as a vaccine to prevent Mycobacterium tuberculosis (M. tb) infection. Its ability to potentiate the immune response induced by other vaccines and to promote nonspecific immunomodulatory effects has been described. These effects can be triggered by epigenetic reprogramming and metabolic shifts on innate immune cells, a phenomenon known as trained immunity. The induction of trained immunity may contribute to explain why BCG vaccination effectively decreases disease symptoms caused by pathogens different from M. tb. This article explains the importance of BCG immunization and the possible mechanisms associated with the induction of trained immunity, which might be used as a strategy for rapid activation of the immune system against unrelated pathogens.

Persistent organic pollutants and cognitive decline among middle-aged or older adults in the Hispanic Community Health Study/Study of Latinos.

Persistent organic pollutants may negatively impact cognition; however, associations between persistent organic pollutants and changes in cognition among United States Hispanic/Latino adults have not been investigated. Herein, we examined the associations between 33 persistent organic pollutants and cognitive changes among 1837 Hispanic/Latino adults. At baseline (2008-2011; Visit 1), participants provided biospecimens in which we measured levels of 5 persistent pesticides or pesticide metabolites, 4 polybrominated diphenyl ethers and 2,2',4,4',5,5'-hexabromobiphenyl, and 24 polychlorinated biphenyls. At Visit 1 and again at Visit 2 (2015-2018), a battery of neurocognitive tests was administered which included the Brief-Spanish English Verbal Learning Test, Word Fluency Test, and Digit Symbol Substitution Test. To estimate the adjusted associations between changes in cognition and each POP, we used linear regression for survey data. Each doubling in plasma levels of polychlorinated biphenyls 146, 178, 194, 199/206, and 209 was associated with steeper declines in global cognition (ßs range:-0.053 to -0.061) with stronger associations for the Brief-Spanish English Verbal Learning Test. Persistent organic pollutants, in particular polychlorinated biphenyls, were associated with declines in cognition over 7 years and may be a concern for Hispanic/Latino adults.

Remediation of Thirdhand Tobacco Smoke with Ozone: Probing Deep Reservoirs in Carpets.

We assessed the efficacy of ozonation as an indoor remediation strategy by evaluating how a carpet serves as a sink and long-term source of thirdhand tobacco smoke (THS) while protecting contaminants absorbed in deep reservoirs by scavenging ozone. Specimens from unused carpet that was exposed to smoke in the lab ("fresh THS") and contaminated carpets retrieved from smokers' homes ("aged THS") were treated with 1000 ppb ozone in bench-scale tests. Nicotine was partially removed from fresh THS specimens by volatilization and oxidation, but it was not significantly eliminated from aged THS samples. By contrast, most of the 24 polycyclic aromatic hydrocarbons detected in both samples were partially removed by ozone. One of the home-aged carpets was installed in an 18 m3 room-sized chamber, where its nicotine emission rate was 950 ng day-1 m-2. In a typical home, such daily emissions could amount to a non-negligible fraction of the nicotine released by smoking one cigarette. The operation of a commercial ozone generator for a total duration of 156 min, reaching concentrations up to 10,000 ppb, did not significantly reduce the carpet nicotine loading (26-122 mg m-2). Ozone reacted primarily with carpet fibers, rather than with THS, leading to short-term emissions of aldehydes and aerosol particles. Hence, by being absorbed deeply into carpet fibers, THS constituents can be partially shielded from ozonation.

Policy-relevant differences between secondhand and thirdhand smoke: strengthening protections from involuntary exposure to tobacco smoke pollutants.

Starting in the 1970s, individuals, businesses and the public have increasingly benefited from policies prohibiting smoking indoors, saving thousands of lives and billions of dollars in healthcare expenditures. Smokefree policies to protect against secondhand smoke exposure, however, do not fully protect the public from the persistent and toxic chemical residues from tobacco smoke (also known as thirdhand smoke) that linger in indoor environments for years after smoking stops. Nor do these policies address the economic costs that individuals, businesses and the public bear in their attempts to remediate this toxic residue. We discuss policy-relevant differences between secondhand smoke and thirdhand smoke exposure: persistent pollutant reservoirs, pollutant transport, routes of exposure, the time gap between initial cause and effect, and remediation and disposal. We examine four policy considerations to better protect the public from involuntary exposure to tobacco smoke pollutants from all sources. We call for (a) redefining smokefree as free of tobacco smoke pollutants from secondhand and thirdhand smoke; (b) eliminating exemptions to comprehensive smoking bans; (c) identifying indoor environments with significant thirdhand smoke reservoirs; and (d) remediating thirdhand smoke. We use the case of California as an example of how secondhand smoke-protective laws may be strengthened to encompass thirdhand smoke protections. The health risks and economic costs of thirdhand smoke require that smokefree policies, environmental protections, real estate and rental disclosure policies, tenant protections, and consumer protection laws be strengthened to ensure that the public is fully protected from and informed about the risks of thirdhand smoke exposure.

