Judith Helene Aberle

Background: Respiratory syncytial virus (RSV) circulates as two antigenically distinct subgroups, RSV-A and RSV-B, frequently alternating in seasonal predominance. Whether RSV subgroup predominance affects neutralizing immunity and how population immunity shapes subsequent subgroup dynamics, remains unclear. We analyzed multi-season RSV surveillance data and subgroup neutralizing antibody responses to characterize RSV-A/B neutralizing immunity across age groups and successive seasons. Methods: We analyzed 41,899 respiratory samples collected through sentinel surveillance to characterize RSV-A and RSV-B circulation across five seasons (2021–2026). Subgroup neutralization was measured by live-virus neutralization assays in post-season serum samples from infants, children and adults. Results: RSV-A and RSV-B alternated in seasonal predominance, with RSV-A predominating in 2021/22 and 2023/24, RSV-B in 2022/23 and 2025/26, with no clear predominance in 2024/25. In infants, the relative neutralizing activity against RSV-A and RSV-B differed across seasons, whereas adults maintained a balanced neutralizing activity against both subgroups. During the first three years of life, repeated exposure broadened antibody responses toward balanced subgroup neutralization. In the 2021/22, 2022/23, and 2024/25 seasons, lower neutralizing activity in infants was observed against the subgroup that predominated in the subsequent RSV epidemic. Conclusions: Our findings indicate that neutralizing immunity develops from initially subgroup-biased responses after primary RSV infection toward balanced RSV-A/B neutralization with repeated exposure. Subgroup neutralizing activity in infants varied in the context of alternating RSV-A and RSV-B predominance across successive epidemic seasons. These findings provide new insights into age-dependent and seasonally varying patterns of RSV-A/B neutralizing immunity and subgroup circulation.

We previously reported that two of three patients with severe Usutu virus (USUV) disease carried circulating autoantibodies (auto-Abs) neutralizing type I IFNs (AAN-I-IFN). Here, we studied four additional patients, bringing the total number of European patients with life-threatening USUV infection to seven (Austria, n = 1; France, n = 1; Hungary, n = 4; Italy, n = 1). Three of these patients (all male, aged 43, 77, and 78 years, one French and two Hungarian) had blood auto-Abs neutralizing at least 10 ng/ml IFN-α2 and IFN-ω and at least 1 ng/ml IFN-β. They suffered from meningitis (n = 1), meningoencephalitis (n = 1), or myocarditis (n = 1). The other four patients were similar demographically and clinically but had no detectable AAN-I-IFN. No AAN-I-IFN were found in the 63 individuals with silent USUV infection tested (P = 6.4 × 10−4, Fisher’s exact test). These AAN-I-IFN increased the risk of life-threatening USUV disease by 98.8-fold (95% CI: 4.12–2,369; P = 0.0046, Firth’s bias–corrected logistic regression) and, thus, account for almost half the cases of life-threatening USUV infection in Europe.

Mosquito-borne West Nile virus (WNV) infection is a growing global health problem. About 0.5% of infected individuals develop encephalitis. We previously showed that 40% of patients in six cohorts had WNV encephalitis because of circulating autoantibodies (auto-Abs) neutralizing type I IFNs. In seven new cohorts, we found that the prevalence of auto-Abs was highest (40% [17–44%]) in patients with encephalitis and very low in a small sample of individuals with asymptomatic or mild infection. In the 13 European, Middle Eastern, and American cohorts available, odds ratios (OR) for WNV encephalitis in individuals with these auto-Abs relative to those without them in a large sample of the general population untested for WNV infection range from ∼20 (OR = 17.7; 95% CI: 13.8–22.8, P < 10−16) for auto-Abs neutralizing only 100 pg/ml IFN-α2 and/or IFN-ω to >2,000 (OR = 2,218.4; 95% CI: 125.1–39,337.7, P < 10−16) for auto-Abs neutralizing high concentrations of IFN-α2 and high or low concentrations of IFN-ω. Preexisting auto-Abs neutralizing type I IFNs are therefore causal for WNV encephalitis in about 40% of patients.

BACKGROUND: West Nile virus (WNV) and Usutu virus (USUV) outbreaks in Europe pose growing public health concerns. In Austria, human WNV and USUV infections occur nearly every year since 2009 with notable case number variations. AIM: We analysed annual incidences and spatiotemporal distributions of human WNV and USUV infections in Austria in 2009–2024. METHODS: Annual incidence rates of laboratory-confirmed WNV and USUV cases recorded through the national surveillance were calculated, stratified by age, sex, clinical presentation, exposure place and virus sequence. RESULTS: During 2009–2024, recorded case numbers were highest in 2024, with 37 WNV (19 male/18 female; median age: 62 years, range: 18–88) and 27 USUV infections (18 male/9 female; median age: 59 years, range: 20–69). Nineteen WNV cases developed West Nile neuroinvasive disease, while no USUV cases had neurological disease. Thirty-four of the WNV cases and all USUV cases were locally acquired. In northern Burgenland, an eastern Austrian region with an avian hotspot and only sporadic cases previously reported, WNV and USUV incidences respectively rose from averages of 0.6 and 1.0 per 100,000 in previous years to 6.6 and 4.2 per 100,000 in 2024. All 25 sequences analysed in 2024 from locally acquired WNV cases were of lineage 2. Among 15 USUV sequences, 14 belonged to the Europe-2 and one to the Africa-3 clade. CONCLUSION: Human WNV and USUV infection increases in a previously low-incidence region underscore their increasing public health impact in Austria. Strengthening surveillance and response measures is essential for early detection, guiding prevention efforts, and ensuring blood donor safety.

