Moderate Protection Research Articles

Protective effects of E. coli Nissle 1917 on chickens infected with Salmonella pullorum

The probiotic E. coli Nissle 1917 (EcN) plays an important role in regulating the microbial components of the gut and preventing inflammation of the gastrointestinal tract. Currently, the long-term use of antibiotics for the treatment of lethal white diarrhea in chicks caused by Salmonella has led to increased morbidity and mutation rates. Therefore, we want to use EcN as an antibiotic alternative as an alternative approach to prevent Salmonella-induced white diarrhea in chickens. To date, there are no reports of EcN being used for the prevention and control of Salmonella pullorum (S. pullorum) in chickens. In vitro, pretreatment with EcN significantly decreased the cellular invasion of S. pullorum CVCC533 in a chicken fibroblast (DF-1) cell model. Then, 0-day-old egg-laying chickens were orally inoculated with EcN at a dose of 109 CFU/100 μL at either Day 1 (EcN1) or both Day 1 and Day 4 (EcN2). Then, S. pullorum CVCC533 was used to challenge the cells at a dose of 1.0 × 107 CFU/100 μL on Day 8. Next, the body weights and survival rates were recorded for 14 consecutive days, and the colonization of S. pullorum in the spleen and liver at 7 days post-challenge (dpc) was determined. Chicken feces were also collected at 2, 4, 6 and 8 dpc to evaluate the excretion of pathogenic bacteria in feces. The liver, duodenum and rectum samples were collected and analyzed by pathological histology at 7 dpc to evaluate the protective effect of EcN on the mucosa, villi and crypts of the small intestine. The spleen and bursa were collected, and the immune organ index was calculated. In addition, the contents of the cecum of chicks were collected at 7 dpc for 16S rRNA sequencing to detect the distribution of microbial communities in the intestine. The results showed that EcN was able to protect against CVCC533 challenge, as shown by decreased body weight loss, mortality and shedding of pathogenic bacteria in fecal samples in the EcN1 plus Salmonella challenge group (EcN1S) but not the EcN2 plus Salmonella challenge group (EcN2S). The pathogenic changes in the liver, duodenum and rectum also demonstrated that one dose but not two doses of EcN effectively prolonged the length of the pilus with decreased crypt depth, indicating its protective effects against S. pullorum. In addition, the 16S rRNA sequencing results suggested that EcN could enlarge the diversity of intestinal flora, decrease the abundance of pathogenic bacteria and increase the abundance of beneficial bacteria, such as Lactobacillus. In conclusion, EcN has shown moderate protection against S. pullorum challenge in chickens.

COVID-19 vaccination protects children and adolescents

By February 2022, European and US agencies recommended use of the BNT162b2 mRNA COVID-19 vaccine (Pfizer–BioNTech) as a primary two-dose series in children aged 5–11 years and as a booster dose in adolescents aged 12–15 years.1–2 Since then, some real-world BNT162b2 vaccine effectiveness data among children and adolescents have generally showed moderate protection against symptomatic infection,3–6 with better protection against COVID-19-associated serious outcomes (emergency department visits and hospitalisations),6–9 especially in the weeks immediately after vaccination.

The efficacy of the prime-boost regimen for heterologous infectious bronchitis vaccines mandates the administration of homologous vaccines.

Infectious bronchitis virus (IBV) has been frequently reported in chickens worldwide, including in the Eastern Region of Saudi Arabia (ERS). Several IBV outbreaks were recently reported in chickens despite the massive use of various vaccines. Based on partial sequencing of the S1 gene, at least three genotypes were reported (CK/CH/LDL/97I, IS/720/99, and IS/Variant2/98) in the ERS with no available homologous vaccines. Herein, we tried to evaluate the protection provided by some selected commercial-available vaccines against these three genotypes. We divided the experimental chickens into eight groups. Representative isolates from these genotypes were inoculated into three groups of broiler chickens vaccinated with the H-120 vaccine at the age of 1 day and boosted with the 4/91 vaccine at the age of 14 days (challenged groups). One group of chickens had received the same protocol of IBV vaccines but was kept without infection to serve as a vaccine control group. The three isolates were inoculated into three other similar but unvaccinated groups of broiler chickens (infected groups). Group eight chickens were neither vaccinated nor infected and used as a negative control group. Evaluation of the protection induced by the tested vaccination schedule was assessed by several criteria, including the ability to reduce the severe clinical signs caused by IBV infection, changes in the body temperature of various groups of chickens, the reduction in the magnitude of IBV-induced lesions, and the reduction in the viral loads in tracheas of a different group of chicken. Monitoring the immune status of chickens was also recorded based on the hemagglutination inhibition antibodies in sera of various groups of chickens. Our results show clinical and tracheal protection against IBV/IS/Variant2/98-like and IBV/IS/720/99-like strains. Moderate protection was observed in the IBV/CK/CH/LDL/97I-like pressure. The kidneys of the challenged groups of chickens showed minimal or no gross lesions compared with the infected groups, even in those chickens challenged with the IBV/CK/CH/LDL/97I-like strain. In conclusion, this is the first study to perform the protectotyping of some IBV strains from Saudi Arabia. It demonstrated the proficiency of the investigated vaccination schedule in control of infection of broiler chickens with IBV/IS/Variant2/98 and IBV/IS/720/99 strains. It is highly recommended to introduce the homologous IBV/CK/CH/LDL/97I-based vaccine to the vaccination protocols of chickens in the ERS to match the circulating strains and ensure better protection.

