Local Adverse Reactions Research Articles

Effectiveness and safety of biological therapy in patients with severe asthma in a real clinical practice

To assess effectiveness and safety of biological therapy in patients with severe asthma during 5 yr follow-up. We recruited 129 adult outpatients (29% males) aged 18-81 yrs with severe asthma were followed up during 5 yrs and were examined for every 3-6 months. Eighty five patients were treated by conventional therapy (ICS/LABA ± tiotropium, montelukast, OCS) only and 44 pts additionally received biologicals (оmalizumab - 9 pts, мepolizumab - 8 pts, benralizumab - 11 pts, dupilumab - 16 pts). Pulmonary function tests were measured by dry spirometer (2120, Vitalograph Ltd., UK). Eosinophil count in blood was assessed by automatic haemoanalyser. Fraction of exhaled nitric oxide was measured by a chemiluminescence analyzer (LR4100; Logan Research, UK). Asthma control and quality of life were assessed by using Russian versions of ACQ-5 and SGRQ. The use of biologicals led to a more significant reduction of exacerbations and OCS use, improvement of lung function, asthma control and quality of life, decrease of eosinophil and fraction of exhaled nitric oxide than conventional therapy of severe asthma (p<0.05). Systemic side effects were not registered, frequency of local adverse reactions (edema, hyperemia and itching at injection site) was 14%. Long-term use of biologicals added to conventional therapy in patients with severe asthma is characterized by high effectiveness and favorable safety profile.

Immunogenicity and safety of an ORF7-deficient skin-attenuated and neuro-attenuated live vaccine for varicella: a randomised, double-blind, controlled, phase 2a trial

The Oka varicella vaccine strain remains neurovirulent and can establish lifelong latent infection, raising safety concerns about vaccine-related herpes zoster. In this study, we aimed to evaluate the immunogenicity and safety of a skin-attenuated and neuro-attenuated varicella vaccine candidate (v7D vaccine). We did this randomised, double-blind, controlled, phase 2a clinical trial in Jiangsu, China. Healthy children aged 3-12 years with no history of varicella infection or vaccination were enrolled and randomly assigned (1:1:1:1) to receive a single subcutaneous injection of the v7D vaccine at 3·3 log10 plaque forming units (PFU; low-dose v7D group), 3·9 log10 PFU (medium-dose v7D group), and 4·2 log10 PFU (high-dose v7D group), or the positive control varicella vaccine (vOka vaccine group). All the participants, laboratory personnel, and investigators other than the vaccine preparation and management staff were masked to the vaccine allocation. The primary outcome was assessment of the geometric mean titres (GMTs) and seroconversion rates of anti-varicella zoster virus immunoglobulin G (IgG) induced by different dose groups of v7D vaccine at 0, 42, 60, and 90 days after vaccination in the per-protocol set for humoral immune response analysis. Safety was a secondary outcome, focusing on adverse events within 42 days post-vaccination, and serious adverse events within 6 months after vaccination. This study was registered on Chinese Clinical Trial Registry, ChiCTR2000034434. On Aug 18-21, 2020, 842 eligible volunteers were enrolled and randomly assigned treatment. After three participants withdrew, 839 received a low dose (n=211), middle dose (n=210), or high dose (n=210) of v7D vaccine, or the vOka vaccine (n=208). In the per-protocol set for humoral immune response analysis, the anti-varicella zoster virus IgG antibody response was highest at day 90. At day 90, the seroconversion rates of the low-dose, medium-dose, and high-dose groups of v7D vaccine and the positive control vOka vaccine group were 100·0% (95% CI 95·8-100·0; 87 of 87 participants), 98·9% (93·8-100·0; 87 of 88 participants), 97·8% (92·4-99·7; 91 of 93 participants), and 96·4% (89·8-99·2; 80 of 83 participants), respectively; the GMTs corresponded to values of 30·8 (95% CI 26·2-36·0), 31·3 (26·7-36·6), 28·2 (23·9-33·2), and 38·5 (31·7-46·7). The v7D vaccine, at low dose and medium dose, elicited a humoral immune response similar to that of the vOka vaccine. However, the high-dose v7D vaccine induced a marginally lower GMT compared with the vOka vaccine at day 90 (p=0·027). In the per-protocol set, the three dose groups of the v7D vaccine induced a similar humoral immune response at each timepoint, with no statistically significant differences. The incidence of adverse reactions in the low-dose, medium-dose, and high-dose groups of v7D vaccine was significantly lower than that in the vOka vaccine group (17% [35 of 211 participants], 20% [41 of 210 participants], and 13% [27 of 210 participants] vs 24% [50 of 208 participants], respectively; p=0·025), especially local adverse reactions (10% [22 of 211 participants], 14% [30 of 210 participants] and 9% [18 of 210 participants] vs 18% [38 of 208 participants], respectively; p=0·016). None of the serious adverse events were vaccine related. The three dose groups of the candidate v7D vaccine exhibit similar humoral immunogenicity to the vOka vaccine and are well tolerated. These findings encourage further investigations on two-dose vaccination schedules, efficacy, and the potential safety benefit of v7D vaccine in the future. The National Natural Science Foundation of China, CAMS Innovation Fund for Medical Sciences, the Fundamental Research Funds for the Central Universities, and Beijing Wantai. For the Chinese translation of the abstract see Supplementary Materials section.