Type I Natural Killer T Cells as Key Regulators of the Immune Response to Infectious Diseases.

The immune system must work in an orchestrated way to achieve an optimal response upon detection of antigens. The cells comprising the immune response are traditionally divided into two major subsets, innate and adaptive, with particular characteristics for each type. Type I natural killer T (iNKT) cells are defined as innate-like T cells sharing features with both traditional adaptive and innate cells, such as the expression of an invariant T cell receptor (TCR) and several NK receptors. The invariant TCR in iNKT cells interacts with CD1d, a major histocompatibility complex class I (MHC-I)-like molecule. CD1d can bind and present antigens of lipid nature and induce the activation of iNKT cells, leading to the secretion of various cytokines, such as gamma interferon (IFN-γ) and interleukin 4 (IL-4). These cytokines will aid in the activation of other immune cells following stimulation of iNKT cells. Several molecules with the capacity to bind to CD1d have been discovered, including α-galactosylceramide. Likewise, several molecules have been synthesized that are capable of polarizing iNKT cells into different profiles, either pro- or anti-inflammatory. This versatility allows NKT cells to either aid or impair the clearance of pathogens or to even control or increase the symptoms associated with pathogenic infections. Such diverse contributions of NKT cells to infectious diseases are supported by several publications showing either a beneficial or detrimental role of these cells during diseases. In this article, we discuss current data relative to iNKT cells and their features, with an emphasis on their driving role in diseases produced by pathogenic agents in an organ-oriented fashion.

Safety and Immunogenicity of an Inactivated Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine in a Subgroup of Healthy Adults in Chile.

BACKGROUND: The development of effective vaccines against coronavirus disease 2019 is a global priority. CoronaVac is an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine with promising safety and immunogenicity profiles. This article reports safety and immunogenicity results obtained for healthy Chilean adults aged ≥18 years in a phase 3 clinical trial. METHODS: Volunteers randomly received 2 doses of CoronaVac or placebo, separated by 2 weeks. A total of 434 volunteers were enrolled, 397 aged 18-59 years and 37 aged ≥60 years. Solicited and unsolicited adverse reactions were registered from all volunteers. Blood samples were obtained from a subset of volunteers and analyzed for humoral and cellular measures of immunogenicity. RESULTS: The primary adverse reaction in the 434 volunteers was pain at the injection site, with a higher incidence in the vaccine than in the placebo arm. Adverse reactions observed were mostly mild and local. No severe adverse events were reported. The humoral evaluation was performed on 81 volunteers. Seroconversion rates for specific anti-S1-receptor binding domain (RBD) immunoglobulin G (IgG) were 82.22% and 84.44% in the 18-59 year age group and 62.69% and 70.37% in the ≥60 year age group, 2 and 4 weeks after the second dose, respectively. A significant increase in circulating neutralizing antibodies was detected 2 and 4 weeks after the second dose. The cellular evaluation was performed on 47 volunteers. We detected a significant induction of T-cell responses characterized by the secretion of interferon-γ (IFN-γ) upon stimulation with Mega Pools of peptides from SARS-CoV-2. CONCLUSIONS: Immunization with CoronaVac in a 0-14 schedule in Chilean adults aged ≥18 years is safe, induces anti-S1-RBD IgG with neutralizing capacity, activates T cells, and promotes the secretion of IFN-γ upon stimulation with SARS-CoV-2 antigens.

Nicotine, Cotinine, and Tobacco-Specific Nitrosamines Measured in Children's Silicone Wristbands in Relation to Secondhand Smoke and E-cigarette Vapor Exposure.