KANDUNGAN FITOKIMIA DAN NILAI SUN PROTECTION FACTORS (SPF) PADA EKSTRAK METANOL Hypnea pannosa, Turbinaria decurrens, DAN Caulerpa serrulata. (PHYTOCHEMICAL CONTENT AND VALUE OF SUN PROTECTION FACTORS (SPF) IN METHANOL EXTRACTS OF Hypnea pannosa, Turbinaria decurrens, AND Caulerpa serrulata)

Seaweed grows abundantly in Indonesian waters. Seaweed is an important commodity and valuable for the cosmetic industry. The aim of this research was to determine the phytochemical content and SPF value of the methanol extract of seaweeds, namely Caulerpa serrulata, Turbinaria decurrens, and Hypnea pannosa. The sample was macerated with methanol solvent. The methanol extract of C. serrulata obtained the highest yield of 4.42 g. The results of phytochemical screening on C. serrulata, T. decurrens, and H. pannosa contains alkaloids, flavonoids, terpenoids, tannins, and saponins. The SPF of methanol extract was analyzed by UV-Vis Spectrophotometer. SPF values with a concentration of 100 ppm were obtained for C. serrulata (4.80), T. deccurens (0.81), and H. pannosa (0.80). The methanol extract from C. serrulata was the highest SPF. It was categorized in the moderate protection category.

Less is more: repellent-treated fabric strips as a substitute for full screening of open eave gaps for indoor and outdoor protection from malaria mosquito bites

BackgroundProviding protection from malaria vector bites, both indoors and outdoors, is crucial to curbing malaria parasite transmission. Screening of house entry points, especially with incorporated insecticides, confers significant protection but remains a costly and labour-intensive application. Use of spatial repellents has shown promise in creating areas of protection in peri-domestic areas.MethodsThis study aimed at comparing the protection provided by transfluthrin-treated and untreated complete screens over open eave gaps with incomplete transfluthrin-treated eave strips as a potential replacement for a full screen. Human landing catches were implemented independently inside and outside an experimental hut under controlled semi-field conditions, with insectary-reared Anopheles arabiensis mosquitoes.ResultsThe odds of a female mosquito finding a human volunteer indoors and attempting to bite were similar whether the eaves were completely open or there was an untreated fabric strip fixed around the eaves. However, when the eave gap was completely screened without insecticide, the odds of receiving a bite indoors were reduced by 70% (OR 0.30, 95% CI 0.20–0.47). Adding transfluthrin to the full screen, further increased the protection indoors, with the odds of receiving a bite reduced by 92% (0.08, 95% CI 0.04–0.16) compared to the untreated screen. Importantly, the same protection was conferred when only a narrow transfluthrin-treated fabric strip was loosely fixed around the eave gap (OR 0.07, 95% CI 0.04–0.13). The impact of the transfluthrin treatment on outdoor biting was correlated with evening temperatures during the experiments. At lower evening temperatures, a transfluthrin-treated, complete screen provided moderate and variable protection from bites (OR 0.62, 95% CI 0.37–1.03), whilst at higher evening temperatures the odds of receiving a bite outdoors was over four times lower in the presence of transfluthrin, on either a full screen (OR 0.22 95% 0.12–0.38) or a fabric strip (OR 0.25, 95% 0.15–0.42), than when no treatment was present.ConclusionThe findings suggest that transfluthrin-treated fabric strips can provide a substitute for complete eave screens. They are a simple, easy-to-handle tool for protecting people from malaria mosquito bites indoors and potentially around the house in climatic areas where evening and night-time temperatures are relatively high.

