Short-term Protection Research Articles

Protection of vaccine boosters and prior infection against mild/asymptomatic and moderate COVID-19 infection in the UK SIREN healthcare worker cohort: October 2023 to March 2024

ObjectivesBivalent original/BA.4-5 and monovalent XBB.1.5 mRNA boosters were offered to UK healthcare workers (HCWs) in autumn 2023. We aimed to estimate booster vaccine effectiveness (VE) and post-infection immunity among the SIREN HCW cohort over the subsequent 6-month period of XBB.1.5 and JN.1 variant circulation. MethodsBetween October 2023 to March 2024, 2,867 SIREN study participants tested fortnightly for SARS-CoV-2 and completed symptoms questionnaires. We used multi-state models, adjusted for vaccination, prior infection, and demographic covariates, to estimate protection against mild/asymptomatic and moderate SARS-CoV-2 infection. ResultsHalf of participants (1,422) received a booster during October 2023 (280 bivalent, 1,142 monovalent), and 536 (19%) had a PCR-confirmed infection over the study period. Bivalent booster VE was 15.1% (-55.4 to 53.6%) at 0-2 months and 4.2% (-46.4 to 37.3%) at 2-4 months post-vaccination. Monovalent booster VE was 44.2% (95% CI 21.7 to 60.3%) at 0-2 months, and 24.1% (-0.7 to 42.9%) at 2-4 months. VE was greater against moderate infection than against mild/asymptomatic infection, but neither booster showed evidence of protection after 4 months. Controlling for vaccination, compared to an infection >2 years prior, infection within the past 6 months was associated with 58.6% (30.3 to 75.4%) increased protection against moderate infection, and 38.5% (5.8 to 59.8%) increased protection against mild/asymptomatic infection. ConclusionsMonovalent XBB.1.5 boosters provided short-term protection against SARS-CoV-2 infection, particularly against moderate symptoms. Vaccine formulations which target the circulating variant may be suitable for inclusion in seasonal vaccination campaigns among HCWs.

Shifting sands: The influence of coral reefs on shoreline erosion from short-term storm protection to long-term disequilibrium

Climate change is exacerbating shoreline erosion and flooding, posing significant risks to coastal communities. Although traditional coastal defenses such as seawalls, dykes, and breakwaters offer protection from these hazards, their high environmental and economic costs are driving interest in cost-competitive nature-based solutions. Coral reef restoration is a nature-based solution that may be particularly apt to mitigate tropical coastal flooding and shoreline erosion while providing benefits to local tourism, fisheries, and nature. However, the novelty of this field requires studies demonstrating the benefits of reefs for coastal protection. While the flood protection benefits of reefs have been well-documented, their effects on shoreline erosion are comparatively less understood. Here, we investigate the effects of coral reefs on shoreline erosion by comparing tropical beach responses at short and long timescales, as well as identifying important reef structural features influencing coastal erosion rates. Our analyses leveraged two key datasets created in this study: the first derived from a literature review on short-term shoreline erosion due to storm events, and another compiling >80 years of long-term erosion rates, bathymetry, habitat, and wave energy for the Hawaiian Islands of Kauaʻi, Oʻahu, and Maui. Our analyses reveal three key findings regarding the effects of reefs on shoreline erosion. Firstly, we find evidence for the role of reefs in mitigating shoreline erosion during storm events, with coral reef-protected beaches experiencing 97 % less beach volume loss than unprotected beaches. Secondly, a linear regression analysis demonstrates that coral reef structure and wave energy are important predictors of long-term shoreline erosion rates, explaining 34 % of the variation across the Hawaiian Islands. Consistent with prior research, we find beaches protected by coral reefs with shallow reef crests, wide reef flats, calmer offshore conditions, and positioned farther from the shore exhibit lower erosion rates than others. Finally, when comparing historical erosion rates of protected and unprotected beaches in Hawai'i, we find a seemingly incongruous pattern where coral reef-protected beaches eroded up to 2x faster than beaches without reefs. While the cause of the enhanced erosion is yet to be fully understood, a combination of coral reef structural degradation and sea-level rise is likely shifting the equilibrium profiles of reef-protected beaches inshore. These results emphasize the role of coral reefs in reducing coastal erosion during storm events while revealing contrasting erosion patterns over long timescales. Future studies would ideally broaden the scope to include various regions, utilize advanced sediment transport models, and undertake field experiments to deepen our understanding of coral reef-coupled shoreline dynamics.