Background of Patients Who Received Two Doses of Adjuvanted Herpes Zoster Vaccine at a Clinic and Comparative Evaluation of Local and Systemic Adverse Reactions

Background of Patients Who Received Two Doses of Adjuvanted Herpes Zoster Vaccine at a Clinic and Comparative Evaluation of Local and Systemic Adverse Reactions

Therapy of netakimab in nail psoriasis

Introduction. The nail psoriasis severity does not always correspond to the skin process intensity, but often correlates with a more severe, prolonged and aggressive course of the disease.Materials and methods. 48 adult patients (n = 48) with nail psoriasis were under observation. The severity of the psoriatic lesion of the nails was determined using the NAPSI index (Nail Psoriasis Severity Index). The assessment was carried out before the start of treatment, in the first week, and then every 4 weeks up to and including 52 weeks. The Dermatological Quality of Life Index (DLQI) were determined by questionnaires before the start of treatment, at the 12th and 52nd weeks. All patients on an outpatient basis received netakimab monotherapy at a dose of 120 mg in the form of two subcutaneous injections of 1 ml (60 mg) of the drug, each administered once a week at weeks 0, 1 and 2, then 1 time every 4 weeks. The total duration of treatment for each patient was 52 weeks. The safety of netakimab was evaluated based on the development of adverse events and local reactions to the administration of the drug.Results. The results of the study for 52 weeks showed high efficacy of netakimab. Average NAPSI score improved – 33.1% by the week 12 of treatment and – 72.3% by the week 52 compared to baseline, the quality of their life improved. During the 52 weeks of the study, there were no cases of early withdrawal due to adverse events and cases of serious adverse events.Conclusion. Based on the study results we recommend netakimab for medical use among patients with moderate and severe nail psoriasis.

Subcutaneous sodium valproate in palliative care: A systematic review

Background: Seizures are an important palliative symptom, the management of which can be complicated by patients’ capacity to swallow oral medications. In this setting, and the wish to avoid intravenous access, subcutaneous infusions may be employed. Options for antiseizure medications that can be provided subcutaneously may be limited. Subcutaneous sodium valproate may be an additional management strategy. Aim: To evaluate the published experience of subcutaneous valproate use in palliative care, namely with respect to effectiveness and tolerability. Design: A systematic review was registered (PROSPERO CRD42023453427), conducted and reported according to PRISMA reporting guidelines. Data sources: The databases PubMed, EMBASE and Scopus were searched for publications until August 11, 2023. Results: The searches returned 429 results, of which six fulfilled inclusion criteria. Case series were the most common study design, and most studies included <10 individuals who received subcutaneous sodium valproate. There were three studies that presented results on the utility of subcutaneous sodium valproate for seizure control, which described it to be an effective strategy. One study also described it as an effective treatment for neuropathic pain. The doses were often based on presumed 1:1 oral to subcutaneous conversion ratios. Only one study described a local site adverse reaction, which resolved with a change of administration site. Conclusions: There are limited data on the use of subcutaneous sodium valproate in palliative care. However, palliative symptoms for which subcutaneous sodium valproate have been used successfully are seizures and neuropathic pain. The available data have described few adverse effects, supporting its use with an appropriate degree of caution.

