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For COVAIL recipients of a COVID-19 Sanofi booster vaccine, neutralizing antibody titers were assessed as a correlate of risk (CoR) of COVID-19. Peak and exposure-proximal titers were inverse CoRs with covariate-adjusted hazard ratios (95% confidence intervals) 0.30 (0.11, 0.78) and 0.25 (0.07, 0.85) per 10-fold increase in weighted average titer.
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The present study investigates the impact of varying concentrations of PVC microplastics (PVC-MPs) - specifically 0 (no PVC-MPs), 2, and 4 mg L- 1 -alongside different arsenic (As) levels of 0 (no As), 150, and 300 mg kg- 1 in the soil, with the concurrent application of copper oxide-nanoparticles (CuO-NPs) at 0 (no CuO -NPs), 25 and 50 µg mL- 1 to barley (Hordeum vulgare L.) plants. This research primarily aims to assess plant growth and biomass, photosynthetic pigments and gas exchange characteristics, oxidative stress indicators, as well as the response of various antioxidants (both enzymatic and non-enzymatic) and their relevant genes expression, proline metabolism, the AsA-GSH cycle, and cellular fractionation within the plants. The findings showed that increased levels of PVC-MPs and As stress in the soil significantly reduced plant growth and biomass, photosynthetic pigments, and gas exchange characteristics. Additionally, PVC-MPs and As stress increased oxidative stress in the roots and shoots, as evidenced by elevated levels of malondialdehyde (MDA), hydrogen peroxide (H2O2), and electrolyte leakage (EL), which in turn stimulated the production of various enzymatic and non-enzymatic antioxidants, gene expression, and sugar content. Furthermore, a notable increase in proline metabolism, the AsA-GSH cycle, and cellular pigmentation was observed. Conversely, the application of CuO-NPs resulted in a substantial improvement in plant growth and biomass, gas exchange characteristics, and the activity of enzymatic and non-enzymatic antioxidants, along with a reduction in oxidative stress. Additionally, CuO-NPs enhanced cellular fractionation while decreasing proline metabolism and the AsA-GSH cycle in H. vulgare plants. These outcomes provide new insights into sustainable agricultural practices and offer significant potential in addressing the critical challenges of heavy metal contamination in agricultural soils.
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Arsénico , Biodegradación Ambiental , Cobre , Hordeum , Microplásticos , Estrés Oxidativo , Cobre/metabolismo , Hordeum/efectos de los fármacos , Hordeum/metabolismo , Hordeum/crecimiento & desarrollo , Estrés Oxidativo/efectos de los fármacos , Contaminantes del Suelo , Cloruro de Polivinilo , Nanopartículas , Antioxidantes/metabolismo , Nanopartículas del MetalRESUMEN
We compared the serologic responses of 1 dose versus 2 doses of a variant vaccine (Moderna mRNA-1273 Beta/Omicron BA.1 bivalent vaccine) in adults. A 2-dose boosting regimen with a variant vaccine did not increase the magnitude or the durability of the serological responses compared to a single variant vaccine boost.
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Vacuna nCoV-2019 mRNA-1273 , Adulto , Humanos , Vacunas Combinadas , Protocolos Clínicos , ARN Mensajero/genéticaRESUMEN
In a randomized clinical trial, we compare early neutralizing antibody responses after boosting with bivalent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccines based on either BA.1 or BA.4/BA.5 Omicron spike protein combined with wild-type spike. Responses against SARS-CoV-2 variants exhibited the greatest reduction in titers against currently circulating Omicron subvariants for both bivalent vaccines.
