Salivary polyreactive antibodies and Haemophilus influenzae are associated with respiratory infection severity in young children with recurrent respiratory infections.

BACKGROUND: Recurrent respiratory tract infections (rRTIs) are a common reason for immunodiagnostic testing in children, which relies on serum antibody level measurements. However, because RTIs predominantly affect the respiratory mucosa, serum antibodies may inaccurately reflect local immune defences. We investigated antibody responses in saliva and their interplay with the respiratory microbiota in relation to RTI severity and burden in young children with rRTIs. METHODS: We conducted a prospective cohort study including 100 children aged <10 years with rRTIs, their family members, and healthy healthcare professionals. Total and polyreactive antibody concentrations were determined in serum and saliva (ELISA); respiratory microbiota composition (16S-rRNA-sequencing) and respiratory viruses (qPCR) were characterised in nasopharyngeal swabs. Proteomic analysis (Olink®) was performed on saliva and serum samples. RTI symptoms were monitored with a daily cell phone application and assessed using latent class analysis and negative binomial mixed models. RESULTS: Serum antibody levels were not associated with RTI severity. Strikingly, 28% of salivary antibodies and only 2% of serum antibodies displayed polyreactivity (p<0.001). Salivary polyreactive immunoglobulin A (IgA) was negatively associated with recurrent lower RTIs (aOR 0.80 [95% CI 0.67-0.94]) and detection of multiple respiratory viruses (aOR 0.76 [95% CI 0.61-0.96]). Haemophilus influenzae abundance was positively associated with RTI symptom burden (regression coefficient 0.07 [95% CI 0.02-0.12]). CONCLUSION: These results highlight the importance of mucosal immunity in RTI severity and burden and suggest that the level of salivary polyreactive IgA and H. influenzae abundance may serve as indicators of infection risk and severity in young children with rRTIs.

Cardiovascular events after invasive pneumococcal disease: a retrospective cohort study.

OBJECTIVES: This study aims to understand the magnitude of and mechanisms underlying the development of cardiovascular events (CVEs) in patients with invasive pneumococcal disease (IPD). We aimed to identify factors that contribute to the occurrence of CVEs within 1 year after admission and discuss implications for patient care. METHODS: A multicentered cohort study included adult patients from four Dutch hospitals who had a positive blood culture for Streptococcus pneumoniae and any type of clinical manifestation between 2012 and 2020. Disease characteristics and microbiological data were systematically collected from electronic patient files. The main outcome measures were the occurrence of stroke and acute coronary syndromes (ACS). RESULTS: Of 914 eligible patients, 4.2% experienced a CVE within 1 year after admission for IPD. ACS mainly occurred in the first 2 weeks, whereas stroke developed throughout follow-up. Although ACS was positively associated with disease severity, the sole independent predictor was alcohol abuse (odds ratio [OR] 3.840, 95% confidence interval [CI] 1.108-13.303). Although stroke occurred in 6.3% of meningitis cases, the best clinical predictor of stroke was a body temperature >39.5 °C at admission (OR 3.117 [1.154-8.423]). In the adult IPD population aged <70 years, pneumococcal serotypes were the primary predictors of ACS (7F; OR 15.733 [1.812-136.632]) and stroke (22F; OR 7.320 [1.193-44.903]). CONCLUSIONS: Adverse CVEs were not uncommon after IPD diagnosis and deserve attention, especially in the high-risk groups we identified in our study population. Whether specific serotypes play a role in the development of CVE requires substantiation in further research.

Determinants of Systemic SARS-CoV-2-Specific Antibody Responses to Infection and to Vaccination: A Secondary Analysis of Randomised Controlled Trial Data.

SARS-CoV-2 infections elicit antibodies against the viral spike (S) and nucleocapsid (N) proteins; COVID-19 vaccines against the S-protein only. The BCG-Corona trial, initiated in March 2020 in SARS-CoV-2-naïve Dutch healthcare workers, captured several epidemic peaks and the introduction of COVID-19 vaccines during the one-year follow-up. We assessed determinants of systemic anti-S1 and anti-N immunoglobulin type G (IgG) responses using trial data. Participants were randomised to BCG or placebo vaccination, reported daily symptoms, SARS-CoV-2 test results, and COVID-19 vaccinations, and donated blood for SARS-CoV-2 serology at two time points. In the 970 participants, anti-S1 geometric mean antibody concentrations (GMCs) were much higher than anti-N GMCs. Anti-S1 GMCs significantly increased with increasing number of immune events (SARS-CoV-2 infection or COVID-19 vaccination): 104.7 international units (IU)/mL, 955.0 IU/mL, and 2290.9 IU/mL for one, two, and three immune events, respectively (p < 0.001). In adjusted multivariable linear regression models, anti-S1 and anti-N log10 concentrations were significantly associated with infection severity, and anti-S1 log10 concentration with COVID-19 vaccine type/dose. In univariable models, anti-N log10 concentration was also significantly associated with acute infection duration, and severity and duration of individual symptoms. Antibody concentrations were not associated with long COVID or long-term loss of smell/taste.