INTRODUCTION: Simple silicone wristbands (WB) hold promise for exposure assessment in children. We previously reported strong correlations between nicotine in WB worn by children and urinary cotinine (UC). Here, we investigated differences in WB chemical concentrations among children exposed to secondhand smoke from conventional cigarettes (CC) or secondhand vapor from electronic cigarettes (EC), and children living with nonusers of either product (NS). METHODS: Children (n = 53) wore three WB and a passive nicotine air sampler for 7 days and one WB for 2 days, and gave a urine sample on day 7. Caregivers reported daily exposures during the 7-day period. We determined nicotine, cotinine, and tobacco-specific nitrosamines (TSNAs) concentrations in WB, nicotine in air samplers, and UC through isotope-dilution liquid chromatography with triple-quadrupole mass spectrometry. RESULTS: Nicotine and cotinine levels in WB in children differentiated between groups of children recruited into NS, EC exposed, and CC exposed groups in a similar manner to UC. WB levels were significantly higher in the CC group (WB nicotine median 233.8 ng/g silicone, UC median 3.6 ng/mL, n = 15) than the EC group (WB nicotine median: 28.9 ng/g, UC 0.5 ng/mL, n = 19), and both CC and EC group levels were higher than the NS group (WB nicotine median: 3.7 ng/g, UC 0.1 ng/mL, n = 19). TSNAs, including the known carcinogen NNK, were detected in 39% of WB. CONCLUSIONS: Silicone WB show promise for sensitive detection of exposure to tobacco-related contaminants from traditional and electronic cigarettes and have potential for tobacco control efforts. IMPLICATIONS: Silicone WB worn by children can absorb nicotine, cotinine, and tobacco-specific nitrosamines, and amounts of these compounds are closely related to the child's urinary cotinine. Levels of tobacco-specific compounds in the silicone WB can distinguish patterns of children's exposure to secondhand smoke and e-cigarette vapor. Silicone WB are simple to use and acceptable to children and, therefore, may be useful for tobacco control activities such as parental awareness and behavior change, and effects of smoke-free policy implementation.

Longitudinal assessment of kidney function in migrant farm workers.

Chronic kidney disease of unknown etiology (CKDu) is an epidemic that affects young agricultural workers in several warm regions of the world. However, there is a lack of monitoring of kidney issues in regions with extremely warm environments such as the Northwest of Mexico, a semi-arid region with a growing agricultural industry, where migrant and seasonal farm workers (MSFWs) travel to work in the fields. The objective of this study was to longitudinally assess kidney functioning of MSFWs in relation to pesticide exposure, heat stress and dehydration in a large-scale farm in Mexico. We enrolled 101 MSFWs, of whom 50 were randomly selected to work in an organic certified area and 51 were randomly selected to work in a conventional area. We also enrolled 50 office workers within the same region as a reference group. We collected urine and blood samples from all workers in addition to demographic, behavioral, and occupational characteristics. The physiological strain index (PSI) was used to estimate workers' heat strain. Sampling was conducted at pre-harvest (March) and late in the harvest (July). Linear mixed models were built with the estimated glomerular filtration rate (eGFR) as the dependent variable. We found a significant decrease in kidney function in MSFWs compared to office workers. By the late harvest, one MSFW developed kidney disease, two MSFWs suffered a kidney injury, and 14 MSFWs were at risk of a kidney injury. We found that the eGFR in MSFWs decreased significantly from pre-harvest (125 ± 13.0 mL/min/1.73 m2) to late harvest (109 ± 13.6 mL/min/1.73 m2) (p < 0.001), while no significant change was observed in office workers. The eGFR was significantly lower in MSFWs who worked in the conventional field (101.2 ± 19.4 mL/min/1.73 m2) vs the organic field (110.9 ± 13.6 mL/min/1.73 m2) (p = 0.002). In our final model, we found that dehydration was associated with the decrease of eGFR. We also found an interaction between heat strain and job category, as a significant decline in eGFR by job category (conventional/organic MSFWs and office workers) was related to an increase in heat strain. This suggests that pesticide exposure needs to be considered in combination with heat stress and dehydration. This study provides valuable information on kidney function in MSFWs, and it shows the importance of early long-term monitoring in farm workers in other regions where CKDu has not been evaluated yet.

Antibody development for preventing the human respiratory syncytial virus pathology.