A phase II clinical trial of a Vi-DT typhoid conjugate vaccine in healthy Indonesian adolescents and adults: one-month evaluation of safety and immunogenicity

BackgroundTyphoid fever is commonly found until today, especially in developing countries. It has fatal complications and measures must be taken to reduce the incidence of typhoid. Vaccinations are a key factor in prevention. This is a phase II randomized observer-blind clinical trial on a novel Vi-DT conjugate vaccine on 200 subjects 12 to 40 years of age.MethodsSubjects were screened for eligibility after which a blood sample was taken and one dose of vaccine was administered. Investigational vaccine used was Vi-DT and control was Vi-PS. Twenty-eight days after vaccination, subjects visited for providing blood sample to assess immunogenicity and were asked about local and systemic adverse reactions that occurred in the first 28 days.ResultsSubjects had minor adverse reactions. Pain was the most common local reaction. Muscle pain was the most common systemic reaction. There were no serious adverse events up to 28 days post vaccination. Seroconversion rates were 100% in the Vi-DT group and 95.96% in the Vi-PS group. Post vaccination GMTs were increased in both groups but it was significantly higher in the Vi-DT group (p < 0.001).ConclusionsVi-DT typhoid conjugate vaccine is safe and immunogenic in healthy Indonesian subjects 12 to 40 years.Trial registrationApproved by ClinicalTrials.gov. Clinical trial registration number: NCT03460405. Registered on 09/03/2018. URL: https://clinicaltrials.gov/ct2/show/NCT03460405.

Assessment of pharmacovigilance guidelines in the Southern African Development Community: A document review.

Lack of harmonization in pharmacovigilance (PV) practice in resource-limited states in Africa has led to differentiation and marginalization, thus creating an environment where weak or absent PV systems may benefit from regional guidelines. To compare the PV guidelines of Southern African Development Community (SADC) member states to international guidelines and identify areas for improvement for aligning PV practice within the SADC region. We utilized a 73-item checklist to assess the PV guidelines of the SADC member states. Checklist parameters were rated using binary scoring. Only seven (Botswana, Mauritius, Namibia, South Africa, Tanzania, Zambia, and Zimbabwe) of the 16 SADC member states had guidelines to assess. Of these, only four had supporting legislation. All seven national medicines regulatory authorities (NMRA)'s guidelines required reporting of local serious adverse drug reactions (ADRs). Four NMRAs implemented device vigilance; none specified submission timelines for ADRs associated with substandard or falsified medicines. Only three NMRAs required electronic transmission of individual case safety reports in the E2B format. Five NMRAs mandated safety monitoring during interventional clinical trials. Five NMRAs required aggregate reporting through periodic safety update reports. Only two NMRAs required submission of the development safety update report. Regarding risk management, four NMRAs required notification of actions taken by foreign NMRAs and four NMRAs expected to review Dear Healthcare Professional Letters before distribution by the marketing authorization holder. Areas for improvement of guidelines to establish common process standards and allow for synchronized submissions of comparable data to SADC NMRAs are provided.

Safety and immunogenicity of conjugate vaccine for typhoid (Vi-DT): Finding from an observer-blind, active-controlled, randomized, non-inferiority, phase III clinical trial among healthy volunteers

ABSTRACT Typhoid fever is a significant public health concern with most of the sufferers between 15 and 25 y of age in Nepal. We undertook this study to demonstrate Vi polysaccharide conjugated with diphtheria toxoid (Vi-DT) conjugate vaccine which is non-inferior to Typbar typhoid conjugate vaccine, a Vi polysaccharide vaccine conjugated with tetanus toxoid (Vi-TT) with a focus on the adult population from Dhulikhel Hospital which was one of the total four sites in Nepal. In this study, we assigned the eligible participants in 1:1:1:1 ratio by block randomization, and stratified into three age groups (6 months to less than 2 y, 2 y to less than 18 y, and 18 y to 45 y), allotted to Group A, B, C, and D. Group A, B, and C received 25 μg (0.5 mL) of Vi-DT study vaccine and participants in Group D received 25 μg (0.5 mL) Vi-TT vaccine. We descriptively analyzed safety in all the participants receiving one dose of the investigational vaccine. The anti-Vi-IgG seroconversion rate in Vi-DT recipients was 99.71% (97.5% CI 98.04–99.96; 344 of 345 participants) and 99.13% (94.27–99.87; 114 of 115) in Vi-TT recipients which indicates that Vi-DT vaccine is non-inferior to Vi-TT vaccine. In safety aspect, 16.81% of total subject had at least one solicited adverse reaction and 22.61% of the Vi-TT participants experienced at least one solicited adverse reaction with most of them being local adverse reactions. None of the enrolled participants reported serious adverse events. Our study shows that a single dose of the Vi-DT vaccine is immunogenic, safe to administer and non-inferior to the Vi-TT vaccine four weeks after vaccination.

Safety assessments of recombinant DTaP vaccines developed in South Korea.

