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In this paper, the effects of wave–wave interactions of the lowest order, i.e., three-wave interactions, on parallel-propagating Alfvén wave spectra on a closed magnetic field line are considered. The spectra are then used to evaluate the transport parameters of energetic particles in a coronal loop. The wave spectral density is the main variable investigated, and it is modelled using a diffusionless numerical scheme. A model, where high-frequency Alfvén waves are emitted from the two footpoints of the loop and interact with each other as they pass by, is considered. The wave spectrum evolution shows the erosion of wave energy starting from higher frequencies so that the wave mode emitted from the closer footpoint of the loop dominates the wave energy density. Consistent with the cross-helicity state of the waves, the bulk velocity of energetic protons is from the loop footpoints towards the loop apex. Protons can be turbulently trapped in the loop, and Fermi acceleration is possible near the loop apex, as long as the partial pressure of the particles does not exceed that of the resonant waves. The erosion of the Alfvén wave energy density should also lead to the heating of the loop.

In autumn 2023, European vaccination campaigns predominantly administered XBB.1.5 vaccine. In a European multicentre study, we estimated 2023 COVID-19 vaccine effectiveness (VE) against laboratory-confirmed symptomatic infection at primary care level between September 2023 and January 2024. Using a test-negative case-control design, we estimated VE in the target group for COVID-19 vaccination overall and by time since vaccination. We included 1057 cases and 4397 controls. Vaccine effectiveness was 40 % (95 % CI: 26-53 %) overall, 48 % (95 % CI: 31-61 %) among those vaccinated < 6 weeks of onset and 29 % (95 % CI: 3-49 %) at 6-14 weeks. Our results suggest that COVID-19 vaccines administered to target groups during the autumn 2023 campaigns showed clinically significant effectiveness against laboratory-confirmed, medically attended symptomatic SARS-CoV-2 infection in the 3 months following vaccination. A longer study period will allow for further variant-specific COVID-19 VE estimates, better understanding decline in VE and informing booster administration policies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Importance: In the context of emerging SARS-CoV-2 variants or lineages and new vaccines, it is key to accurately monitor COVID-19 vaccine effectiveness (CVE) to inform vaccination campaigns., Objective: To estimate the effectiveness of COVID-19 vaccines administered in autumn and winter 2022 to 2023 against symptomatic SARS-CoV-2 infection (with all circulating viruses and XBB lineage in particular) among people aged 60 years or older in Europe, and to compare different CVE approaches across the exposed and reference groups used., Design, Setting, and Participants: This case-control study obtained data from VEBIS (Vaccine Effectiveness, Burden and Impact Studies), a multicenter study that collects COVID-19 and influenza data from 11 European sites: Croatia; France; Germany; Hungary; Ireland; Portugal; the Netherlands; Romania; Spain, national; Spain, Navarre region; and Sweden. Participants were primary care patients aged 60 years or older with acute respiratory infection symptoms who were recruited at the 11 sites after the start of the COVID-19 vaccination campaign from September 2022 to August 2023. Cases and controls were defined as patients with positive and negative, respectively, reverse transcription-polymerase chain reaction (RT-PCR) test results., Exposures: The exposure was COVID-19 vaccination. The exposure group consisted of patients who received a COVID-19 vaccine during the autumn and winter 2022 to 2023 vaccination campaign and 14 days or more before symptom onset. Reference group included patients who were not vaccinated during or in the 6 months before the 2022 to 2023 campaign (seasonal CVE), those who were never vaccinated (absolute CVE), and those who were vaccinated with at least the primary series 6 months or more before the campaign (relative CVE). For relative CVE of second boosters, patients receiving their second booster during the campaign were compared with those receiving 1 booster 6 months or more before the campaign., Main Outcomes and Measures: The outcome was RT-PCR-confirmed, medically attended, symptomatic SARS-CoV-2 infection. Four CVE estimates were generated: seasonal, absolute, relative, and relative of second boosters. CVE was estimated using logistic regression, adjusting for study site, symptom onset date, age, chronic condition, and sex., Results: A total of 9308 primary care patients were included, with 1687 cases (1035 females; median [IQR] age, 71 [65-79] years) and 7621 controls (4619 females [61%]; median [IQR] age, 71 [65-78] years). Within 14 to 89 days after vaccination, seasonal CVE was 29% (95% CI, 14%-42%), absolute CVE was 39% (95% CI, 6%-60%), relative CVE was 31% (95% CI, 15% to 44%), and relative CVE of second boosters was 34% (95% CI, 18%-47%) against all SARS-CoV-2 variants. In the same interval, seasonal CVE was 44% (95% CI, -10% to 75%), absolute CVE was 52% (95% CI, -23% to 82%), relative CVE was 47% (95% CI, -8% to 77%), and relative CVE of second boosters was 46% (95% CI, -13% to 77%) during a period of high XBB circulation. Estimates decreased with time since vaccination, with no protection from 180 days after vaccination., Conclusions and Relevance: In this case-control study among older Europeans, all CVE approaches suggested that COVID-19 vaccines administered in autumn and winter 2022 to 2023 offered at least 3 months of protection against symptomatic, medically attended, laboratory-confirmed SARS-CoV-2 infection. The effectiveness of new COVID-19 vaccines against emerging SARS-CoV-2 variants should be continually monitored using CVE seasonal approaches.