Human respiratory syncytial virus (hRSV) is the most important etiological agent causing hospitalizations associated with respiratory diseases in children under 5 years of age as well as the elderly, newborns and premature children are the most affected populations. This viral infection can be associated with various symptoms, such as fever, coughing, wheezing, and even pneumonia and bronchiolitis. Due to its severe symptoms, the need for mechanical ventilation is not uncommon in clinical practice. Additionally, alterations in the central nervous system -such as seizures, encephalopathy and encephalitis- have been associated with cases of hRSV-infections. Furthermore, the absence of effective vaccines or therapies against hRSV leads to elevated expenditures by the public health system and increased mortality rates for the high-risk population. Along these lines, vaccines and therapies can elicit different responses to this virus. While hRSV vaccine candidates seek to promote an active immune response associated with the achievement of immunological memory, other therapies -such as the administration of antibodies- provide a protective environment, although they do not trigger the activation of the immune system and therefore do not promote an immunological memory. An interesting approach to vaccination is the use of virus-neutralizing antibodies, which inhibit the entry of the pathogen into the host cells, therefore impairing the capacity of the virus to replicate. Currently, the most common molecule targeted for antibody design against hRSV is the F protein of this virus. However, other molecular components of the virus -such as the G or the N hRSV proteins- have also been explored as potential targets for the control of this disease. Currently, palivizumab is the only monoclonal antibody approved for human use. However, studies in humans have shown a protective effect only after the administration of at least 3 to 5 doses, due to the stability of this vaccine. Furthermore, other studies suggest that palivizumab only has an effectiveness close to 50% in high-risk infants. In this work, we will review different strategies addressed for the use of antibodies in a prophylactic or therapeutic context and their ability to prevent the symptoms caused by hRSV infection of the airways, as well as in other tissues such as the CNS.

New Insights Contributing to the Development of Effective Vaccines and Therapies to Reduce the Pathology Caused by hRSV.

Human Respiratory Syncytial Virus (hRSV) is one of the major causes of acute lower respiratory tract infections (ALRTI) worldwide, leading to significant levels of immunocompromisation as well as morbidity and mortality in infants. Its main target of infection is the ciliated epithelium of the lungs and the host immune responses elicited is ineffective at achieving viral clearance. It is thought that the lack of effective immunity against hRSV is due in part to the activity of several viral proteins that modulate the host immune response, enhancing a Th2-like pro-inflammatory state, with the secretion of cytokines that promote the infiltration of immune cells to the lungs, with consequent damage. Furthermore, the adaptive immunity triggered by hRSV infection is characterized by weak cytotoxic T cell responses and secretion of low affinity antibodies by B cells. These features of hRSV infection have meant that, to date, no effective and safe vaccines have been licensed. In this article, we will review in detail the information regarding hRSV characteristics, pathology, and host immune response, along with several prophylactic treatments and vaccine prototypes. We will also expose significant data regarding the newly developed BCG-based vaccine that promotes protective cellular and humoral response against hRSV infection, which is currently undergoing clinical evaluation.

New insights on the viral and host factors contributing to the airway pathogenesis caused by the respiratory syncytial virus.

The respiratory syncytial virus (RSV) is the most prevalent etiological agent of lower respiratory tract infections and the first cause of hospitalization in infants due to respiratory disease worldwide. However, efforts to develop safe and effective vaccines and antivirals have been challenged by an incomplete understanding of the RSV pathogenesis and the host immune response to RSV infection in the airways. Here, we discuss recent advances in understanding the interaction between RSV and the epithelium to induce pathogenesis in the airways, such as the role of the RSV NS2 protein in the airway epithelium, as well as the events involved in the RSV entry process. In addition, we summarize the cellular factors produced by airway epithelial cells (AECs) in response to RSV infection that lead to the activation of innate and adaptive immune responses, inducing lung inflammation and disease. Further, we discuss the possible contribution of a recently identified cytokine, thymic stromal lymphopoitein (TSLP), in the lung immunopathology caused by RSV.

QuickFit: A High-Throughput RT-qPCR-Based Assay to Quantify Viral Growth and Fitness In Vitro.

Quantifying viral growth rates is key to understanding evolutionary dynamics and the potential for mutants to escape antiviral drugs. Defining evolutionary escape paths and their impact on viral fitness allows for the development of drugs that are resistant to escape. In the case of HIV, combination antiretroviral therapy can successfully prevent or treat infection, but it relies on strict adherence to prevent escape. Here, we present a method termed QuickFit that enables the quantification of viral fitness by employing large numbers of parallel viral cultures to measure growth rates accurately. QuickFit consistently recapitulated HIV growth measurements obtained by traditional approaches, but with significantly higher throughput and lower rates of error. This method represents a promising tool for rapid and consistent evaluation of viral fitness.