Pertussis bacteria have many pathogenic and virulent antigens and severe adverse reactions have occurred when using inactivated whole-cell pertussis vaccines. Therefore, inactivated acellular pertussis (aP) vaccines and genetically detoxified recombinant pertussis (rP) vaccines are being developed. The aim of this study was to assess the safety profile of a novel rP vaccine under development in comparison to commercial diphtheria-tetanus-acellular pertussis (DTaP) vaccines. The two positive control DTaP vaccines (two- and tri-components aP vaccines) and two experimental recombinant DTaP (rDTaP) vaccine (two- and tri-components aP vaccines adsorbed to either aluminum hydroxide or purified oat beta-glucan) were used. Temperature histamine sensitization test (HIST), indirect Chinese hamster ovary (CHO) cell cluster assay, mouse-weight-gain (MWG) test, leukocytosis promoting (LP) test, and intramuscular inflammatory cytokine assay of the injection site performed for safety assessments. HIST results showed absence of residual pertussis toxin (PTx) in both control and experimental DTaP vaccine groups, whereas in groups immunized with tri-components vaccines, the experimental tri-components rDTaP absorbed to alum showed an ultra-small amount of 0.0066 IU/mL. CHO cell clustering was observed from 4 IU/mL in all groups. LP tests showed that neutrophils and lymphocytes were in the normal range in all groups immunized with the two components vaccine. However, in the tri-components control DTaP vaccine group, as well as two- and tri-components rDTaP with beta-glucan group, a higher monocyte count was observed 3 days after vaccination, although less than 2 times the normal range. In the MWG test, both groups showed changes less than 20% in body temperature and body weight before the after the final immunizations. Inflammatory cytokines within the muscle at the injection site on day 3 after intramuscular injection revealed no significant response in all groups. There were no findings associated with residual PTx, and no significant differences in both local and systemic adverse reactions in the novel rDTaP vaccine compared to existing available DTaP vaccines. The results suggest that the novel rDTaP vaccine is safe.

Anafilaktički šok izazvan subkutanom imunoterapijom alergenom Ambrosia elatior - prikaz slučaja

Introduction: Sensitization to ragweed pollen can lead to symptoms of allergic rhinitis, conjunctivitis, and allergic asthma. Allergen immunotherapy (AIT) is an immunomodulatory therapeutic procedure that, in addition to short-term curative effect (reduction of disease symptoms), also has a long-term preventive effect (preventing the progression of allergic rhinitis into allergic asthma and/or preventing the development of a more severe form of the disease). The two main AIT administration modalities used in clinical practice are subcutaneous allergen immunotherapy (SCIT) and sublingual allergen immunotherapy (SLIT). Both modalities are equally effective in reducing disease symptoms, but the use of SCIT is associated with a higher risk of local and systemic adverse reactions. Case report: A patient who developed a clinical picture of anaphylactic shock during the induction phase of SCIT with Ambrosia elatior pollen extract is presented in this article. The clinical course is described as well as the quick and effective therapeutic management of this life-threatening condition. Conclusion: When properly dosed, in a medical facility and under medical supervision, SCIT with Ambrosia elatior is a very safe and well-tolerated treatment option for allergic rhinitis. Local reactions at the site of subcutaneous administration occur more often than systemic adverse reactions. Anaphylactic shock is the most severe form of a systemic allergic reaction that affects multiple organ systems and can end in death, usually due to airway obstruction and cardiovascular collapse. It is necessary to educate the medical staff as well as the patients regarding the proper treatment of this difficult condition. Based on the assessment of risk factors in each patient, severe reactions to SCIT can be predicted and avoided with appropriate precautions and prophylactic measures. Future innovations in AIT are expected to further improve the efficacy and safety of this form of treatment for allergic diseases.

Infrared thermography used to detect local adverse reactions induced by reproductive vaccine adjuvants in Holstein heifers

Infrared thermography used to detect local adverse reactions induced by reproductive vaccine adjuvants in Holstein heifers

Efficacy of Limosilactobacillus fermentum in the management of vulvovaginal candidiasis: comparative analysis with topical miconazole in a single-blind randomized clinical trial.

Vulvovaginal candidiasis (VVC) significantly impacts women's quality of life and often shows a high recurrence rate despite conventional antifungal therapies. This study evaluates the efficacy of Limosilactobacillus fermentum (LF5), a probiotic, as an alternative treatment option to conventional miconazole therapy in managing VVC. The randomized, single-blind clinical trial involved 100 premenopausal women diagnosed with VVC. Participants were assigned to either a vaginal capsule containing LF5 probiotic strain or miconazole. Treatments were administered once daily for three consecutive days. Microbiological eradication of Candida spp. and recurrence rates were assessed at 30 days post-treatment. The trial was registered with the Italian Ministry of Health. Both treatments achieved a high rate of microbiological eradication of Candida spp. within the three-day treatment period (96% for LF5 and 94% for miconazole). Recurrence rates within 2 weeks post-treatment were low and similar between the groups (10% for LF5 and 17% for miconazole). LF5 was found to have a significantly lower incidence of local adverse reactions compared to miconazole (4 vs. 12%). LF5 presents a viable alternative to miconazole for the treatment of VVC, offering comparable efficacy with fewer side effects. The results suggest that probiotic treatments can potentially enhance patient compliance and quality of life by reducing adverse reactions and recurrence rates. Further research is needed to confirm these findings in larger and more diverse populations.