Background: Within influenza vaccine effectiveness (VE) studies at primary care level with a laboratory-confirmed outcome, clinical case definitions for recruitment of patients can vary. We used the 2022-23 VEBIS primary care European multicentre study end-of-season data to evaluate whether the clinical case definition affected IVE estimates., Methods: We estimated VE using a multicentre test-negative case-control design. We measured VE against any influenza and influenza (sub)types, by age group (0-14, 15-64, ≥65 years) and by influenza vaccine target group, using logistic regression. We estimated IVE among patients meeting the European Union (EU) acute respiratory infection (ARI) case definition and among those meeting the EU influenza-like illness (ILI) case definition, including only sites providing information on specific symptoms and recruiting patients using an ARI case definition (as the EU ILI case definition is a subset of the EU ARI one)., Results: We included 24 319 patients meeting the EU ARI case definition, of whom 21 804 patients (90 %) meet the EU ILI case definition, for the overall pooled VE analysis against any influenza. The overall and influenza (sub)type-specific VE varied by ≤2 % between EU ILI and EU ARI populations., Discussion: Among all analyses, we found similar VE estimates between the EU ILI and EU ARI populations, with few (10%) additional non-ILI ARI patients recruited. These results indicate that VE in the 2022-23 influenza season was not affected by use of a different clinical case definition for recruitment, although we recommend investigating whether this holds true for next seasons., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

BackgroundScarce European data in early 2021 suggested lower vaccine effectiveness (VE) against SARS-CoV-2 Omicron lineages than previous variants.AimWe aimed to estimate primary series (PS) and first booster VE against symptomatic BA.1/BA.2 infection and investigate potential biases.MethodsThis European test-negative multicentre study tested primary care patients with acute respiratory symptoms for SARS-CoV-2 in the BA.1/BA.2-dominant period. We estimated PS and booster VE among adults and adolescents (PS only) for all products combined and for Comirnaty alone, by time since vaccination, age and chronic condition. We investigated potential bias due to correlation between COVID-19 and influenza vaccination and explored effect modification and confounding by prior SARS-CoV-2 infection.ResultsAmong adults, PS VE was 37% (95% CI: 24-47%) overall and 60% (95% CI: 44-72%), 43% (95% CI: 26-55%) and 29% (95% CI: 13-43%) < 90, 90-179 and ≥ 180 days post vaccination, respectively. Booster VE was 42% (95% CI: 32-51%) overall and 56% (95% CI: 47-64%), 22% (95% CI: 2-38%) and 3% (95% CI: -78% to 48%), respectively. Primary series VE was similar among adolescents. Restricting analyses to Comirnaty had little impact. Vaccine effectiveness was higher among older adults. There was no signal of bias due to correlation between COVID-19 and influenza vaccination. Confounding by previous infection was low, but sample size precluded definite assessment of effect modification.ConclusionPrimary series and booster VE against symptomatic infection with BA.1/BA.2 ranged from 37% to 42%, with similar waning post vaccination. Comprehensive data on previous SARS-CoV-2 infection would help disentangle vaccine- and infection-induced immunity.

Influenza A viruses circulated in Europe from September 2023 to January 2024, with influenza A(H1N1)pdm09 predominance. We provide interim 2023/24 influenza vaccine effectiveness (IVE) estimates from two European studies, covering 10 countries across primary care (EU-PC) and hospital (EU-H) settings. Interim IVE was higher against A(H1N1)pdm09 than A(H3N2): EU-PC influenza A(H1N1)pdm09 IVE was 53% (95% CI: 41 to 63) and 30% (95% CI: -3 to 54) against influenza A(H3N2). For EU-H, these were 44% (95% CI: 30 to 55) and 14% (95% CI: -32 to 43), respectively.