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COVID-19 , Humanos , COVID-19/prevención & control , SARS-CoV-2/genética , Anticuerpos Neutralizantes , Vacunas Combinadas , Anticuerpos AntiviralesRESUMEN
OBJECTIVE: To provide physicians with an understanding of the factors behind significant delays in the diagnosis of hidradenitis suppurativa (HS) in France. PATIENTS AND METHODS: This prospective multicentre national study conducted from October 2015 to March 2016 included all patients consulting for HS. Patient data were collected by means of a standardized questionnaire. Univariate and multivariate analyses were conducted to collect factors associated with a significant time to diagnosis of at least 5.5years, defined as the period between the onset of initial clinical signs and the time of formal diagnosis. RESULTS: The 16 participating centres enrolled 312 patients (62% women), of average age 35years. The average age at onset of HS was 22years. Before formal diagnosis by a dermatologist (64% of cases), 170 (54%), 114 (37%) and 45 (15%) patients had previously consulted at least 3, 5 and 10 general physicians, respectively. The average time between the initial clinical signs of HS, the first dermatology visit and the definitive diagnosis was 6.2 and 8.4 years, respectively. Active smoking (OR adjusted 1.85; P=0.027) and disease onset at a younger age (adjusted OR 0.92; P<0.001) were both associated with significant delays in diagnosis. CONCLUSION: These results emphasized misdiagnosis among HS patients but did not evidence any association between either sociodemographic or economic characteristics and the existence of significant times to diagnosis.
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Diagnóstico Tardío , Errores Diagnósticos , Hidradenitis Supurativa/diagnóstico , Adulto , Edad de Inicio , Estudios Transversales , Femenino , Francia/epidemiología , Humanos , Masculino , Estudios Prospectivos , Fumar/epidemiologíaRESUMEN
AIM: This novel multiparameter Phase I study aimed to optimize doses/dosing schedules of everolimus and sorafenib drug combination, based on modeling/simulation (NCT01932177). PATIENTS & METHODS: About 26 patients with solid tumors were treated in four different dosing schedules. Everolimus once daily + sorafenib twice daily were given continuously in arms A and B, and intermittently in arms C (alternating every other week) and D (everolimus continuous and sorafenib 3 days on/4 days off). RESULTS: Continuous schedules exhibited higher toxicity risks than intermittent schedules (64.1 vs 35.9%; p < 0.0001), and trends for lower disease control rates (80 vs 100%). No significant pharmacokinetic interaction was identified. CONCLUSION: Feasibility of EVESOR trial is demonstrated. Intermittent schedules might provide better tolerance and efficacy than continuous schedules.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Esquema de Medicación , Everolimus/administración & dosificación , Everolimus/farmacocinética , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neoplasias/diagnóstico , Niacinamida/administración & dosificación , Niacinamida/análogos & derivados , Niacinamida/farmacocinética , Compuestos de Fenilurea/administración & dosificación , Compuestos de Fenilurea/farmacocinética , Inhibidores de Proteínas Quinasas/administración & dosificación , Sorafenib , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
This study aimed to investigate the anti-depressant effect of hesperidin (Hsp) in streptozotocin (STZ)-induced diabetic rats. Additionally, the effect of Hsp on hyperglycaemia, oxidative stress, inflammation, brain-derived neurotrophic factor (BDNF), and brain monoamines in diabetic rats was also assessed. The Wistar rats in the experimental groups were rendered hyperglycaemic with a single dose of STZ (52.5 mg·(kg body mass)(-1), by intraperitoneal injection). The normal group received the vehicle only. Hyperglycaemic rats were treated with Hsp (25.0, 50.0, or 100.0 mg·(kg body mass)(-1)·day(-1), per oral) and fluoxetine (Flu) (5.0 mg·(kg body mass)(-1)·day(-1), per oral) 48 h after the STZ injection, for 21 consecutive days. The normal and STZ control groups received the vehicle (distilled water). Behavioral and biochemical parameters were then assessed. When Hsp was administered to the STZ-treated rats, this reversed the STZ-induced increase in immobility duration in the forced swimming test (FST) and attenuated hyperglycaemia, decreased malondialdehyde (MDA), increased reduced glutathione (GSH) decreased interleukin-6 (IL-6), and increased BDNF levels in the brain. Treatment with Hsp attenuated STZ-induced neurochemical alterations, as indicated by increased levels of monoamines in the brain, namely, norepinephrine (NE), dopamine (DA), and serotonin (5-hydroxytryptamine; 5-HT). All of these effects of Hsp were similar to those observed with the established anti-depressant Flu. This study shows that Hsp exerted anti-depressant effect in diabetic rats, which may have been partly mediated by its amelioration of hyperglycaemia as well as its anti-oxidant and anti-inflammatory activities, the enhancement of neurogenesis, and changes in the levels of monoamines in the brain.