Efficacy of Chitosan-PLGA encapsulated trivalent oral vaccine against viral haemorrhagic septicemia virus, Streptococcus parauberis, and Miamiensis avidus in olive flounder (Paralichthys olivaceus)

The present study was conducted to assess the protective efficacy of a trivalent oral vaccine containing chitosan–PLGA encapsulated inactivated viral haemorrhagic septicemia virus (VHSV), Streptococcus parauberis serotype I and Miamiensis avidus antigens, followed by its oral (incorporated in feed) administration to olive flounder (Paralichthys olivaceus) fingerlings for a period of 15-consecutive days. After 35 days of initial vaccination, three separate challenge studies were conducted at the optimal temperature of the targeted pathogens using an intraperitoneal injection route. RPS analysis revealed moderate protection in the immunized group against all the three pathogens viz., VHSV (53.30% RPS), S. parauberis serotype-I (33.30% RPS), and M. avidus (66.75% RPS), as compared to the respective non-vaccinated challenge (NVC) control group. In addition, the immunized fish demonstrated significantly (p < 0.05) higher specific antibody titres in serum and significant (p < 0.05) upregulation in the transcript levels of immune genes of Igs (IgM, IgT, pIgR), TLRs (TLR 2, TLR 7), cytokines (IL-1β, IL-8) and complement pathway (C3) in the mucosal and systemic tissues than those of NVC control fish, suggesting orchestration of pathogen-specific host immune responses thereby favouring its combativeness against the three pathogens. The expression dynamics of IFN-γ, Mx, caspase 3 genes post VHSV challenge; IFN-γ, TLR 2, caspase 1 genes post S. parauberis serotype I challenge and CD-8α, IL-10, TNF-α genes post M. avidus challenge further substantiates the efficacy of the vaccine in stimulating antiviral, antibacterial and antiparasitic immune responses in the host resulting in their better survival. The findings from the present study reflect that the formulated trivalent oral vaccine incorporating VHSV, S. parauberis serotype I and M. avidus antigens can be a promising prophylactic strategy to prevent the associated disease outbreaks in olive flounder.

Determination of SPF value in Serum Preparation of Ethyl acetat fraction ethanol extract of Roselle Petals (Hibiscus sabdarifa L.)

The ethyl acetate fraction of the ethanol extract of roselle flower petals (Hibiscus sabdariffa L.) was reported to have an SPF value of 13.83 ± 1.50 which was higher than the ethanol extract. So with the SPF value, the ethyl acetate fraction of roselle flower ethanol extract can be used as a sunscreen. One of the cosmetic preparations that is currently growing rapidly is serum. The purpose of this study was to formulate the ethyl acetate fraction of roselle petals into a serum that had good physical quality with variations in the concentration of xanthan gum and then the SPF value was determined. This research begins with the manufacture of ethanol extract of roselle petals. Then fractionation (liquid-liquid partition) was carried out using solvents with different polarities, namely n-hexane and ethyl acetate. Furthermore, the ethyl acetate fraction was formulated into serum with variations in the concentration of xanthan gum 0.3%, respectively; 0.6% and 1.2% were then tested for physical quality and stability. The next step is to determine the SPF value of the serum by using the UV spectrophotometric method and its calculation using the Mansur equation. The results showed that the serum ethyl acetate fraction of the ethanolic extract of roselle petals could be made into gel preparations with good physical qualities including organoleptic, viscosity, pH and homogeneity. Serum ethyl acetate fraction ethanol extract of roselle flower formulas 1, 2 and 3 had SPF values F1 respectively, namely 6.8595 ± 0.08 which included moderate protection potential; F2 is 7.0089 ± 0.17; and F3 which is 8.2251 ± 0.32 with extra protection potential. Variations in the concentration of xanthan gum in the serum formula affect the physical quality of the viscosity and potency of sunscreen preparations..