Novel chemical contaminants associated with thirdhand smoke in settled house dust.

Thirdhand smoke (THS) is the persistent and toxic residue from tobacco smoke in indoor environments. A comprehensive understanding of the chemical constituents of THS is necessary to assess the risks of long-term exposure and to establish reliable THS tracers. The objective of this study was to investigate compounds associated with THS through nontargeted analysis (NTA) of settled house dust samples from smokers' and non-smokers' homes, using comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC×GC/TOF-MS). Compounds that were either only present in dust from smokers' homes or that had significantly larger abundance than in non-smokers' homes were termed qualified compounds. We identified 140 qualified compounds, and of these, 42 compounds were tentatively identified by searching matching mass spectra in NIST electron impact (EI) mass spectral library including 20 compounds confirmed with their authentic standards. Among the 42 compounds, 26 compounds were statistically more abundant (p < 0.10) in dust from homes of smokers; seven were tobacco-specific compounds, two of which (nornicotyrine, 3-ethenylpyridine) have not been reported before in house dust. Two compounds, tris (2-chloroethyl) phosphate (a toxic compound used as a flame retardant and reported in tobacco) and propanoic acid, 2-methyl-, 1-(1,1-dimethylethyl)-2-methyl-1,3-propanediyl ester (highly abundant and reported in exhaled air of smokers), were found in dust from all smokers' homes and in zero non-smokers' homes, making these potential THS tracers, possibly associated with recent smoking. Benzyl methyl ketone was significantly higher in dust in smokers' homes, and was previously reported not as a product of tobacco but rather as a form of methamphetamine. This compound was recently reported in mainstream tobacco smoke condensate through NTA as well. These identified potential tracers and chemical components of THS in this study can be further investigated for use in developing THS contamination and exposure assessments.

HIV broadly neutralizing antibody escapability drives the therapeutic efficacy of vectored immunotherapy.

Broadly neutralizing antibodies (bNAbs) have shown great promise for prevention and treatment of HIV infection. Breadth of bNAb neutralization, measured in vitro across panels of diverse viral isolates, is often used as a predictor of clinical potential. However, recent prevention studies demonstrate that the clinical efficacy of a broad and potent bNAb (VRC01) is undermined by neutralization resistance of circulating strains. Using HIV-infected humanized mice, we find that therapeutic efficacy of bNAbs delivered as Vectored ImmunoTherapy (VIT) is a function of both the fitness cost and resistance benefit of mutations that emerge during viral escape, which we term 'escapability'. Applying this mechanistic framework, we find that the sequence of the envelope V5-loop alters the resistance benefits of mutants that arise during escape, thereby impacting the therapeutic efficacy of VIT-mediated viral suppression. We also find that an emtricitabine-based antiretroviral drug regimen dramatically enhances the efficacy of VIT, by reducing the fitness of mutants along the escape path. Our findings demonstrate that bNAb escapability is a key determinant to consider in the rational design of antibody regimens with maximal efficacy and illustrates a tractable means of minimizing viral escape from existing bNAbs.

Contamination of surfaces in children's homes with nicotine and the potent carcinogenic tobacco-specific nitrosamine NNK.