Ad Hoc Adaptations to Climate Change in Coastal Communities

Climate change disproportionately impacts coastal residents in the United States. Existing studies document institutional efforts to adapt to sea level rise through projects like seawalls, beach nourishment, and property acquisitions to protect communities from rising seas. Such studies capture institutional adaptations, but do not include ad hoc adaptations by homeowners impacted by climate change. How are homeowners adapting to climate hazards? This paper analyzes ethnographic and interview data from 100 households in two coastal counties in North Carolina, a state with one of the most climate vulnerable shorelines in the country. This analysis of homeowner response considers ad hoc adaptations along the North Carolina coast. Results show that homeowners recognize climate hazards and regularly adapt on their own within the context of institutionally maintained flood protection infrastructure and transportation access to the places where they live. Residents are aware of and attempt to access support for home adaptations when programs or funds are available to them after disasters and do so with varying levels of success, though the more pervasive adaptations to chronic stress are not supported by government programs or insurance mechanisms. Ad hoc adaptations may provide short-term protection from climate hazards but have questionable long-term efficacy as sea levels rise and storm strength and frequency increases. Leaving communities and households to adapt on their own as chronic climate hazards outpace institutional response exacerbates existing inequalities by relying on residents with different levels of resources and agency to adapt.

Comprehensive Review of Recent Advances in Nanoparticle-Based Corrosion Inhibition Approaches

Corrosion of metals is a persistent challenge in various industries, leading to significant economic losses and safety hazards. Conventional corrosion inhibitors often face limitations such as environmental toxicity, low efficiency, and short-term protection. Nanoparticle-based corrosion inhibitors have emerged as a promising alternative due to their unique properties and versatile applications. This paper provides a comprehensive review of the recent advances in nanoparticle-based corrosion inhibition strategies from 2015-2024 by harvesting data from secondary sources. The fundamental mechanisms underlying the corrosion inhibition by nanoparticles are discussed, including adsorption processes, passivation mechanisms, and synergistic effects with other inhibitors. Various types of nanoparticles, including metallic nanoparticles, metal oxide nanoparticles, polymer nanocomposites, carbon-based nanoparticles, and organic-inorganic hybrid nanoparticles, are explored for their corrosion inhibition potential. Furthermore, the applications of nanoparticle-based corrosion inhibitors in industries such as oil and gas, aerospace, automotive, marine, and infrastructure are highlighted. Despite significant progress, challenges such as stability, compatibility, and environmental concerns remain to be addressed. Future directions in nanoparticle-based corrosion inhibition research are also discussed, aiming to guide further developments in this promising field.

Learning from the COVID-19 Pandemic: Next-generation universal vaccines and immunotherapeutic research

Learning from the COVID-19 Pandemic: Next-generation universal vaccines and immunotherapeutic research With the COVID-19 pandemic behind us, we need to focus on universal vaccines and/or immunotherapeutic strategies and technologies to tackle ongoing endemic infections with SARS-CoV2, influenza, and RSV and prepare for any future pandemics, says Dr Babita Agrawal. In the 21st century, we have witnessed the emergence of respiratory infections with pandemic potential, like corona and influenza viruses, on multiple occasions. Due to the global dissemination of one such coronavirus, SARS-CoV2 (severe acute respiratory syndrome-coronavirus type-2), the World Health Organization (WHO) declared a worldwide pandemic in March 2020. The global public health emergency was declared over in May 2023 by the WHO, but infections with variants of SARS-CoV2 continue to evolve and cause infections worldwide. (1) Besides public health measures, developing, approving, and implementing vaccines against SARS-CoV2 have helped mitigate and end the pandemic. However, the existing vaccines against SARS-CoV2 are not preventive, do not induce mucosal immunity, induce only short-term protection and are ineffective against emerging variants, thereby requiring regular updated boosters.