Nursing Effects of Modified Intramuscular Injection Technique in Syphilis Treatment with Benzathine Penicillin

Nursing Effects of Modified Intramuscular Injection Technique in Syphilis Treatment with Benzathine Penicillin

Efficacy and Safety of an mRNA-Based RSV PreF Vaccine in Older Adults

BackgroundRespiratory syncytial virus (RSV) can cause substantial morbidity and mortality among older adults. An mRNA-based RSV vaccine, mRNA-1345, encoding the stabilized RSV prefusion F glycoprotein, is under clinical investigation.MethodsIn this ongoing, randomized, double-blind, placebo-controlled, phase 2–3 trial, we randomly assigned, in a 1:1 ratio, adults 60 years of age or older to receive one dose of mRNA-1345 (50 μg) or placebo. The two primary efficacy end points were the prevention of RSV-associated lower respiratory tract disease with at least two signs or symptoms and with at least three signs or symptoms. A key secondary efficacy end point was the prevention of RSV-associated acute respiratory disease. Safety was also assessed.ResultsOverall, 35,541 participants were assigned to receive the mRNA-1345 vaccine (17,793 participants) or placebo (17,748). The median follow-up was 112 days (range, 1 to 379). The primary analyses were conducted when at least 50% of the anticipated cases of RSV-associated lower respiratory tract disease had occurred. Vaccine efficacy was 83.7% (95.88% confidence interval [CI], 66.0 to 92.2) against RSV-associated lower respiratory tract disease with at least two signs or symptoms and 82.4% (96.36% CI, 34.8 to 95.3) against the disease with at least three signs or symptoms. Vaccine efficacy was 68.4% (95% CI, 50.9 to 79.7) against RSV-associated acute respiratory disease. Protection was observed against both RSV subtypes (A and B) and was generally consistent across subgroups defined according to age and coexisting conditions. Participants in the mRNA-1345 group had a higher incidence than those in the placebo group of solicited local adverse reactions (58.7% vs. 16.2%) and of systemic adverse reactions (47.7% vs. 32.9%); most reactions were mild to moderate in severity and were transient. Serious adverse events occurred in 2.8% of the participants in each trial group.ConclusionsA single dose of the mRNA-1345 vaccine resulted in no evident safety concerns and led to a lower incidence of RSV-associated lower respiratory tract disease and of RSV-associated acute respiratory disease than placebo among adults 60 years of age or older. (Funded by Moderna; ConquerRSV ClinicalTrials.gov number, NCT05127434.)

Single and repeat-dose toxicity and local tolerance assessment of newly developed oil emulsion adjuvant formulations for veterinary purposes

Adjuvants are components of vaccines that boost the intensity, duration, and breadth of the immune response. Insight into the mechanisms responsible for the immunotoxicity of both local and systemic adverse reactions following the use of adjuvants has been gained through research over the past twenty years. In the present study, single and repeated-dose toxicity and local tolerance of newly developed Water-in-Oil (W/O) and Water-in-Oil-in-Water (W/O/W) Emulsion adjuvants (Coralvac RZ 528, Coralvac RZ 506, Coralvac AT 318, Coralvac AT 318 SIS and Coralvac 252) by Coral Biotechnology Industry and Trade Incorporated Company were demonstrated after intramuscular injection in mice. In both toxicity studies, no adverse reactions such as death, general appearance, behavior, or weight loss were observed in the mice in the experimental groups. The results indicate that clinical chemistry parameters demonstrated normal function of the major organs and no irreversible damage to the mice in all adjuvant groups compared to the control group. In histopathologic investigation of single dose toxicity study, inflammation, edema, and large amounts of lipid droplets were observed on the 7th day in all experimental groups. On the 14th day, when the control group and the experimental groups were compared, it was seen that inflammation and edema had decreased considerably. Similarly, repeated dose toxicity study showed mild inflammation and edema in the control group, while quite widespread and severe inflammation, edema, and diffuse lipid droplets of varying sizes were observed in all adjuvant groups compared to the control group. These observations would be useful for the future development of oil-based adjuvants and their use in veterinary inactive vaccines.