Immune Response against Hepatitis B Vaccine in Transfusion-Dependent Thalassemic Children Vaccinated in Early Infancy

Background and Objectives: Children with thalassemia are much more vulnerable to being infected by hepatitis B virus (HBV) through transfusion of blood and blood products. Although active immunization against HBV in early infancy is being conducted in Bangladesh by the inclusion of the hepatitis B vaccine (HepB) in the expanded programme on immunization schedule, these children might have altered immune response against HepB due to inevitable iron overload resulting from the disease thalassemia itself as well as repeated transfusion therapy and also from exposure to different allogeneic antigens. The present study was designed to determine the immune response of HepB among transfusion-dependent thalassemic children. Patients and Methods: This cross-sectional study was conducted at a university hospital in Bangladesh. A total of 45 transfusion-dependent thalassemic children were included according to inclusion and exclusion criteria. Data collection was conducted through a structured questionnaire after taking written informed consent from each participant's guardian. Each patient underwent a detailed history taking and antibody to hepatitis B surface antigen (anti-HBs) titer was estimated to see the immune response against HepB. Results: Collected data were analyzed using SPSS version 23. The mean age of the studied children was 9.03 ± 3.78 standard deviation with slight female predominance (51.1% female and 48.9% male). According to the level of anti-HBs titer, the majority (44.4%) had moderate protection, whereas others had no (28.9%) or strong (26.7%) protection. No significant association between the total number of transfusions (approximate), different age groups, and postvaccination interval with anti-HBs titer was observed (P &gt; 0.05). Conclusion: The present study observed an overall poor immune response against HepB as approximately only one-fourth of the study participants got strong protection against HBV. Assessment of anti-HBs titer followed by booster dose or revaccination if necessary is needed to be considered in transfusion-dependent thalassemic children vaccinated in early infancy.

BNT162b2 Vaccine Effectiveness against Omicron in Children 5 to 11 Years of Age

BackgroundLimited evidence is available on the real-world effectiveness of the BNT162b2 vaccine against coronavirus disease 2019 (Covid-19) and specifically against infection with the omicron variant among children 5 to 11 years of age.MethodsUsing data from the largest health care organization in Israel, we identified a cohort of children 5 to 11 years of age who were vaccinated on or after November 23, 2021, and matched them with unvaccinated controls to estimate the vaccine effectiveness of BNT162b2 among newly vaccinated children during the omicron wave. Vaccine effectiveness against documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and symptomatic Covid-19 was estimated after the first and second vaccine doses. The cumulative incidence of each outcome in the two study groups through January 7, 2022, was estimated with the use of the Kaplan–Meier estimator, and vaccine effectiveness was calculated as 1 minus the risk ratio. Vaccine effectiveness was also estimated in age subgroups.ResultsAmong 136,127 eligible children who had been vaccinated during the study period, 94,728 were matched with unvaccinated controls. The estimated vaccine effectiveness against documented infection was 17% (95% confidence interval [CI], 7 to 25) at 14 to 27 days after the first dose and 51% (95% CI, 39 to 61) at 7 to 21 days after the second dose. The absolute risk difference between the study groups at days 7 to 21 after the second dose was 1905 events per 100,000 persons (95% CI, 1294 to 2440) for documented infection and 599 events per 100,000 persons (95% CI, 296 to 897) for symptomatic Covid-19. The estimated vaccine effectiveness against symptomatic Covid-19 was 18% (95% CI, −2 to 34) at 14 to 27 days after the first dose and 48% (95% CI, 29 to 63) at 7 to 21 days after the second dose. We observed a trend toward higher vaccine effectiveness in the youngest age group (5 or 6 years of age) than in the oldest age group (10 or 11 years of age).ConclusionsOur findings suggest that as omicron was becoming the dominant variant, two doses of the BNT162b2 messenger RNA vaccine provided moderate protection against documented SARS-CoV-2 infection and symptomatic Covid-19 in children 5 to 11 years of age. (Funded by the European Union through the VERDI project and others.)

Indigenous-led conservation: Pathways to recovery for the nearly extirpated Klinse-Za mountain caribou.