Odourless vegetable oils as insect pest repellents for short-term protection of various food packaging materials

The repellent activity of two odourless vegetable oils (sweet almond—SAO and soybean—SO) applied on filter paper and four types of food packaging materials (polyethylene film, plastic gunnysacks, cardboard, and wood) was tested against three species of stored product pests (Sitophilus granarius, Tribolium castaneum, and Oryzaephilus surinamensis). The repellence of three doses was evaluated after 24 h, and after 7, 14, 21, and 28 days. Both oils exhibited a repellent effect when applied to filter paper, but this effect decreased with time and concentration. The most susceptible species was T. castaneum. The maximum repellence was 84% and 76% for SO and SAO, respectively. On packaging materials, the repellent effect diminished after a certain period of time, ranging from 7 to 28 days. Subsequently, the oils even became attractive. Generally, the repellent effects of both SO and SAO were higher on cardboard and wood slab than on polyethylene film and plastic gunnysacks. As such, in the case of SO, the repellence against T. castaneum was 88% 24 h after application on cardboard, whilst 68% on plastic bag. This work demonstrated the repellent potential of vegetable oils in the short term for the protection of packaged food against stored product pests.

Alexis® Orthopedic Protector Provides Wound Protection and Aids in Hypertrophic Scar Prevention in Total Hip Arthroplasty.

Total hip arthroplasty (THA) is one of the most widely performed orthopedic surgeries. Techniques for small skin incisions and preservation of muscles and tendons have been developed. However, avoiding skin complications and muscle damage due to forced deployment and surgical manipulation is challenging. This study aimed to investigate whether the use of Alexis® Orthopedic Protector (Applied Medical Resources Corp., Rancho Santa Margarita, CA, USA) affects postoperative outcomes. This was a retrospective cohort study including 118 patients who underwent primary THA by the same surgeon at our single institution between March 2021 and March 2023. Protectors were used alternately for each operation. Fifty-nine patients were in the protector-using group (P group), and 59 were in the nonprotector-using group (N group), with comparisons made between groups. Protectors were placed under the fascia in all patients. Preoperative blood tests showed no difference in renal and hepatic function between the two groups. No differences in postoperative C-reactive protein (CRP) and creatine kinase (CK) values or in the Japanese Orthopedic Association Hip Disease Evaluation Questionnaire (JHEQ) and Numerical Rating Scale (NRS) scores were observed. Postoperative redness was significantly higher in the N group than in the P group (49.2% vs. 7%). The percentage of hypertrophic scars at three months postoperatively was 18.6% in the N group and 7% in the P group. Furthermore, the Japan Scar Workshop Scar Scale (JSS) indicated that hypertrophic scars were significantly worse in the N group than in the P group (p = 0.0012). Alexis® Orthopedic Protectors can not only provide short-term wound protection but also reduce the rate and degree of hypertrophic scarring.

Sustained release of inactivated H1N1 virus from degradable microparticles for extended vaccination

Influenza vaccines administered as intramuscularly injected inactivated viruses or intranasally administered live-attenuated viruses usually provide short-term protection against influenza infections. Biodegradable particles that provide sustained release of the antigen has been studied as an approach to extend vaccine protection. Here, we investigate sustained release of ultraviolet killed influenza A virus (A/PR/8/34(H1N1)) (kPR8) loaded into poly(D,L-lactic-co-glycolic acid) (PLGA) microparticles. Particles were prepared using the double emulsion method, and polymer molecular weight (MW), polymer hydrophobicity, polymer concentration in the organic phase, and the amount of killed virus were varied to obtain a range of particles. Formulations included PLGA 50:50 (2–6, 7–17 kDa), PLGA 75:25 (4–15 kDa), and 50/50 PLGA 75:25 (4–15 kDa)/PCL (14 kDa). Additionally, NaOH was co-encapsulated in some cases to enhance particle degradation. The structure of the particles was explored by size measurements and electron microscopy. The kPR8 release profiles were measured using hemagglutinin ELISA. The concentration of the polymer (PLGA) in the organic phase and polymer MW significantly influenced virus loading, while polymer MW and co-encapsulation of NaOH modulated the release profiles. Mice receiving a single intramuscular injection of NaOH microparticle-encapsulated kPR8 were partially protected against a lethal influenza challenge 32 weeks post immunization. Microparticle (MP) vaccination induced a gradual increase in PR8-specific IgGs dominated by IgG1 in contrast to the rapid IgG2a-biased response elicited by soluble kPR8 immunization. Our results indicate that vaccine-NaOH co-loaded PLGA particles show potential as a single dose vaccination strategy for extended protection against influenza virus infection.

Investigation of COVID-19 transmission during the first community outbreak in a remote island population, Falkland Islands, April to June 2022.