Antiviral responses induced by Tdap-IPV vaccination are associated with persistent humoral immunity to Bordetella pertussis.

Many countries continue to experience pertussis epidemics despite widespread vaccination. Waning protection after booster vaccination has highlighted the need for a better understanding of the immunological factors that promote durable protection. Here we apply systems vaccinology to investigate antibody responses in adolescents in the Netherlands (N = 14; NL) and the United Kingdom (N = 12; UK) receiving a tetanus-diphtheria-acellular pertussis-inactivated poliovirus (Tdap-IPV) vaccine. We report that early antiviral and interferon gene expression signatures in blood correlate to persistence of pertussis-specific antibody responses. Single-cell analyses of the innate response identified monocytes and myeloid dendritic cells (MoDC) as principal responders that upregulate antiviral gene expression and type-I interferon cytokine production. With public data, we show that Tdap vaccination stimulates significantly lower antiviral/type-I interferon responses than Tdap-IPV, suggesting that IPV may promote antiviral gene expression. Subsequent in vitro stimulation experiments demonstrate TLR-dependent, IPV-specific activation of the pro-inflammatory p38 MAP kinase pathway in MoDCs. Together, our data provide insights into the molecular host response to pertussis booster vaccination and demonstrate that IPV enhances innate immune activity associated with persistent, pertussis-specific antibody responses.

Survival of Environment-Derived Opportunistic Bacterial Pathogens to Martian Conditions: Is There a Concern for Human Missions to Mars?

The health of astronauts during space travel to new celestial bodies in the Solar System is a critical factor in the planning of a mission. Despite cleaning and decontamination protocols, microorganisms from the Earth have been and will be identified on spacecraft. This raises concerns for human safety and planetary protection, especially if these microorganisms can evolve and adapt to the new environment. In this study, we examined the tolerance of clinically relevant nonfastidious bacterial species that originate from environmental sources (Burkholderia cepacia, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Serratia marcescens) to simulated martian conditions. Our research showed changes in growth and survival of these species in the presence of perchlorates, under desiccating conditions, exposure to ultraviolet radiation, and exposure to martian atmospheric composition and pressure. In addition, our results demonstrate that growth was enhanced by the addition of a martian regolith simulant to the growth media. Additional future research is warranted to examine potential changes in the infectivity, pathogenicity, and virulence of these species with exposure to martian conditions.

Effect of age and season on respiratory mucosal immune marker profiles.

BACKGROUND: The upper respiratory tract is continuously exposed to microorganisms and noxious elements, leading to local immune responses and the secretion of immune markers. While several studies describe immune marker profiles in respiratory mucosal samples in defined patient cohorts, mucosal immune profiles from the general population during the different seasons are lacking. Such baseline profiles are essential to understand the effect of various exposures to the mucosal immune system throughout life. OBJECTIVE: We sought to establish baseline local upper respiratory mucosal immune profiles in the general population and assess these profiles with regard to age, sex, seasonality, and basic health and lifestyle factors. METHODS: We measured the concentrations of 35 immune markers involved in a broad range of immunological processes at the mucosa in nasopharyngeal swab samples from 951 individuals, aged 0 to 86 years, from a nationwide study. RESULTS: Clustering analysis showed that immune marker profiles clearly reflected immunological functions, such as tissue regeneration and antiviral responses. Immune marker concentrations changed strongly with seasonality and age, with the most profound changes occurring in the first 25 years of life; they were also associated with sex, body mass index, smoking, mild symptoms of airway infection, and chronic asthma and hay fever. CONCLUSION: Immunological analyses of noninvasive mucosal samples provide insight into mucosal immune responses to microbial and noxious element exposure in the general population. These data provide a baseline for future studies on respiratory mucosal immune responses and for the development of mucosal immune-based diagnostics.