scholarly journals Tolerability, safety and immunogenicity of intradermal delivery of a fractional dose mRNA -1273 SARS-CoV-2 vaccine in healthy adults as a dose sparing strategy

Author(s):  
Geert V.T. Roozen ◽  
Manon Prins ◽  
Rob van Binnendijk ◽  
Gerco den ◽  
Vincent Kuiper ◽  
...  

Background There is an urgent need for fair and equitable access to safe and effective vaccines to end the COVID-19 pandemic. Shortages in reagents and vaccines are a major challenge, as well as limited knowledge on dose response relationship with mRNA COVID-19 vaccines. We explored intradermal fractional dose administration of a mRNA SARS-CoV-2/COVID-19 vaccine as a potential dose-sparing strategy. Methods We conducted a proof-of-concept, dose-escalation, open-label, randomised-controlled vaccine trial (IDSCOVA) in healthy adults aged 18-30 years. To test initial safety, ten participants received 10 μg mRNA-1273 vaccine through intradermal injection at day 1 and 29. Following a favourable safety review, thirty participants were 1:1 randomised to receive 20 μg mRNA-1273 either intradermally or intramuscularly. The primary endpoint was tolerability and safety. The secondary endpoint was seroconversion and specific IgG concentration against SARS-CoV-2 spike S1 and Receptor Binding Domain (RBD) after the second dose at day 43. We compared results to two historical cohorts of non-hospitalised COVID-19 patients and vaccinated individuals. Findings Thirty-eight of forty included participants (median age 25 years) completed the study. There were no serious adverse events. Self-reported local adverse reactions after intradermal delivery were mild, both in the 10 μg and the 20 μg group. In the higher dose group, systemic adverse reactions were more common, but still well tolerated. All 38 participants mounted substantially higher IgG-anti-S1 and IgG-anti-RBD concentrations at day 43 than COVID-19 controls. At day 43, anti-S1 (95% CI) was 1,696 (1,309-2,198) BAU/mL for the 10 μg intradermal group, 1,406 (953.5-2,074) BAU/mL for the 20 μg intramuscular group and 2,057 (1,421-2,975) BAU/mL for the 20 μg intradermal group. Anti-S1 was 107.2 (63-182.2) BAU/mL for the convalescent plasma control group and 1,558 (547.8-4,433) BAU/mL for the individuals vaccinated with 100 μg mRNA-1273. Interpretation Intradermal administration of 10 μg and 20 μg mRNA-1273 vaccine was well tolerated and safe, and resulted in a robust antibody response. Intradermal vaccination has the potential to be deployed for vaccine dose-sparing.

2021 ◽  
Author(s):  
Geert V.T. Roozen ◽  
Margaretha L.M. Prins ◽  
Robert Samuel van Binnendijk ◽  
Gerco den Hartog ◽  
Vincent P. Kuiper ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
pp. 64
Author(s):  
Noa Berar-Yanay ◽  
Sarit Freiman ◽  
Maʹanit Shapira ◽  
Amer Saffoury ◽  
Ameer Elemy ◽  
...  

Background and objectives: The short-term reported antibody response to SARS-COV-2 vaccination in dialysis patients is high, with a seroconversion response rate up to 97%. Data on the long-term durability of this response are scarce. Our objective was to characterize the long-term anti-spike antibody level in dialysis patients. Design, setting, participants, and measurements: In an observational study, we measured SARS-COV-2 anti-spike antibody levels in dialysis patients who completed 2 doses of the BNT162b2 mRNA SAR S-COV-2 vaccine at 1, 3 and 6 months after the second vaccine dose. We compared the response to dialysis patients who were infected with COVD-19 and to a control group of healthcare-employees. Results: One hundred and forty-two dialysis patients who had been vaccinated (ages 64 ± 11.9 years, 61% male), 33 dialysis patients who had COVID-19 infection (ages 54 ± 14.3 years, 55% male) and 104 individuals in the control group (ages 50 ± 12.2 years, 44% male) were included. The response rate in the vaccinated dialysis patients was 94%, 78% and 73% at 1, 3 and 6 months after the second vaccine dose. In the COVID-19 infected dialysis group and in the control group, the response rate remained at 100% over 6 months. The percentage of change in antibody levels between one and 6 months was −66% in the vaccinated dialysis group, −28% in the control group (p < 0.001) and +48% in dialysis patients who had been infected with COVID-19 (p < 0.001). A non-responder status at 6 months was associated with a lower albumin level. No serious adverse events following vaccination were reported. In conclusion: the initially high response rate to the BNT162b2 vaccine in dialysis patients decreases rapidly. Our results indicate that an early booster (3rd) dose, at three months after the second dose, may be advised for this population to preserve the humoral immunity.