After 2 years of no community outbreaks of COVID-19, the Falkland Islands (FI) reported their first community case in April 2022. Because of high vaccine coverage (88% of entire population), no specific control measures were instigated, and cases spread rapidly. We undertook a retrospective cohort study to determine the extent of transmission and the effectiveness of COVID-19 vaccine in a population with limited natural immunity. We extracted data on age, sex, and vulnerability for the FI registered population from a patient information system and linked to COVID-19 case line-list and vaccination datasets. Cases were individuals with positive SARS-CoV-2 PCRs or Lateral Flow Devices (LFDs), from 26 April to 30 June 2022. Univariable analyses compared case risk factors to non-cases. Relative vaccine effectiveness was calculated using Poisson regression with robust error variance, comparing against individuals with vaccination more than the 20 weeks prior to the outbreak. Models were adjusted for age, sex, extreme vulnerability, and previous infection. Of the 3,343 registered population, 44% (n = 1,467) were cases, with no COVID-19 hospitalisations or deaths. In univariable analysis, being female (RR 1.12, p = 0.004) and under 18 years (RR 1.70, p<0.001) were associated with increased COVID-19 risk. Relative vaccine effectiveness was 39.0% (95% CI, 1.03 to 62.5) and 33.0% (95% CI, 8.3 to 51.0) 1 to 9 weeks after receiving 2nd and 1st boosters respectively. We showed widespread transmission in a small island population with limited natural immunity, disproportionately affecting children and women, indicative of transmission in educational and household settings. Despite limited natural immunity, our findings suggested that vaccination was effective protecting against severe disease and booster doses provided additional short-term protection against infection. We would recommend optimizing coverage with boosters of vaccine in remote island populations such as FI. Follow-up would be needed to assess duration of protection after booster vaccination.

Imiquimod powder for inhalation to stimulate innate immunity

Literature data suggest that toll-like receptor agonists administered by inhalation stimulate innate immunity, providing broad-spectrum, short-term protection against infectious diseases. They are promising also to improve the course of diseases, as adjuvants in allergen immunotherapy, and in association with antigens in inhalation vaccines. Imiquimod, an agonist of toll-like receptors 7 and 8, is currently FDA-approved for topical administration. This work aimed to design an IMQ powder for inhalation to stimulate the immune response in the airways for broad-spectrum, short-term protection against infections, to fight infectious diseases, and/or as adjuvant in allergen immunotherapy, as well as in vaccines for pulmonary administration. Highly respirable and crystalline imiquimod microparticles were produced via spray drying and micronization. The microparticles are suitable for inhalation both alone and in adhesive mixtures with coarse lactose. In vitro studies proved the powders' non-cytotoxicity and ability to induce a controlled production of inflammatory cytokines.

Replicon particle vaccination induces non-neutralizing anti-nucleoprotein antibody-mediated control of Crimean-Congo hemorrhagic fever virus

Crimean-Congo hemorrhagic fever virus (CCHFV) can cause severe human disease and is considered a WHO priority pathogen due to the lack of efficacious vaccines and antivirals. A CCHF virus replicon particle (VRP) has previously shown protective efficacy in a lethal Ifnar-/- mouse model when administered as a single dose at least 3 days prior to challenge. Here, we determine that non-specific immune responses are not sufficient to confer short-term protection, since Lassa virus VRP vaccination 3 days prior to CCHFV challenge was not protective. We also investigate how CCHF VRP vaccination confers protective efficacy by examining viral kinetics, histopathology, clinical analytes and immunity early after challenge (3 and 6 days post infection) and compare to unvaccinated controls. We characterize how these effects differ based on vaccination period and correspond to previously reported CCHF VRP-mediated protection. Vaccinating Ifnar-/- mice with CCHF VRP 28, 14, 7, or 3 days prior to challenge, all known to confer complete protection, significantly reduced CCHFV viral load, mucosal shedding, and markers of clinical disease, with greater reductions associated with longer vaccination periods. Interestingly, there were no significant differences in innate immune responses, T cell activation, or antibody titers after challenge between groups of mice vaccinated a week or more before challenge, but higher anti-NP antibody avidity and effector function (ADCD) were positively associated with longer vaccination periods. These findings support the importance of antibody-mediated responses in VRP vaccine-mediated protection against CCHFV infection.