BACKGROUND: Tobacco smoke exposure (TSE) through secondhand and thirdhand smoke is a modifiable risk factor that contributes to childhood morbidity. Limited research has assessed surface TSE pollution in children's environments as a potential source of thirdhand smoke exposure, and none have examined levels of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) on surfaces. OBJECTIVE: This study measured surface NNK and nicotine in children's homes and associations with sociodemographics and parent-reported TSE behaviors. We assessed correlations of surface NNK and nicotine with dust NNK, dust nicotine, and child cotinine. METHODS: Home surface wipe NNK and nicotine data from 84 children who lived with smokers were analyzed. Tobit and simple linear regression analyses were conducted to assess associations of surface NNK and nicotine with child characteristics. Spearman's (ρ) correlations assessed the strength of associations between environmental markers and child cotinine. RESULTS: Nearly half (48.8%) of children's home surfaces had detectable NNK and 100% had detectable nicotine. The respective geometric means (GMs) of surface NNK and nicotine loadings were 14.0 ng/m2 and 16.4 µg/m2. Surface NNK positively correlated with surface nicotine (ρ = 0.54, p < 0.001) and dust NNK (ρ = 0.30, p = 0.020). Surface nicotine positively correlated with dust NNK (ρ = 0.42, p < 0.001) and dust nicotine (ρ = 0.24, p = 0.041). Children with household incomes ≤$15,000 had higher surface NNK levels (GM = 18.7 ng/m2, p = 0.017) compared to children with household incomes >$15,000 (GM = 7.1 ng/m2). Children with no home smoking bans had higher surface NNK (GM = 18.1 ng/m2, p = 0.020) and surface nicotine (GM = 17.7 µg/m2, p = 0.019) levels compared to children with smoking bans (GM = 7.5 ng/m2, 4.8 µg/m2, respectively). IMPACT: Although nicotine on surfaces is an established marker of thirdhand smoke pollution, other thirdhand smoke contaminants have not been measured on surfaces in the homes of children living with smokers. We provide evidence that the potent carcinogenic tobacco-specific nitrosamine NNK was detectable on surfaces in nearly half of children's homes, and nicotine was detectable on all surfaces. Surface NNK was positively correlated with surface nicotine and dust NNK. Detectable surface NNK levels were found in homes with indoor smoking bans, indicating the role of NNK as a persistent thirdhand smoke pollutant accumulating on surfaces as well as in dust.

Environmental and structural factors associated with bacterial diversity in household dust across the Arizona-Sonora border.

We previously reported that asthma prevalence was higher in the United States (US) compared to Mexico (MX) (25.8% vs. 8.4%). This investigation assessed differences in microbial dust composition in relation to demographic and housing characteristics on both sides of the US-MX Border. Forty homes were recruited in the US and MX. Home visits collected floor dust and documented occupants' demographics, asthma prevalence, housing structure, and use characteristics. US households were more likely to have inhabitants who reported asthma when compared with MX households (30% vs. 5%) and had significantly different flooring types. The percentage of households on paved roads, with flushing toilets, with piped water and with air conditioning was higher in the US, while dust load was higher in MX. Significant differences exist between countries in the microbial composition of the floor dust. Dust from Mexican homes was enriched with Alishewanella, Paracoccus, Rheinheimera genera and Intrasporangiaceae family. A predictive metagenomics analysis identified 68 significantly differentially abundant functional pathways between US and MX. This study documented multiple structural, environmental, and demographic differences between homes in the US and MX that may contribute to significantly different microbial composition of dust observed in these two countries.

Delivery platforms for broadly neutralizing antibodies.

PURPOSE OF REVIEW: Passive administration of broadly neutralizing antibodies (bNAbs) is being evaluated as a therapeutic approach to prevent or treat HIV infections. However, a number of challenges face the widespread implementation of passive transfer for HIV. To reduce the need of recurrent administrations of bNAbs, gene-based delivery approaches have been developed which overcome the limitations of passive transfer. RECENT FINDINGS: The use of DNA and mRNA for the delivery of bNAbs has made significant progress. DNA-encoded monoclonal antibodies (DMAbs) have shown great promise in animal models of disease and the underlying DNA-based technology is now being tested in vaccine trials for a variety of indications. The COVID-19 pandemic greatly accelerated the development of mRNA-based technology to induce protective immunity. These advances are now being successfully applied to the delivery of monoclonal antibodies using mRNA in animal models. Delivery of bNAbs using viral vectors, primarily adeno-associated virus (AAV), has shown great promise in preclinical animal models and more recently in human studies. Most recently, advances in genome editing techniques have led to engineering of monoclonal antibody expression from B cells. These efforts aim to turn B cells into a source of evolving antibodies that can improve through repeated exposure to the respective antigen. SUMMARY: The use of these different platforms for antibody delivery has been demonstrated across a wide range of animal models and disease indications, including HIV. Although each approach has unique strengths and weaknesses, additional advances in efficiency of gene delivery and reduced immunogenicity will be necessary to drive widespread implementation of these technologies. Considering the mounting clinical evidence of the potential of bNAbs for HIV treatment and prevention, overcoming the remaining technical challenges for gene-based bNAb delivery represents a relatively straightforward path towards practical interventions against HIV infection.

Changes and stability of hand nicotine levels in children of smokers: Associations with urinary biomarkers, reported child tobacco smoke exposure, and home smoking bans.