Background: Influenza A(H3N2) viruses dominated early in the 2022-2023 influenza season in Europe, followed by higher circulation of influenza A(H1N1)pdm09 and B viruses. The VEBIS primary care network estimated the influenza vaccine effectiveness (VE) using a multicentre test-negative study., Materials and Methods: Primary care practitioners collected information and specimens from patients consulting with acute respiratory infection. We measured VE against any influenza, influenza (sub)type and clade, by age group, by influenza vaccine target group and by time since vaccination, using logistic regression., Results: We included 38 058 patients, of which 3786 were influenza A(H3N2), 1548 influenza A(H1N1)pdm09 and 3275 influenza B cases. Against influenza A(H3N2), VE was 36% (95% CI: 25-45) among all ages and ranged between 30% and 52% by age group and target group. VE against influenza A(H3N2) clade 2b was 38% (95% CI: 25-49). Overall, VE against influenza A(H1N1)pdm09 was 46% (95% CI: 35-56) and ranged between 29% and 59% by age group and target group. VE against influenza A(H1N1)pdm09 clade 5a.2a was 56% (95% CI: 46-65) and 79% (95% CI: 64-88) against clade 5a.2a.1. VE against influenza B was 76% (95% CI: 70-81); overall, 84%, 72% and 71% were among 0-14-year-olds, 15-64-year-olds and those in the influenza vaccination target group, respectively. VE against influenza B with a position 197 mutation of the hemagglutinin (HA) gene was 79% (95% CI: 73-85) and 90% (95% CI: 85-94) without this mutation., Conclusion: The 2022-2023 end-of-season results from the VEBIS network at primary care level showed high VE among children and against influenza B, with lower VE against influenza A(H1N1)pdm09 and A(H3N2)., Competing Interests: None., (© 2024 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Influenza virus-like particles (VLPs) represent an attractive alternative to traditional influenza vaccine formulations. Influenza VLPs mimic the natural virus while lacking the genetic material, are easily recognized by the immune system, and are considered safe. The use of a mammalian cell platform offers many advantages for VLP production, such as flexibility and the same glycosylation patterns as a human virus. In this study, the influenza VLPs containing hemagglutinin (HA), neuraminidase (NA) and matrix M1 proteins were expressed in CHO-K1, Vero or 293 T cell lines using transient transfection. After production in 3L bioreactor and purification, extensive characterization was performed on two batches of VLPs produced in 293 T, the best cell line for VLP expression; one batch expressed the HA and NA genes from A/Hong Kong/4801/2014 (H3N2) strain and the other, HA and NA genes from B/Phuket/3073/2013. Characterizations provided evidence that mammalian VLPs closely emulate the exterior of authentic virus particles in terms of both antigen presentation and biological properties. The two VLPs produced contained more NA proteins on their surface with a HA:NA ratio around 1:1 than influenza viruses which present a HA:NA ratio of around 4:1. Immunogenicity studies in BALB/c mice demonstrated that the VLPs, administered intra-muscularly, were highly immunogenic at low doses, with the induction of functional antibodies against HA and NA. Immunogenicity was also shown in a human in vitro model (MIMIC® system). In conclusion, we believe that influenza vaccines made of VLPs produced in mammalian cell lines, constitute a potential alternative to the classical influenza vaccines., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The NIH test is currently used to assess the potency of rabies vaccine, a key criterion for vaccine release. This test is based on mice immunization followed by intracerebral viral challenge. As part of global efforts to reduce animal experimentation and in the framework of the development of Sanofi Pasteur next generation, highly-purified vaccine, produced without any material of human or animal origin, we developed an ELISA as an alternative to the NIH test. This ELISA is based on monoclonal antibodies recognizing specifically the native form of the viral G-protein, the major antigen that induces neutralizing antibody response to rabies virus. We show here that our ELISA is able to distinguish between potent and different types of sub-potent vaccine lots. Satisfactory agreement was observed between the ELISA and the NIH test in the determination of the vaccine titer and their capacity to discern conform from non-conform batches. Our ELISA meets the criteria for a stability-indicating assay and has been successfully used to develop the new generation of rabies vaccine candidates. After an EPAA international pre-collaborative study, this ELISA was selected as the assay of choice for the EDQM collaborative study aimed at replacing the rabies vaccine NIH in vivo potency test., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)