Expression and purification of an NP-hoc fusion protein: Utilizing influenza a nucleoprotein and phage T4 hoc protein

Influenza poses a substantial health risk, with infants and the elderly being particularly susceptible to its grave impacts. The primary challenge lies in its rapid genetic evolution, leading to the emergence of new Influenza A strains annually. These changes involve punctual mutations predominantly affecting the two main glycoproteins: Hemagglutinin (HA) and Neuraminidase (NA). Our existing vaccines target these proteins, providing short-term protection, but fall short when unexpected pandemics strike. Delving deeper into Influenza's genetic makeup, we spotlight the nucleoprotein (NP) - a key player in the transcription, replication, and packaging of RNA. An intriguing characteristic of the NP is that it is highly conserved across all Influenza A variants, potentially paving the way for a more versatile and broadly protective vaccine. We designed and synthesized a novel NP-Hoc fusion protein combining Influenza A nucleoprotein and T4 phage Hoc, cloned using Gibson assembly in E. coli, and purified via ion affinity chromatography. Simultaneously, we explore the T4 coat protein Hoc, typically regarded as inconsequential in controlled viral replication. Yet, it possesses a unique ability: it can link with another protein, showcasing it on the T4 phage coat. Fusing these concepts, our study designs, expresses, and purifies a novel fusion protein named NP-Hoc. We propose this protein as the basis for a new generation of vaccines, engineered to guard broadly against Influenza A. The excitement lies not just in the immediate application, but the promise this holds for future pandemic resilience, with NP-Hoc marking a significant leap in adaptive, broad-spectrum influenza prevention.

Effects of selective serotonin reuptake inhibitors (SSRIs) on suicide: A network meta-analysis of double-blind randomized trials

The relationship between the use of selective serotonin reuptake inhibitors (SSRIs) and suicide risk in patients with mental disorders remains controversial. We conducted a network meta-analysis to examine the effects of SSRIs on suicide risk in patients with mental disorders. A comprehensive search was conducted across PubMed, Web of Science, PsycINFO, CENTRAL, Wanfang Database, and China National Knowledge Infrastructure for articles published until December 19, 2023. The main outcomes were suicidal ideation and instances of suicidal behavior. We included 29 double-blind randomized trials in our analysis. The findings suggest that SSRIs primarily offer short-term protection against suicidal ideation. By week 2, paroxetine, fluoxetine, escitalopram, and non-SSRI treatments were linked to a decreased suicide risk compared with a placebo, with the exception of sertraline. This protective effect was diminished by week 8. In contrast, studies on instances of suicidal behavior from weeks 1 to 10 found no significant difference in efficacy between SSRIs, non-SSRIs, and placebo. These results indicate that SSRIs may offer short-term protection against suicidal ideation. However, their long-term effectiveness in mitigating suicidal ideation and preventing suicidal behaviors is limited.

Cinnamon Bark Oil as an Effective Fungicide in Protecting the Surface of Wood-Based Softboards against the Development of Mold Fungi

Porous wood-based boards, like any lignocellulosic material, are susceptible to biocorrosion caused by mold fungi. Their durability can be extended by using biocides. Due to the fact that porous boards are considered an ecological material, it would be beneficial to also use natural agents to protect them. For this purpose, the surface of softboards was protected with a 30% solution of cinnamon bark oil in ethanol. Three application levels were used: 75 g/m2, 120 g/m2, and 200 g/m2 of solution. It has been shown that the cinnamon bark oil solution used at an application rate of 200 g/m2 is an effective fungicide, protecting softboards (SBs) against the development of mold fungi: T. viride and C. globosum. The dominant volatile component of cinnamon oil identified in the boards turned out to be cinnamaldehyde. Three months after treatment, this substance constituted 74% of the volatile components. The proposed treatment method allows for short-term preventive protection of boards against mold fungi.

Delivery of Agarose-aided Sprays to the Posterior Nose for Mucosa Immunization and Short-term Protection against Infectious Respiratory Diseases.