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Antidepresivos/uso terapéutico , Conducta Animal/efectos de los fármacos , Depresión/tratamiento farmacológico , Diabetes Mellitus Experimental/tratamiento farmacológico , Hesperidina/uso terapéutico , Animales , Antidepresivos/farmacología , Monoaminas Biogénicas/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Depresión/psicología , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/psicología , Fluoxetina/farmacología , Fluoxetina/uso terapéutico , Glutatión/metabolismo , Hesperidina/farmacología , Hiperglucemia/tratamiento farmacológico , Hiperglucemia/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Interleucina-6/metabolismo , Masculino , Malondialdehído/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas Wistar , EstreptozocinaRESUMEN
The rising demand for safe plant compounds and herbal products that contribute positively to human health is in line with current market trends. Plants belonging to the Satureja genus, particularly the aromatic medicinal S. montana L. from the Lamiaceae family, are well suited to these trends as they serve as pharmaceutical raw materials. This research aimed to assess the influence of sowing date and fertilization doses, as well as their interaction, on the fresh weight, essential oil content, and composition of S. montana. Experimental cultivation involved varying nitrogen and phosphorus levels. The second cut had the highest fresh weight and oil production compared to the first cut. The highest total plant biomass was achieved with autumn sowing and fertilization at 55 kg N/ha and 37 kg P/ha, whereas Spring sowing exhibited higher essential oil production, with the maximum oil % with 74 kg P/ha and oil yield after applying 55 kg N/ha and 74 kg P/ha. The GC-MS analysis revealed that carvacrol was the predominant compound, with it being recommended to grow S. montana in Spring at doses of 55 kg N/ha and 74 kg P/ha for the superior oil yield. Additionally, S. montana essential oil demonstrated notable biological and antimicrobial activity, positioning it as a potential alternative to chemical food preservatives.
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Background: Phytogenic feed additives are products derived from plants used to improve the performance and health of animals. Nowadays, this type of phytogenic feed additive is widely used as an alternative to antibiotic growth promoters in poultry feed, and clove bud is one of the most effective medicinal herbs that has caught the attention of researchers. Aim: This experiment was conducted to evaluate the effects of adding clove bud powder to the broiler chicken's feed on the hematological profile, biochemical parameters, lymphoid organs, and cell-mediated immunity. Method: A total of 360 unsexed chicks (Ross 308) were allotted to three groups. All chicks were raised under the same normal management conditions from 1 day to 6 weeks of age. The first group was fed a basal diet and the other two groups were assigned to add 0.5% and 1.0% of clove bud powder to the basal diet. The studied traits were total leukocyte counts (TLC), differential leukocyte counts (DLC), blood cholesterol level, blood liver enzymes [aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase (ALP) enzymes], the weight of lymphoid organs (bursa of Fabricius and spleen), and cell-mediated immunity. Results: Despite the significant and varied changes (p ≤ 0.05) that resulted from adding clove buds powder to the broiler feed in the second and third weeks, the results at the end of the experiment indicated that there was no negative effect of adding clove powder on the TLC and DLC, as well as the heterophils/lymphocytes ratio. In addition, feeding on a diet containing clove buds powder had no significant effect on the level of cholesterol and liver enzymes in the blood, except for (ALP), which showed a significant increase (p ≤ 0.01) in comparison to the control group. Moreover, the results showed in the second and fifth weeks a significant increase (p ≤ 0.05) in the relative weight of the spleen, but, in general, there were no significant effects at the end of the experiment on the relative weight of the lymphoid organs. Furthermore, the broiler chickens that consumed clove bud powder at a rate of 0.5% showed a highly significant (p ≤ 0.01) cellular immune response. Conclusion: This study concluded that the addition of clove bud powder had no negative effect on leukocyte counts or differentiated leukocyte counts. The addition also raised the spleen weight and improved the level of blood alkane phosphatase activity and cellular immune response in broiler chickens during the growth stages.