Indigenous Peoples around the northern hemisphere have long relied on caribou for subsistence and for ceremonial and community purposes. Unfortunately, despite recovery efforts by federal and provincial agencies, caribou are currently in decline in many areas across Canada. In response to recent and dramatic declines of mountain caribou populations within their traditional territory, West Moberly First Nations and Saulteau First Nations (collectively, the “Nations”) came together to create a new vision for caribou recovery on the lands they have long stewarded and shared. The Nations focused on the Klinse‐Za subpopulation, which had once encompassed so many caribou that West Moberly Elders remarked that they were “like bugs on the landscape.” The Klinse‐Za caribou declined from ~250 in the 1990s to only 38 in 2013, rendering Indigenous harvest of caribou nonviable and infringing on treaty rights to a subsistence livelihood. In collaboration with many groups and governments, this Indigenous‐led conservation initiative paired short‐term population recovery actions, predator reduction and maternal penning, with long‐term habitat protection in an effort to create a self‐sustaining caribou population. Here, we review these recovery actions and the promising evidence that the abundance of Klinse‐Za caribou has more than doubled from 38 animals in 2013 to 101 in 2021, representing rapid population growth in response to recovery actions. With looming extirpation averted, the Nations focused efforts on securing a landmark conservation agreement in 2020 that protects caribou habitat over a 7986‐km2 area. The Agreement provides habitat protection for >85% of the Klinse‐Za subpopulation (up from only 1.8% protected pre‐conservation agreement) and affords moderate protection for neighboring caribou subpopulations (29%–47% of subpopulation areas, up from 0%–20%). This Indigenous‐led conservation initiative has set both the Indigenous and Canadian governments on the path to recover the Klinse‐Za subpopulation and reinstate a culturally meaningful caribou hunt. This effort highlights how Indigenous governance and leadership can be the catalyst needed to establish meaningful conservation actions, enhance endangered species recovery, and honor cultural connections to now imperiled wildlife.

Duration of mRNA vaccine protection against SARS-CoV-2 Omicron BA.1 and BA.2 subvariants in Qatar

SARS-CoV-2 Omicron BA.1 and BA.2 subvariants are genetically divergent. We conducted a matched, test-negative, case-control study to estimate duration of protection of the second and third/booster doses of mRNA COVID-19 vaccines against BA.1 and BA.2 infections in Qatar. BNT162b2 effectiveness was highest at 46.6% (95% CI: 33.4–57.2%) against symptomatic BA.1 and at 51.7% (95% CI: 43.2–58.9%) against symptomatic BA.2 infections in the first three months after the second dose, but declined to ~10% or below thereafter. Effectiveness rebounded to 59.9% (95% CI: 51.2–67.0%) and 43.7% (95% CI: 36.5–50.0%), respectively, in the first month after the booster dose, before declining again. Effectiveness against COVID-19 hospitalization and death was 70–80% after the second dose and >90% after the booster dose. mRNA-1273 vaccine protection showed similar patterns. mRNA vaccines provide comparable, moderate, and short-lived protection against symptomatic BA.1 and BA.2 Omicron infections, but strong and durable protection against COVID-19 hospitalization and death.

Comprehensive Assessment of Lightning Protection Schemes for 10 kV Overhead Distribution Lines

This paper presents an assessment of lightning protection schemes for overhead lines from two aspects: protection performance and economic cost. Considering the random nature of lightning, the Monte-Carlo method with a heuristic technique is applied in the assessment. The one-dimensional finite-difference time-domain method is adopted to evaluate lightning overvoltages on insulators and lightning currents in surge arresters for failure assessment. The failure rate of an overhead line is addressed under both direct lightning and indirect lightning. A reduced set of design parameters are identified. It is found that the line insulation itself with a critical flashover overvoltage of less than 200 kV is not sufficient for lightning protection, especially against direct strokes. With other protection options, however, increasing the insulation level can greatly improve the protection performance. Installing surge arresters on every pole results in the best protection performance, but could be extremely expensive due to the replacement of failed surge arresters. The shielding wire provides moderate protection performance with a relatively low cost. The combination of the shielding wire and surge arresters provides much better performance under a wide range of soil conductivity with a moderate cost. It is worth mentioning that adopting high insulation strength for overhead lines in the new-line design could lead to significant cost savings for lightning protection. Guidelines for selecting design parameter values and protection schemes are provided, as well as a procedure for performance-cost evaluation.

MAEBL Contributes to Plasmodium Sporozoite Adhesiveness.