The study aimed to deliver sprays to the posterior nose for mucosa immunization or short-term protection. Respiratory infectious diseases often enter the human body through the nose. Sars- Cov-2 virus preferentially binds to the ACE2-rich tissue cells in the Nasopharynx (NP). Delivering medications to the nose, especially to the NP region, provides either a short-term protective/ therapeutic layer or long-term mucosa immunization. Hydrogel-aided medications can assist film formation, prolong film life, and control drug release. However, conventional nasal sprays have failed to dispense mediations to the posterior nose, with most sprays lost in the nasal valve and front turbinate. The objective of the study was to develop a practical delivery system targeting the posterior nose and quantify the dosimetry distribution of agarose-saline solutions in the nasal cavity. The solution viscosities with various hydrogel concentrations (0.1-1%) were measured at different temperatures. Dripping tests on a vertical plate were conducted to understand the hydrogel concentration effects on the liquid film stability and mobility. Transparent nasal airway models were used to visualize the nasal spray deposition and liquid film translocation. Spray dosimetry with different hydrogel concentrations and inhalation flow rates was quantified on a total and regional basis. The solution viscosity increased with decreasing temperature, particularly in the range of 60-40oC. The liquid viscosity, nasal spray atomization, and liquid film mobility were highly sensitive to the hydrogel concentration. Liquid film translocations significantly enhanced delivered doses to the caudal turbinate and nasopharynx when the sprays were administered at 60oC under an inhalation flow rate of 11 L/min with hydrogel concentrations no more than 0.5%. On the other hand, sprays with 1% hydrogel or administered at 40oC would significantly compromise the delivered doses to the posterior nose. Delivering sufficient doses of hydrogel sprays to the posterior nose is feasible by leveraging the post-administration liquid film translocation.

Early skin inflammatory biomarker is predictive of development and persistence of atopic dermatitis in infants

BackgroundThe STOP AD study, a randomized, open-label trial evaluating the effect of short-term (first four postnatal days to 8 weeks) skin barrier protection using AVEENO® Dermexa Fast & Long-Lasting Balm in infants with a parent with allergic disease, demonstrated decreased cumulative incidence and decreased prevalence of AD at 12 months of age. ObjectiveWe aimed to identify skin biomarkers in the STOP AD study that are associated with risk of development of AD. MethodsSkin swabs were collected from the cheek and antecubital fossa (AF) at baseline, 8 weeks, and 12 months from subsets of study participants from each of the intervention arm (43 of 119) and control arm (43 of 138) and were analyzed for specific cytokines (CCL27, CXCL2, hBD1, IL18, IL8, IL1α, IL1RA, IL1β, S100A8/9, IL36γ) by ELISA. ResultsHigher titers of S100A8/9 at the AF at 8 weeks in infants with filaggrin wild type genotype (FLGwt), but not in those with filaggrin loss-of-function mutations (FLGmut), predicted: 1) Development of AD in the first year of life (p=0.033); 2) Presence of AD at 6 months or 12 months of age (p=0.009 and 0.035, respectively); 3) Persistence of AD between 6 and 12 months of age (p<0.001); 4) Development of AD with the emollient intervention. ConclusionIncreased titers of S100A8/9 from skin swabs of the AF in high-risk infants at 8 weeks with FLGwt was predictive of AD developing in the first year of life and of other AD features. These findings suggest that there are different molecular pathways leading to AD in FLGmut individuals and in FLGwt individuals. Early identification of infants who are likely to develop AD will allow more targeted interventions.

A novel lentiviral vector-based approach to generate chimeric antigen receptor T cells targeting Aspergillus fumigatus.

Invasive aspergillosis (IA) is a common and deadly mold infection in immunocompromised patients. As morbidity and mortality of IA are primarily driven by poor immune defense, adjunct immunotherapies, such as chimeric antigen receptor (CAR) T cells, are direly needed. Here, we propose a novel approach to generate Aspergillus fumigatus (AF)-CAR T cells using the single-chain variable fragment domain of monoclonal antibody AF-269-5 and a lentiviral vector system. These cells successfully targeted mature hyphal filaments of representative clinical and reference AF isolates and elicited a potent release of cytotoxic effectors and type 1 T cell cytokines. Furthermore, AF-CAR T cells generated from peripheral blood mononuclear cells of four healthy human donors and expanded with either of three cytokine stimulation regimens (IL-2, IL-2 + IL-21, or IL-7 + IL-15) significantly suppressed mycelial growth of AF-293 after 18 hours of co-culture and synergized with the immunomodulatory antifungal agent caspofungin to control hyphal growth for 36 hours. Moreover, cyclophosphamide-immunosuppressed NSG mice with invasive pulmonary aspergillosis that received two doses of 5 million AF-CAR T cells (6 and 48 hours after AF infection) showed significantly reduced morbidity on day 4 post-infection (P < 0.001) and significantly improved 7-day survival (P = 0.049) compared with mice receiving non-targeting control T cells, even without concomitant antifungal chemotherapy. In conclusion, we developed a novel lentiviral strategy to obtain AF-CAR T cells with high targeting efficacy, yielding significant anti-AF activity in vitro and short-term protection in vivo. Our approach could serve as an important steppingstone for future clinical translation of antifungal CAR T-cell therapy after further refinement and thorough preclinical evaluation.IMPORTANCEInvasive aspergillosis (IA) remains a formidable cause of morbidity and mortality in patients with hematologic malignancies and those undergoing hematopoietic stem cell transplantation. Despite the introduction of several new Aspergillus-active antifungals over the last 30 years, the persisting high mortality of IA in the setting of continuous and profound immunosuppression is a painful reminder of the major unmet need of effective antifungal immune enhancement therapies. The success of chimeric antigen receptor (CAR) T-cell therapy in cancer medicine has inspired researchers to translate this approach to opportunistic infections, including IA. Aiming to refine anti-Aspergillus CAR T-cell therapy and improve its feasibility for future clinical translation, we herein developed and validated a novel antibody-based CAR construct and lentiviral transduction method to accelerate the production of CAR T cells with high targeting efficacy against Aspergillus fumigatus. Our unique approach could provide a promising platform for future clinical translation of CAR T-cell-based antifungal immunotherapy.