Corticosteroid injections for non-spinal musculoskeletal conditions: Consideration of local and systemic adverse drug reactions and side effects

Following specialist training, physiotherapists in some countries, such as the United Kingdom and Norway perform landmark, and ultrasound guided, soft tissue and joint injections for a wide range of musculoskeletal conditions. Whether they inject or not, physiotherapists may wish to recommend injections, and people requiring care commonly seek physiotherapist’s opinions on injection therapy. Globally, there has been a substantial increase in the use of corticosteroid injections to treat musculoskeletal conditions. Those performing injections or providing advice need be cognisant of the possible harms of the procedures and communicate this information sensitively to those considering the procedures. This review synthesises evidence for local and systemic adverse reactions and side effects related to corticosteroid injections in the treatment of non-spinal musculoskeletal conditions. Multiple databases including PubMed, Medline, PEDro, Cinahl were searched, and all levels of evidence were included if they added to the review. Serious adverse events appear to be rare, possibly in part, due to under-reporting of side effects. Where available, suggestions for minimising risk and aftercare have been made. As substantial gaps in the evidence were found, areas for further research are suggested and a decision-making tool is included to facilitate whether to proceed to injection, proceed with precaution or no injection.

2655. Phase 1 Safety and Immunogenicity Results of Two Investigational mRNA Vaccines, mRNA-1345, a Respiratory Syncytial Virus Vaccine, and mRNA-1653, a Human Metapneumovirus and Parainfluenza Virus Type 3 Combination Vaccine in Seropositive Young Children

Abstract Background Respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and parainfluenza virus type 3 (PIV3) are common respiratory illnesses in children. Two investigational vaccines, mRNA-1345, encoding the RSV prefusion stabilized F (preF) glycoprotein, and mRNA-1653, encoding the hMPV and PIV3 F glycoproteins, are in clinical trials. Methods Two phase 1, randomized, observer-blind, placebo-controlled trials in children aged 12-59 months assessed safety and immunogenicity of mRNA-1345 (NCT04528719) and mRNA-1653 (NCT04144348). In the mRNA-1345 trial, RSV-seropositive children (N=46) were randomized to receive 3 doses of mRNA-1345 (15 µg or 30 µg) or placebo 2 months apart. In the mRNA-1653 trial, hMPV- and PIV3-seropositive children (N=27) were randomized to receive 2 doses of mRNA-1653 (10 µg or 30 µg) or placebo 2 months apart. Interim data through Month (M) 5 for mRNA-1345 and M3 for mRNA-1653 are reported. Results mRNA-1345 and mRNA-1653 were well-tolerated. The most frequently reported solicited local adverse reaction (AR) was tenderness at injection site (mRNA-1345, 35.7%-71.4%; placebo, 26.7%-42.9% and mRNA-1653, 44.4%-60.0%; placebo, 12.5%-30.0%); solicited systemic ARs (mRNA-1345, 12.5%-53.3%; placebo, 33.3%-50.0% and mRNA-1653, 33.3%-55.6%; placebo, 12.5%-60.0%) were mostly grade 1/2. One mRNA-1345 injection boosted RSV neutralizing antibody (nAb) titers (geometric mean fold rise [GMFR] over baseline: RSV-A=18.9-34.9; RSV-B=7.2-14.3) and RSV preF and postF binding antibody (bAb) concentrations (GMFR: preF=13.9-26.5; postF=9.3-16.0); additional injections did not further elevate antibody levels (Fig 1A and 2A). One mRNA-1653 injection boosted hMPV and PIV3 nAb titers (GMFR over baseline: hMPV-A=2.9-6.1; hMPV-B=6.2-13.2; PIV3=2.8-3.0) and preF and postF bAb concentrations (GMFR: hMPV preF=5.3-6.1; postF=4.6-6.5 and PIV3 preF=13.9-14.2; postF=11.0-12.1); a second injection did not further increase antibody levels (Fig 1B,C and 2B,C). In both trials, bAb responses were generally preF biased. Conclusion In seropositive children aged 12-59 months, mRNA-1345 and mRNA-1653 were well-tolerated and boosted RSV and hMPV plus PIV3 antibodies, respectively, supporting their continued development and that of a combination RSV and hMPV vaccine. Disclosures Matthew D. Snape, MBBS, MD, FRCPCH, FPM, FMedSci, Moderna Biotech UK, Inc.,: Employee|Moderna Biotech UK, Inc.,: Stocks/Bonds Sabine Schnyder Ghamloush, MD, Moderna, Inc.: Employee|Moderna, Inc.: Stocks/Bonds Grace L. Chen, MD, MPH, Moderna, Inc.: Employee|Moderna, Inc.: Stocks/Bonds Rakesh Dhar, MD, Moderna, Inc.: Employee|Moderna, Inc.: Stocks/Bonds Runa Mithani, PharmD, Moderna, Inc: Employee|Moderna, Inc: Stocks/Bonds Vinicius Righi, PharmD, MBA, Moderna, Inc.: Employee|Moderna, Inc.: Stocks/Bonds Louie Morsy, BS, Moderna, Inc.: Employee|Moderna, Inc.: Stocks/Bonds Archana Kapoor, PhD, Moderna, Inc.: Employee|Moderna, Inc.: Stocks/Bonds Bethany Girard, Ph.D., Moderna, Inc.: salary|Moderna, Inc.: Stocks/Bonds Laila El Asmar, PhD, Moderna, Inc.: Employee|Moderna, Inc.: Stocks/Bonds Christine A. Shaw, PhD, Moderna, Inc.: Employee|Moderna, Inc.: Stocks/Bonds