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Pollos , Syzygium , Animales , Polvos , Inmunidad Celular , Suplementos DietéticosRESUMEN
Oilseed rape (Brassica napus L.) is an important oilseed crop. We examined the diversity of germplasm expressed at three distinct levels (i.e., morphological, biochemical, and DNA levels). In this study, 150 B. napus L. accessions with three check varieties were provided by Bioresources Conservation Institute. The germplasm was grown in field conditions for data collection of 15 quantitative and nine qualitative agro-morphological traits. The result indicated that for 15 quantitative agro-morphological traits, the highest coefficient of variation was recorded for plant height and days to flowering initiation. For nine qualitative traits, most of the accessions have a spatulate leaf, brown color seeds, yellow flowers, and erect silique attitude. The best adoptable genetically diverse exotic Brassica germplasms were selected, i.e., accessions 24178, 24881, 24199, 24214, 24242, and 24192. Based on biochemical analysis for high oil content and high oleic acid content, chakwal sarsoon and accession 24192 were selected. For high oleic and linoleic acids, accession 24181 performed best, for low erucic acid accessions 24177 and 24195. Based on molecular (SSR) markers, the top 50 selected genotypes were evaluated with 30 SSR markers. The 47 genotypes with three check varieties were clustered in six major groups; the coefficient of similarity ranged between 0.18 and 1.00. Based on SSR data, the germplasms accession 24178 and Abasin were the most diverse genotypes. These genotypes have the capacity and could be used in future breeding programs. High genetic variations were investigated through the SSR among the studied genotypes of Brassica napus L. The present study also concluded that SSR is a better technique for intraspecific genetic diversity. Other modern techniques should be applied such as SNIP for the investigation of a high level of genetic diversity among crop plants in the future.
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In a randomized clinical trial, we compare early neutralizing antibody responses after boosting with bivalent SARS-CoV-2 mRNA vaccines based on either BA.1 or BA.4/BA.5 Omicron spike protein combined with wildtype spike. Responses against SARS-CoV-2 variants exhibited the greatest reduction in titers against currently circulating Omicron subvariants for both bivalent vaccines.
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Vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection wanes over time, requiring updated boosters. In a phase 2, open-label, randomized clinical trial with sequentially enrolled stages at 22 US sites, we assessed safety and immunogenicity of a second boost with monovalent or bivalent variant vaccines from mRNA and protein-based platforms targeting wild-type, Beta, Delta and Omicron BA.1 spike antigens. The primary outcome was pseudovirus neutralization titers at 50% inhibitory dilution (ID50 titers) with 95% confidence intervals against different SARS-CoV-2 strains. The secondary outcome assessed safety by solicited local and systemic adverse events (AEs), unsolicited AEs, serious AEs and AEs of special interest. Boosting with prototype/wild-type vaccines produced numerically lower ID50 titers than any variant-containing vaccine against all variants. Conversely, boosting with a variant vaccine excluding prototype was not associated with decreased neutralization against D614G. Omicron BA.1 or Beta monovalent vaccines were nearly equivalent to Omicron BA.1 + prototype or Beta + prototype bivalent vaccines for neutralization of Beta, Omicron BA.1 and Omicron BA.4/5, although they were lower for contemporaneous Omicron subvariants. Safety was similar across arms and stages and comparable to previous reports. Our study shows that updated vaccines targeting Beta or Omicron BA.1 provide broadly crossprotective neutralizing antibody responses against diverse SARS-CoV-2 variants without sacrificing immunity to the ancestral strain. ClinicalTrials.gov registration: NCT05289037 .