The sole currently approved malaria vaccine targets the circumsporozoite protein—the protein that densely coats the surface of sporozoites, the parasite stage deposited in the skin of the mammalian host by infected mosquitoes. However, this vaccine only confers moderate protection against clinical diseases in children, impelling a continuous search for novel candidates. In this work, we studied the importance of the membrane-associated erythrocyte binding-like protein (MAEBL) for infection by Plasmodium sporozoites. Using transgenic parasites and live imaging in mice, we show that the absence of MAEBL reduces Plasmodium berghei hemolymph sporozoite infectivity to mice. Moreover, we found that maebl knockout (maebl-) sporozoites display reduced adhesion, including to cultured hepatocytes, which could contribute to the defects in multiple biological processes, such as in gliding motility, hepatocyte wounding, and invasion. The maebl- defective phenotypes in mosquito salivary gland and liver infection were reverted by genetic complementation. Using a parasite line expressing a C-terminal myc-tagged MAEBL, we found that MAEBL levels peak in midgut and hemolymph parasites but drop after sporozoite entry into the salivary glands, where the labeling was found to be heterogeneous among sporozoites. MAEBL was found associated, not only with micronemes, but also with the surface of mature sporozoites. Overall, our data provide further insight into the role of MAEBL in sporozoite infectivity and may contribute to the design of future immune interventions.

A Modified Surgical Face Mask to Improve Protection and Wearing Comfort

Wearing face masks is essential for reducing infection during the COVID-19 pandemic. However, ordinary surgical face masks can provide only moderate protection. The N95 face masks should provide sufficient protection but may impose complaints about breathing difficulty or even impair respiratory health. This investigation proposed a novel face mask modified from the surgical face mask to improve both protection and comfort. The filter material of the surgical face mask was covered and sealed on a cardboard support frame but with openings for air permeating through. The modified face masks were worn by a test subject for measuring the air contents inside the face masks. The protection performance was evaluated by the overall PM1 filtration efficiency. The concentrations of CO2, O2, N2, and water vapor were adopted to evaluate the breathing comfort. The performance of the proposed face mask was compared with the market-available surgical and N95 face masks. In addition, CFD modeling was adopted to investigate the dynamic air exchange of the face mask with respiration and the surrounding air. Impacts of the air sampling tube positions on the measurement results were also examined. The results revealed that the overall PM1 filtration efficiency of the modified face mask could reach 96.2%, which was much higher than that of the surgical face mask and only slightly lower than the N95 face mask. As compared with the N95 face mask, the modified mask reduced the respiratory flow resistance and the concentrations of CO2 and water vapor and thus increased the O2 content and breathing comfort.

Live-attenuated influenza vaccine effectiveness against hospitalization in children aged 2-6years, the first three seasons of the childhood influenza vaccination program in England, 2013/14-2015/16.

IntroductionIn 2013, the United Kingdom began to roll‐out a universal annual influenza vaccination program for children. An important component of any new vaccination program is measuring its effectiveness. Live‐attenuated influenza vaccines (LAIVs) have since shown mixed results with vaccine effectiveness (VE) varying across seasons and countries elsewhere. This study aims to assess the effectiveness of influenza vaccination in children against severe disease during the first three seasons of the LAIV program in England.MethodsUsing the screening method, LAIV vaccination coverage in children hospitalized with laboratory‐confirmed influenza infection was compared with vaccination coverage in 2–6‐year‐olds in the general population to estimate VE in 2013/14–2015/16.ResultsThe overall LAIV VE, adjusted for age group, week/month and geographical area, for all influenza types pooled over the three influenza seasons was 50.1% (95% confidence interval [CI] 31.2, 63.8). By age, there was evidence of protection against hospitalization from influenza vaccination in both the pre‐school (2–4‐year‐olds) (48.1%, 95% CI 27.2, 63.1) and school‐aged children (5–6‐year‐olds) (62.6%, 95% CI 2.6, 85.6) over the three seasons.ConclusionLAIV vaccination in children provided moderate annual protection against laboratory‐confirmed influenza‐related hospitalization in England over the three influenza seasons. This study contributes further to the limited literature to date on influenza VE against severe disease in children.

Effectiveness of BNT162b2 and ChAdOx-1 vaccines in residents of long-term care facilities in England using a time-varying proportional hazards model.