Previous SARS-CoV-2 infections and their impact on the protection from reinfection during the Omicron BA.5 wave – a nested case-control study among vaccinated adults in Sweden

ObjectivesWe evaluated the protection afforded by SARS-CoV-2 infection-induced immunity against reinfection among working-age vaccinated individuals during a calendar period from June to December 2022 when Omicron BA.5 was the dominating subvariant in Scania County, Sweden. MethodsThe study cohort (n = 71,592) mainly consisted of health care workers. We analyzed 4144 infected cases during the Omicron BA.5 dominance and 41,440 sex- and age-matched controls with conditional logistic regression. ResultsThe average protection against reinfection was marginal (16%, 95% confidence interval [CI] 7-23%) during the study period but substantially higher for recent infections. Recent infection (3-6 months) with Omicron BA.2 and BA.5 offered strong protection (86%, 95% CI 68-94% and 78%, 95% CI 69-84%), whereas more distant infection (6-12 months) with Omicron BA.1, BA.2, and the variants before Omicron offered marginal or no protection. ConclusionsThese findings suggest that infection-induced immunity contributes to short-term population protection against infection with the subvariant BA.5 among working-age vaccinated individuals but wanes considerably with time, independent of the virus variant.

COVID-19 vaccination: are more jabs needed or are we now immune?

As the COVID-19 pandemic has progressed, it has become apparent that COVID-19 vaccination has limited impact on SAR-CoV-2 transmission and provides only short-term protection against acquiring infection, but more robust protection against severe disease and death. As a result, vaccinated people remain susceptible to SARS-CoV-2 infection but are less likely to experience severe outcomes. Studies show that immunity derived from the combination of vaccination and natural infection, so-called hybrid immunity, is superior to that provided by vaccination or natural infection alone. Since most Australian adults have received three or more doses of COVID-19 vaccines and >70% have also been infected with SARS-CoV-2, we now have a population with high levels of hybrid immunity. This was mostly achieved by receiving original Wuhan strain vaccines and then experiencing Omicron strain infections. The original Wuhan strain of SARS-CoV-2 has now disappeared and been replaced with Omicron-lineage variants globally. The predominance of the Omicron strain initially led to the development of bivalent vaccines containing both the Wuhan strain and Omicron variants. Currently, vaccines containing the original Wuhan strain of spike protein are being phased out, and new COVID-19 vaccines based exclusively on the Omicron strain XBB have become available in Australia. This article explores the question of whether further doses will be required from 2024 onwards and, if so, who should receive them?

Effectiveness of the adapted bivalent mRNA COVID-19 vaccines against hospitalisation in individuals aged ≥ 60 years during the Omicron XBB lineage-predominant period: VEBIS SARI VE network, Europe, February to August, 2023.

We conducted a multicentre hospital-based test-negative case-control study to measure the effectiveness of adapted bivalent COVID-19 mRNA vaccines against PCR-confirmed SARS-CoV-2 infection during the Omicron XBB lineage-predominant period in patients aged ≥ 60 years with severe acute respiratory infection from five countries in Europe. Bivalent vaccines provided short-term additional protection compared with those vaccinated > 6 months before the campaign: from 80% (95% CI: 50 to 94) for 14-89 days post-vaccination, 15% (95% CI: -12 to 35) at 90-179 days, and lower to no effect thereafter.