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Vacunas contra la COVID-19 , COVID-19 , Humanos , Vacunas contra la COVID-19/efectos adversos , SARS-CoV-2/genética , COVID-19/prevención & control , Anticuerpos ampliamente neutralizantesRESUMEN
In this brief report, we compare the magnitude and durability of the serologic response of one versus two doses (separated by 56 days) of a variant vaccine (Moderna mRNA-1273 Beta/Omicron BA.1 bivalent vaccine) in adults.
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OBJECTIVES: To measure the magnitude of use of so-called "herbal medications" with or without prescribed drugs and to assess the benefits and adverse effects perceived by herbal users in the Greater Beirut area. METHODS: A sample survey of 480 adults (18-65) in the Greater Beirut (GB) area was conducted over a one-month period in 2009. RESULTS: The estimated weighted prevalence of herbal use in the previous 12 months in GB was 58.9% (56.7-61.2). Most of the 293 users (72.4%) believed that their use had been of no benefit, but 70% thought use was relatively safe. Of users, 53% were concomitantly using conventional drugs for a chronic condition yet only 45% had thought of informing their physician about herbal use. Among the "concomitant users" 60% had suffered some form of adverse effects. CONCLUSIONS: There is a relatively high prevalence of herbal medicine use in Greater Beirut, with an important rate of self-reported adverse effects, especially among those who suffer chronic conditions, and little exchange of information on this between patients and doctors. Data indicate the need to educate patients about realities associated with abusive use, expected benefits and potential drug-herb interaction. Patients on chronic medications should not be left to actually experience adverse effects in order to discover that herbal medicines are not always effective or innocuous.
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Fitoterapia/estadística & datos numéricos , Adolescente , Adulto , Anciano , Femenino , Amigos , Humanos , Líbano , Masculino , Medios de Comunicación de Masas , Persona de Mediana Edad , Fitoterapia/efectos adversos , Adulto JovenRESUMEN
Background Osteoporosis is one of the major worldwide health concerns and carries medical, social, and financial impacts due to its significant morbidity and mortality. The aim of this study was to explore the practice of family physicians in osteoporosis management in older female patients. Method This study was performed in a cross-sectional manner. Data, including patient and disease characteristics and management practices, were obtained from the electronic patient chart for female patients aged 60 years and older who were followed in family medicine clinics at King Abdulaziz Medical City, Riyadh, Saudi Arabia, during the period from January 1, 2018, to December 31, 2020. Management was checked and evaluated against osteoporosis management guidelines. Results In 42 patients out of 250, an osteoporosis diagnosis was missed. Among the 208 charts that were reviewed, the mean patient age was 72.06 years, and the mean duration of the disease according to the initial dual-energy X-ray absorptiometry (DXA) scan was 3.68 years. Laboratory tests were performed for only about half of the patients. Vitamin D was given only to 54.3% while calcium supplements were given only to 53.4%. Almost one-third of the patients have not been prescribed any antiosteoporosis medications. Conclusion The current study documented that older females with osteoporosis were not well-managed in the investigated family medicine settings. Continuous professional development activities and periodic practice reviews are suggested to improve this situation.
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Edema resulting from the initiation of insulin therapy or intensification of glycemic control is a rare and under-recognized complication. In this report, we present a case of a 46-year-old patient with insulin-dependent diabetes mellitus (IDDM) who avoided insulin treatment due to associated peripheral edema. Though rare, this phenomenon is typically seen in patients with elevated glucose levels who are initiated on insulin treatment, resulting in rapid correction and tight control of glucose levels. The diagnosis of insulin-induced edema is made after other causes of acute edema are ruled out. Furthermore, in this case report, we will also discuss the postulated mechanisms for the edema-causing property of insulin.