Introductionresidents of long-term care facilities (LTCFs) are at high risk of adverse outcomes from SARS-CoV-2. We aimed to estimate the vaccine effectiveness (VE) of one and two doses of BNT162b2 and ChAdOx-1 against SARS CoV-2 infection and COVID-19-related death in residents of LTCFs.Methodsthis observational study used testing, vaccination and mortality data for LTCF residents aged ≥ 65 years who were regularly tested regardless of symptoms from 8 December 2020 to 30 September 2021 in England. Adjusted VE, calculated as one minus adjusted hazard ratio, was estimated using time-varying Cox proportional hazards models for infection and death within 28 days of positive test result. Vaccine status was defined by receipt of one or two doses of vaccine and assessed over a range of intervals.Resultsof 197,885 LTCF residents, 47,087 (23.8%) had a positive test and 11,329 (5.8%) died within 28 days of a positive test during the study period. Relative to unvaccinated individuals, VE for infection was highest for ChAdOx-1 at 61% (40–74%) at 1–4 weeks and for BNT162b2 at 69% (52–80%) at 11–15 weeks following the second dose. Against death, VE was highest for ChAdOx-1 at 83% (58–94%) at 1–4 weeks and for BNT162b2 at 91% (75–97%) at 11–15 weeks following second dose.Conclusionscompared with unvaccinated residents, vaccination with one dose of BNT162b2 or ChAdOx-1 provided moderate protection against infection and death in residents of LTCFs. Protection against death improved after two doses. However, some waning of protection over time was noted.

A modified vaccinia Ankara vaccine expressing spike and nucleocapsid protects rhesus macaques against SARS-CoV-2 Delta infection.

SARS-CoV-2 vaccines should induce broadly cross-reactive humoral and T cell responses to protect against emerging variants of concern (VOCs). Here, we inactivated the furin-cleavage site (FCS) of spike expressed by a modified vaccinia Ankara (MVA) virus vaccine (MVA/SdFCS) and found that FCS inactivation markedly increased spike binding to human ACE2. Following vaccination of mice, the MVA/SdFCS vaccine induced 8-fold higher neutralizing antibodies compared to MVA/S, which expressed spike without FCS inactivation, and protected against the beta variant. We next added nucleocapsid to the MVA/SdFCS vaccine (MVA/SdFCS-N) and tested its immunogenicity and efficacy via intramuscular (IM), buccal (BU) or sublingual (SL) routes in rhesus macaques. IM vaccination induced spike-specific IgG in serum and mucosae (nose, throat, lung, rectum) which neutralized the homologous (WA-1/2020) and heterologous VOCs, including delta, with minimal loss (<2-fold) of activity. IM vaccination also induced both S and N specific CD4 and CD8 T cell responses in the blood. In contrast, the SL and BU vaccinations induced less spike-specific IgG in secretions and lower levels of polyfunctional IgG in serum compared to IM vaccination. Following challenge with SARS-CoV-2 delta variant, the IM route induced robust protection, BU moderate protection and the SL no protection. Vaccine-induced neutralizing and non-neutralizing antibody effector functions positively correlated with protection, but only the effector functions correlated with early protection. Thus, IM vaccination with MVA/SdFCS-N vaccine elicited cross-reactive antibody and T cell responses, protecting against heterologous SARS-CoV-2 VOC more effectively than other routes of vaccination.

Conservation of birds in fragmented landscapes requires protected areas

For successful conservation of biodiversity, it is vital to know whether protected areas in increasingly fragmented landscapes effectively safeguard species. However, how large habitat fragments must be, and what level of protection is required to sustain species, remains poorly known. We compiled a global dataset on almost 2000 bird species in 741 forest fragments varying in size and protection status, and show that protection is associated with higher bird occurrence, especially for threatened species. Protection becomes increasingly effective with increasing size of forest fragments. For forest fragments &gt;50 ha our results show that strict protection (International Union for Conservation of Nature [IUCN] categories I–IV) is strongly associated with higher bird occurrence, whereas fragments had to be at least 175 ha for moderate protection (IUCN categories V and VI) to have a positive effect. This meta‐analysis quantifies the importance of fragment size, protection status, and their interaction for the conservation of bird species communities, and stresses that protection should not be limited to large pristine areas.

Effectiveness of Pneumococcal Conjugate Vaccination Against Virus-Associated Lower Respiratory Tract Infection Among Adults: A Case-Control Study.