5-aminolevulinic acid photodynamic therapy using 560-1200 nm followed by 420-1200 nm broadband light in the treatment of moderate-to-severe acne

BackgroundModerate-to-severe acne vulgaris, which is a chronic inflammatory skin disease, seriously impacts millions of people. However, traditional therapies may cause severe adverse reactions that are unacceptable to many patients, thus limiting the further application of these therapies. Novel therapeutic approaches to effectively treat moderate-to-severe acne vulgaris with minimal adverse reactions are urgently needed. In this retrospective study, we investigated the efficacy and adverse reactions of photodynamic therapy (PDT) using 560–1200 nm followed by 420–1200 nm broadband light (BBL). MethodsTwenty-four patients with moderate-to-severe acne vulgaris were included in the study and all patients expressed a strong desire for beauty. After aminolevulinic acid (ALA) gel applied, the entire face was sequentially irradiated by using BBL with a 560 nm cut-off filter (560–1200 nm), followed by BBL with a 420 nm cut-off filter (420–1200 nm). The clinical efficacy was evaluated by the proportion of patients achieving cured response and excellent response (effective rate), based on the percentage of lesions reduction (treatment rate). The fluorescent images and photographs of acne vulgaris were recorded. Pain and other common local adverse reactions during the treatment were also recorded and evaluated. ResultsIn patients with moderate acne, the mean treatment rates were 57.74 ± 16.40 (%) and 87.40 ± 8.521 (%) at the 6th week and 12th week of treatment, respectively. In patients with severe acne, the mean treatment rates were 60.95 ± 12.06 (%) and 85.04 ± 9.115 (%) at the 6th week and 12th week of treatment, respectively. At the 6th and 12th weeks of treatment, the effective rates of patients were 20.00 % and 93.33 % in patients with moderate acne, and 0.000 % and 88.89 % in patients with severe acne, respectively. Pain scores were significantly higher in patients with severe acne compared to patients with moderate acne when receiving 560–1200 nm BBL-PDT. Additionally, patients when receiving 420–1200 nm BBL-PDT exhibited significantly higher pain scores than those when receiving 560–1200 nm BBL-PDT. The degree of erythema was more severe in patients with severe acne than in those with moderate acne. The pigmentation was observed in one patient with moderate acne and one patient with severe acne. ConclusionThe 560–1200 nm and 420–1200 nm BBL-PDT therapy can effectively treat moderate-to-severe acne vulgaris with tolerable adverse reactions, providing a new option for patients with higher esthetic requirements.

Safety and efficacy of the intranasal spray SARS-CoV-2 vaccine dNS1-RBD: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial

The live-attenuated influenza virus vector-based intranasal SARS-CoV-2 vaccine (dNS1-RBD, Pneucolin; Beijing Wantai Biological Pharmacy Enterprise, Beijing, China) confers long-lasting and broad protection in animal models and is, to our knowledge, the first COVID-19 mucosal vaccine to enter into human trials, but its efficacy is still unknown. We aimed to assess the safety and efficacy (but not the immunogenicity) of dNS1-RBD against COVID-19. We did a multicentre, randomised, double-blind, placebo-controlled, adaptive design, phase 3 trial at 33 centres (private or public hospitals, clinical research centres, or Centre for Disease Control and Prevention) in four countries (Colombia, Philippines, South Africa, and Viet Nam). Men and non-pregnant women (aged ≥18 years) were eligible if they had never been infected with SARS-CoV-2, and if they did not have a SARS-CoV-2 vaccination history at screening or if they had received at least one dose of other SARS-CoV-2 vaccines 6 months or longer before enrolment. Eligible adults were randomly assigned (1:1) to receive two intranasal doses of dNS1-RBD or placebo administered 14 days apart (0·2 mL per dose; 0·1 mL per nasal cavity), with block randomisation via an interactive web-response system, stratified by centre, age group (18-59 years or ≥60 years), and SARS-CoV-2 vaccination history. All participants, investigators, and laboratory staff were masked to treatment allocation. The primary outcomes were safety of dNS1-RBD in the safety population (ie, those who had received at least one dose of dNS1-RBD or placebo) and efficacy against symptomatic SARS-CoV-2 infection confirmed by RT-PCR occurring 15 days or longer after the second dose in the per-protocol population (ie, those who received two doses, were followed up for 15 days or longer after the second dose, and had no major protocol deviations). The success criterion was predefined as vaccine efficacy of more than 30%. This trial is registered with the Chinese Clinical Trial Registry (ChiCTR2100051391) and is completed. Between Dec 16, 2021, and May 31, 2022, 41 620 participants were screened for eligibility and 31 038 participants were enrolled and randomly assigned (15 517 in the vaccine group and 15 521 in the placebo group). 30 990 participants who received at least one dose (15 496 vaccine and 15 494 placebo) were included in the safety analysis. The results showed a favourable safety profile, with the most common local adverse reaction being rhinorrhoea (578 [3·7%] of 15 500 vaccine recipients and 546 [3·5%] of 15 490 placebo recipients) and the most common systemic reaction being headache (829 [5·3%] vaccine recipients and 797 [5·1%] placebo recipients). We found no differences in the incidences of adverse reactions between participants in the vaccine and placebo groups. No vaccination-related serious adverse events or deaths were observed. Among 30 290 participants who received two doses, 25 742 were included in the per-protocol efficacy analysis (12 840 vaccine and 12 902 placebo). The incidence of confirmed symptomatic SARS-CoV-2 infection caused by omicron variants regardless of immunisation history was 1·6% in the vaccine group and 2·3% in the placebo group, resulting in an overall vaccine efficacy of 28·2% (95% CI 3·4-46·6), with a median follow-up duration of 161 days. Although this trial did not meet the predefined efficacy criteria for success, dNS1-RBD was well tolerated and protective against omicron variants, both as a primary immunisation and as a heterologous booster. Beijing Wantai Biological Pharmacy Enterprise, National Science and Technology Major Project, National Natural Science Foundation of China, Fujian Provincial Science and Technology Plan Project, Natural Science Foundation of Fujian Province, Xiamen Science and Technology Plan Special Project, Bill & Melinda Gates Foundation, the Ministry of Education of China, Xiamen University, and Fieldwork Funds of Xiamen University.

Phase I study of a non-S2P SARS-CoV-2 mRNA vaccine LVRNA009 in Chinese adults

BackgroundCOVID-19 caused by SARS-CoV-2 is a great threat to public health. We present the safety and immunogenicity data from a phase I trial in China of an mRNA vaccine (LVRNA009). MethodsIn the single-centre, double-blind, placebo-controlled and dose-escalation study, 72 healthy unvaccinated adults aged 18–59 years were randomized (3:1) to receive LVRNA009 with one of three vaccine dosage (25, 50 and 100 μg) or placebo, to evaluate for the safety, tolerability and immunogenicity of LVRNA009. ResultsAll these participants received two injections 28 days apart. No adverse events higher than grade 2 were reported during the study. A total of 30 participants (42 %) reported solicited adverse reactions during the first 14 days after vaccinations. Of the events reported, fever (n = 11, 15 %) was the most common systemic adverse reaction, and pain at the injection site (n = 17, 24 %) was the most frequent solicited local adverse reaction. Anti-S-protein IgG and neutralising antibodies were observed to have been induced 14 days after the first dose, significantly increased 7 days after the second dose, and remained at a high level 28 days after the second dose. Specific T-cell responses peaked 7 days and persisted 28 days after second vaccination. ConclusionLVRNA009 has demonstrated promising results in safety and tolerability at all three dose levels among Chinese adults. LVRNA009 at three dose levels could rapidly induce strong humoral and cellular immune responses, including binding and neutralising antibody production and IFN- γ secretion, which showed good immunogenicity.Clinical trial registration number:Clinicaltrials.gov NCT05364047; Chictr.org.cn ChiCTR2100049349.