BACKGROUND: Exposure to thirdhand smoke (THS) residue takes place through inhalation, ingestion, and dermal transfer. Hand nicotine levels have been proposed to measure THS pollution in the environment of children, but little is known about its variability and stability over time and correlates of change. OBJECTIVES: The goal was to determine the stability of hand nicotine in comparison to urinary biomarkers and to explore factors that influence changes in hand nicotine. METHODS: Data were collected from 0 to 11-year-old children (Mean age = 5.9) who lived with ≥1 tobacco smokers (N = 129). At a 6-week interval, we collected repeated measures of hand nicotine, four urinary biomarkers (cotinine, trans-3'-hydroxycotinine, nicotelline N-oxides, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol), and parent-reported child tobacco smoke exposure (TSE). Dependent sample t-tests, correlations, and multivariable regression analyses were conducted to examine the changes in child TSE. RESULTS: Hand nicotine levels (r = 0.63, p < 0.001) showed similar correlations between repeated measures to urinary biomarkers (r = 0.58-0.71; p < 0.001). Different from urinary biomarkers, mean hand nicotine levels increased over time (t(113) = 3.37, p < 0.001) being significantly higher in children from homes without smoking bans at Time 2 (p = 0.016) compared to Time 1 (p = 0.003). Changes in hand nicotine correlated with changes in cotinine and trans-3'-hydroxycotinine (r = 0.30 and r = 0.19, respectively, p < 0.05). Children with home smoking bans at Time 1 and 2 showed significantly lower hand nicotine levels compared to children without home smoking bans. DISCUSSION: Findings indicate that hand nicotine levels provide additional insights into children's exposure to tobacco smoke pollutants than reported child TSE and urinary biomarkers. Changes in hand nicotine levels show that consistent home smoking bans in homes of children of smokers can lower THS exposure. Hand nicotine levels may be influenced by the environmental settings in which they are collected.

Characterization of the humoral and cellular immunity induced by a recombinant BCG vaccine for the respiratory syncytial virus in healthy adults.

Introduction: The human respiratory syncytial virus (hRSV) is responsible for most respiratory tract infections in infants. Even though currently there are no approved hRSV vaccines for newborns or infants, several candidates are being developed. rBCG-N-hRSV is a vaccine candidate previously shown to be safe in a phase I clinical trial in adults (clinicaltrials.gov identifier #NCT03213405). Here, secondary immunogenicity analyses were performed on these samples. Methods: PBMCs isolated from immunized volunteers were stimulated with hRSV or mycobacterial antigens to evaluate cytokines and cytotoxic T cell-derived molecules and the expansion of memory T cell subsets. Complement C1q binding and IgG subclass composition of serum antibodies were assessed. Results: Compared to levels detected prior to vaccination, perforin-, granzyme B-, and IFN-γ-producing PBMCs responding to stimulus increased after immunization, along with their effector memory response. N-hRSV- and mycobacterial-specific antibodies from rBCG-N-hRSV-immunized subjects bound C1q. Conclusion: Immunization with rBCG-N-hRSV induces cellular and humoral immune responses, supporting that rBCG-N-hRSV is immunogenic and safe in healthy individuals. Clinical trial registration: https://classic.clinicaltrials.gov/ct2/show/, identifier NCT03213405.

Environmental and Structural Factors Associated with Bacterial Diversity in Household Dust Across the Arizona-Sonora Border.

We previously reported that asthma prevalence was higher in the United States (US) compared to Mexico (MX) (25.8% vs 8.4%). This investigation assessed differences in microbial dust composition in relation to demographic and housing characteristics on both sides of the US-MX Border. Forty homes were recruited in the US and MX. Home visits collected floor dust and documented occupants' demographics, asthma prevalence, and housing structure and use characteristics. US households were more likely to have inhabitants who reported asthma when compared with MX households (30% vs 5%) and had significantly different flooring types. The percentage of households on paved roads, with flushing toilets, with piped water and with air conditioning was higher in the US, while dust load was higher in MX. Significant differences exist between countries in the microbial composition of the floor dust. Dust from US homes was enriched with Geodermatophilus, whereas dust from Mexican homes was enriched with Alishewanella and Chryseomicrobium. A predictive metagenomics analysis identified 68 significantly differentially abundant functional pathways between US and MX. This study documented multiple structural, environmental, and demographic differences between homes in the US and MX that may contribute to significantly different microbial composition of dust observed in these two countries.