BackgroundInteractions of Streptococcus pneumoniae with viruses feature in the pathogenesis of numerous respiratory illnesses.MethodsWe undertook a case-control study among adults at Kaiser Permanente Southern California between 2015 and 2019. Case patients had diagnoses of lower respiratory tract infection (LRTI; including pneumonia or nonpneumonia LRTI diagnoses), with viral infections detected by multiplex polymerase chain reaction testing. Controls without LRTI diagnoses were matched to case patients by demographic and clinical attributes. We measured vaccine effectiveness (VE) for 13-valent (PCV13) against virus-associated LRTI by determining the adjusted odds ratio for PCV13 receipt, comparing case patients and controls.ResultsPrimary analyses included 13 856 case patients with virus-associated LRTI and 227 887 matched controls. Receipt of PCV13 was associated with a VE of 24.9% (95% confidence interval, 18.4%–30.9%) against virus-associated pneumonia and 21.5% (10.9%–30.9%) against other (nonpneumonia) virus-associated LRTIs. We estimated VEs of 26.8% (95% confidence interval, 19.9%–33.1%) and 18.6% (9.3%–27.0%) against all virus-associated LRTI episodes diagnosed in inpatient and outpatient settings, respectively. We identified statistically significant protection against LRTI episodes associated with influenza A and B viruses, endemic human coronaviruses, parainfluenza viruses, human metapneumovirus, and enteroviruses but not respiratory syncytial virus or adenoviruses.ConclusionsAmong adults, PCV13 conferred moderate protection against virus-associated LRTI. The impacts of pneumococcal conjugate vaccines may be mediated, in part, by effects on polymicrobial interactions between pneumococci and respiratory viruses.

Comparative analysis of the risks of hospitalisation and death associated with SARS-CoV-2 omicron (B.1.1.529) and delta (B.1.617.2) variants in England: a cohort study

SummaryBackgroundThe omicron variant (B.1.1.529) of SARS-CoV-2 has demonstrated partial vaccine escape and high transmissibility, with early studies indicating lower severity of infection than that of the delta variant (B.1.617.2). We aimed to better characterise omicron severity relative to delta by assessing the relative risk of hospital attendance, hospital admission, or death in a large national cohort.MethodsIndividual-level data on laboratory-confirmed COVID-19 cases resident in England between Nov 29, 2021, and Jan 9, 2022, were linked to routine datasets on vaccination status, hospital attendance and admission, and mortality. The relative risk of hospital attendance or admission within 14 days, or death within 28 days after confirmed infection, was estimated using proportional hazards regression. Analyses were stratified by test date, 10-year age band, ethnicity, residential region, and vaccination status, and were further adjusted for sex, index of multiple deprivation decile, evidence of a previous infection, and year of age within each age band. A secondary analysis estimated variant-specific and vaccine-specific vaccine effectiveness and the intrinsic relative severity of omicron infection compared with delta (ie, the relative risk in unvaccinated cases).FindingsThe adjusted hazard ratio (HR) of hospital attendance (not necessarily resulting in admission) with omicron compared with delta was 0·56 (95% CI 0·54–0·58); for hospital admission and death, HR estimates were 0·41 (0·39–0·43) and 0·31 (0·26–0·37), respectively. Omicron versus delta HR estimates varied with age for all endpoints examined. The adjusted HR for hospital admission was 1·10 (0·85–1·42) in those younger than 10 years, decreasing to 0·25 (0·21–0·30) in 60–69-year-olds, and then increasing to 0·47 (0·40–0·56) in those aged at least 80 years. For both variants, past infection gave some protection against death both in vaccinated (HR 0·47 [0·32–0·68]) and unvaccinated (0·18 [0·06–0·57]) cases. In vaccinated cases, past infection offered no additional protection against hospital admission beyond that provided by vaccination (HR 0·96 [0·88–1·04]); however, for unvaccinated cases, past infection gave moderate protection (HR 0·55 [0·48–0·63]). Omicron versus delta HR estimates were lower for hospital admission (0·30 [0·28–0·32]) in unvaccinated cases than the corresponding HR estimated for all cases in the primary analysis. Booster vaccination with an mRNA vaccine was highly protective against hospitalisation and death in omicron cases (HR for hospital admission 8–11 weeks post-booster vs unvaccinated: 0·22 [0·20–0·24]), with the protection afforded after a booster not being affected by the vaccine used for doses 1 and 2.InterpretationThe risk of severe outcomes following SARS-CoV-2 infection is substantially lower for omicron than for delta, with higher reductions for more severe endpoints and significant variation with age. Underlying the observed risks is a larger reduction in intrinsic severity (in unvaccinated individuals) counterbalanced by a reduction in vaccine effectiveness. Documented previous SARS-CoV-2 infection offered some protection against hospitalisation and high protection against death in unvaccinated individuals, but only offered additional protection in vaccinated individuals for the death endpoint. Booster vaccination with mRNA vaccines maintains over 70% protection against hospitalisation and death in breakthrough confirmed omicron infections.FundingMedical Research Council, UK Research and Innovation, Department of Health and Social Care, National Institute for Health Research, Community Jameel, and Engineering and Physical Sciences Research Council.