The genus Orthoflavivirus (family Flaviviridae) comprises several important pathogens that are widespread across the globe, often co-circulating in many regions. In Austria, the closely related mosquito-borne West Nile (WN) and Usutu (USU) viruses have been detected since the early 2000s. Orthoflavivirus-neutralizing antibodies primarily target the major envelope protein E. However, due to their antigenic relationship, recurring contacts with different orthoflaviviruses can lead to the induction of broadly cross-reactive E-specific antibodies. These can pose a problem in the diagnosis and differentiation of orthoflavivirus infections. Therefore, we established immunological assays based on the non-structural protein 1 (NS1) to differentiate infections caused by WN and USU viruses. The NS1 protein is secreted during acute infection, and NS1-specific antibodies have been reported to be less cross-reactive than those against E. Using sera from individuals with a confirmed WN or USU virus infection, it was possible to distinguish between the two virus infections with high accuracy, specifically when IgM and IgG results were combined.

Background: Vaccination programmes initiated in the early 1970s reduced the incidence of measles in Austria, which resulted in the interruption of endemic measles virus (MeV) circulation and the achievement of elimination status in 2018. However, large outbreaks occurred in 2023 and 2024. Aim: By assessing MeV-specific IgG antibody levels, we analysed if immunity recently declined due to the COVID-19 pandemic, vaccine-induced immunity waned over long term or immunity gaps already pre-existed in the population. Methods: We determined anti-MeV antibody levels in a retrospective dataset of 56,360 diagnostic samples (from 50,754 individuals) collected 2010–2024 and correlated antibody cutoffs to titres from a live-virus neutralisation test. Results: Individuals born before 1970 (n = 15,007) had antibody levels > 3,000 IU/L, persisting into higher age, and < 2% (n = 300) of them were seronegative. In contrast, individuals born after 1990 (n = 12,778) displayed seronegativity rates of 13–20% and lower median antibody concentrations in seropositive individuals (449–773 IU/L). In these individuals, antibody levels decreased noticeably between the ages of 2 and 10 years but remained stable between those aged 10 and 30 years. There was no significant difference in seronegativity rates at the age of 12–24 months in children born 2016–2019 and 2020–2022 (the years of the COVID-19 pandemic). Conclusion: In Austria, there are significant immunity gaps in individuals born after 1970, which pre-existed before the COVID-19 pandemic. Thus, young and middle-aged populations not immune against measles should be vaccinated to counteract a further decline of immunity at the population level and prevent outbreaks whenever MeV is imported.

With the continuous emergence of novel SARS-CoV-2 variants, long-lasting and broadly reactive cellular and humoral immunity is critical for durable protection from COVID-19. We investigated SARS-CoV-2-specific T cell immunity in relation to antibodies, infection outcome and disease severity and assessed its durability in a longitudinal cohort over a three-year time course. We identified pre-existing T cells reactive to the seasonal coronavirus (CoV) OC43 that cross-react with the conserved SARS-CoV-2 spike S_813-829 peptide. These cross-reactive T cells increased in frequency following SARS-CoV-2 infection or vaccination and correlated with enhanced spike-specific T cell responses and significantly reduced viral loads. Furthermore, our data revealed that CoV-cross-reactive T cells were maintained as part of the long-lasting memory response, contributing to increased T cell frequencies against omicron variants. These findings suggest a functional role of CoV-cross-reactive T cells that extends beyond the initial SARS-CoV-2 exposure, contributing to enhanced immunity against highly mutated SARS-CoV-2 variants.

Tick-borne encephalitis (TBE) virus (TBEV) is transmitted to humans via tick bites. Infection is benign in >90% of the cases but can cause mild (<5%), moderate (<4%), or severe (<1%) encephalitis. We show here that ∼10% of patients hospitalized for severe TBE in cohorts from Austria, Czech Republic, and France carry auto-Abs neutralizing IFN-α2, -β, and/or -ω at the onset of disease, contrasting with only ∼1% of patients with moderate and mild TBE. These auto-Abs were found in two of eight patients who died and none of 13 with silent infection. The odds ratios (OR) for severe TBE in individuals with these auto-Abs relative to those without them in the general population were 4.9 (95% CI: 1.5–15.9, P < 0.0001) for the neutralization of only 100 pg/ml IFN-α2 and/or -ω, and 20.8 (95% CI: 4.5–97.4, P < 0.0001) for the neutralization of 10 ng/ml IFN-α2 and -ω. Auto-Abs neutralizing type I IFNs accounted for ∼10% of severe TBE cases in these three European cohorts.