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Background: Cloves are aromatic spices containing diverse chemically active substances with biological properties. They have also been used in traditional medicine. Aim: This experiment was conducted to evaluate the effect of clove bud powder (CBP) dietary administration on the performance and jejunum morphology of the broiler chickens. Methods: A total of 360 1-day-old chicks (Ross 308) were distributed according to a completely randomized design on 3 experimental groups according to CBP% in feed (0.0%, 0.5%, and 1.0%), with 6 replicates for each treatment group. The studied traits included body weight, daily weight gain, daily feed consumption, feed conversion ratio, mortality%, European broiler index (EBI), villus height, crypt depth, and villus height/crypt depth ratio. Results: The broilers final body weight, daily weight gain, and daily feed consumption reduced significantly (p ≤ 0.01) in groups consuming different percentages of CBP, and a significant increase (p < 0.05) in feed conversion ratio was noted in the CBP groups. Adding CBP to feed caused a significant decrease (p < 0.05) in the EBI. However, CBP increased (p ≤ 0.01) villus height and villus height/crypt depth ratio (h/c ratio) compared to the control group. On the other hand, the results showed that there were no significant differences (p > 0.05) between treatment groups in mortality% and crypt depth. Conclusion: This study concluded that the addition of CBP had a negative effect on daily feed consumption, daily body weight gain, final body weight, feed conversion ratio, and EBI at a dose used in this study. But it improved intestinal morphology.
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Suplementos Dietéticos , Syzygium , Animales , Alimentación Animal/análisis , Fenómenos Fisiológicos Nutricionales de los Animales , Peso Corporal , Pollos , Dieta/veterinaria , Yeyuno , Polvos , Aumento de PesoRESUMEN
ETNOPHARMACOLOGICAL RELEVANCE: Common sage (Salvia officinalis L., Lamiaceae), a medicinal plant of Mediterranean origin, has been traditionally applied in cases of excessive sweating, and in menopausal complaints, including hot flushes. AIM OF THE STUDY: This study aims to study the possible estrogenic effect of the aerial parts of S. officinalis ethanolic extract in immature ovariectomized female rats. MATERIALS AND METHODS: The ethanolic extract was subjected to qualitative and quantitative HPLC analysis and phytochemical isolation. The estrogenic activity of S. officinalis ethanolic extract at oral doses of 50, 100 and 200 mg/kg b.wt. and its isolated ferulic acid at a dose of 50 mg/kg b.wt. for a week, was assessed on ovariectomized immature Wistar rats. The experiment was confirmed by luteinizing hormone (LH) and follicle stimulating hormone (FSH) serum levels determination, a histopathological examination and a histomorphometrical study. RESULTS: HPLC/PDA analysis revealed fourteen phenolic compounds the major constituents were methyl rosmarinate (24.86 mg/100 g) and ferulic acid (6.06 mg/100 g) together with five flavonoids where the major constituents were rutin, naringenin and quercetin. Two compounds were isolated from the polar fraction and identified as methyl rosmarinate (1) and ferulic acid (2). Oral administration of sage ethanolic extract and ferulic acid revealed a significant increase in the uterine weight compared to ovariectomized control rats. Moreover, S. officinalis and ferulic acid showed different phases of estrus cycle denoting estrogenic activity, and significantly decreased the serum levels of FSH and LH. CONCLUSION: From these results it could be concluded that S. officinalis ethanolic extract and its content of ferulic acid could be useful as a safe natural source for estrogenic activity, supporting its traditional use to improve postmenopausal symptoms.
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Estrógenos , Menopausia/efectos de los fármacos , Extractos Vegetales , Animales , Antioxidantes/farmacología , Ácidos Cumáricos/farmacología , Relación Dosis-Respuesta a Droga , Estrógenos/química , Estrógenos/farmacología , Femenino , Flavonoides/farmacología , Ovariectomía/métodos , Fitoquímicos/química , Fitoquímicos/farmacología , Componentes Aéreos de las Plantas , Extractos Vegetales/química , Extractos Vegetales/farmacología , Ratas , Ratas Wistar , Salvia officinalisRESUMEN
The chr12q24.13 locus encoding OAS1-OAS3 antiviral proteins has been associated with coronavirus disease 2019 (COVID-19) susceptibility. Here, we report genetic, functional and clinical insights into this locus in relation to COVID-19 severity. In our analysis of patients of European (n = 2,249) and African (n = 835) ancestries with hospitalized versus nonhospitalized COVID-19, the risk of hospitalized disease was associated with a common OAS1 haplotype, which was also associated with reduced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clearance in a clinical trial with pegIFN-λ1. Bioinformatic analyses and in vitro studies reveal the functional contribution of two associated OAS1 exonic variants comprising the risk haplotype. Derived human-specific alleles rs10774671-A and rs1131454 -A decrease OAS1 protein abundance through allele-specific regulation of splicing and nonsense-mediated decay (NMD). We conclude that decreased OAS1 expression due to a common haplotype contributes to COVID-19 severity. Our results provide insight into molecular mechanisms through which early treatment with interferons could accelerate SARS-CoV-2 clearance and mitigate against severe COVID-19.
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COVID-19 , 2',5'-Oligoadenilato Sintetasa/genética , 2',5'-Oligoadenilato Sintetasa/metabolismo , Alelos , COVID-19/genética , Hospitalización , Humanos , SARS-CoV-2/genéticaRESUMEN
Background: Protection from SARS-CoV-2 vaccines wanes over time and is compounded by emerging variants including Omicron subvariants. This study evaluated safety and immunogenicity of SARS-CoV-2 variant vaccines. Methods: This phase 2 open-label, randomized trial enrolled healthy adults previously vaccinated with a SARS-CoV-2 primary series and a single boost. Eligible participants were randomized to one of six Moderna COVID19 mRNA vaccine arms (50µg dose): Prototype (mRNA-1273), Omicron BA.1+Beta (1 or 2 doses), Omicron BA.1+Delta, Omicron BA.1 monovalent, and Omicron BA.1+Prototype. Neutralization antibody titers (ID 50 ) were assessed for D614G, Delta, Beta and Omicron BA.1 variants and Omicron BA.2.12.1 and BA.4/BA.5 subvariants 15 days after vaccination. Results: From March 30 to May 6, 2022, 597 participants were randomized and vaccinated. Median age was 53 years, and 20% had a prior SARS-CoV-2 infection. All vaccines were safe and well-tolerated. Day 15 geometric mean titers (GMT) against D614G were similar across arms and ages, and higher with prior infection. For uninfected participants, Day 15 Omicron BA.1 GMTs were similar across Omicron-containing vaccine arms (3724-4561) and higher than Prototype (1,997 [95%CI:1,482-2,692]). The Omicron BA.1 monovalent and Omicron BA.1+Prototype vaccines induced a geometric mean ratio (GMR) to Prototype for Omicron BA.1 of 2.03 (97.5%CI:1.37-3.00) and 1.56 (97.5%CI:1.06-2.31), respectively. A subset of samples from uninfected participants in four arms were also tested in a different laboratory at Day 15 for neutralizing antibody titers to D614G and Omicron subvariants BA.1, BA.2.12.2 and BA.4/BA.5. Omicron BA.4/BA.5 GMTs were approximately one third BA.1 GMTs (Prototype 517 [95%CI:324-826] vs. 1503 [95%CI:949-2381]; Omicron BA.1+Beta 628 [95%CI:367-1,074] vs. 2125 [95%CI:1139-3965]; Omicron BA.1+Delta 765 [95%CI:443-1,322] vs. 2242 [95%CI:1218-4128] and Omicron BA.1+Prototype 635 [95%CI:447-903] vs. 1972 [95%CI:1337-2907). Conclusions: Higher Omicron BA.1 titers were observed with Omicron-containing vaccines compared to Prototype vaccine and titers against Omicron BA.4/BA.5 were lower than against BA.1 for all candidate vaccines. Clinicaltrialsgov: NCT05289037.