Vaccine ◽  
2013 ◽  
Vol 31 (34) ◽  
pp. 3392-3395 ◽  
Author(s):  
Darin Zehrung ◽  
Courtney Jarrahian ◽  
Amy Wales

Author(s):  
Yanchun Che ◽  
Xiaoqiang Liu ◽  
Yi Pu ◽  
Meijian Zhou ◽  
Zhimei Zhao ◽  
...  

Abstract Background We evaluated an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine for immunogenicity and safety in adults aged 18–59 years. Methods In this randomized, double-blinded, controlled trial, healthy adults received a medium dose (MD) or a high dose (HD) of the vaccine at an interval of either 14 days or 28 days. Neutralizing antibody (NAb) and anti-S and anti-N antibodies were detected at different times, and adverse reactions were monitored for 28 days after full immunization. Results A total of 742 adults were enrolled in the immunogenicity and safety analysis. Among subjects in the 0, 14 procedure, the seroconversion rates of NAb in MD and HD groups were 89% and 96% with geometric mean titers (GMTs) of 23 and 30, respectively, at day 14 and 92% and 96% with GMTs of 19 and 21, respectively, at day 28 after immunization. Anti-S antibodies had GMTs of 1883 and 2370 in the MD group and 2295 and 2432 in the HD group. Anti-N antibodies had GMTs of 387 and 434 in the MD group and 342 and 380 in the HD group. Among subjects in the 0, 28 procedure, seroconversion rates for NAb at both doses were both 95% with GMTs of 19 at day 28 after immunization. Anti-S antibodies had GMTs of 937 and 929 for the MD and HD groups, and anti-N antibodies had GMTs of 570 and 494 for the MD and HD groups, respectively. No serious adverse events were observed during the study period. Conclusions Adults vaccinated with inactivated SARS-CoV-2 vaccine had NAb as well as anti-S/N antibody and had a low rate of adverse reactions. Clinical Trials Registration NCT04412538.


Author(s):  
Ali Faisal Saleem ◽  
Ondrej Mach ◽  
Mohammad Tahir Yousafzai ◽  
Zaubina Kazi ◽  
Attaullah Baig ◽  
...  

Abstract Background Fractional dose (one-fifth of full intramuscular dose) of inactivated poliovirus vaccine (fIPV) administered intradermally is used as IPV dose-sparing strategy. We compared the rate of decline of poliovirus antibodies (PVA) in recipients of 2 doses of fIPV or IPV. Methods A community-based randomized controlled trial was conducted in Karachi, Pakistan. Children aged 14 weeks were randomized into fIPV or full IPV (study arms A, B) and received 1 vaccine dose at age 14 weeks and 1 at age 9 months. PVAs were measured at age 14, 18 weeks and 10, 21 months. Results Seroprevalence of poliovirus type 2 antibodies in 170/250 (68%) children after 2 IPV or fIPV doses at age 10 months in A and B reached 100% vs 99% (P = .339), and at 21 months, 86% vs 67% (P = .004). Between age 10 and 21 months antibody log2 titers dropped from ≥ 10.5 to 6.8 in A and from 9.2 to 3.7 in B. Conclusions There was a significant decline in antibody titers 12 months following the second IPV dose. The slope of decline was similar for full IPV and fIPV recipients. The results provide further evidence that fIPV is a viable option for IPV dose-sparing. Clinical Trials Registration NCT03286803.


Author(s):  
Sujatha S. ◽  
Rebecca Samson ◽  
Christopher Amalraj ◽  
Sundaresan Sundaresan

Neglected pain in neonates leads to various ill effects and it can be prevented by using simple and safe non-pharmacological pain relieving measures. Pharmacologic agents are not recommended in neonates for acute pain due toinvasive procedures however, administration of 24% oralsucrose solutionis found to be effective. The objective of this study was to assess the efficacy of 24%oral sucrose in combination with Facilitated tucking during BCG Vaccination through intradermalroute in term neonates which is not done elsewhere. Fifty five healthy term neonates who fulfilled the inclusion criteria such as gestational age above 37 weeks, within 24 hoursof birth age, and neonates delivered only through spontaneous vaginal delivery were included in the study. The study intervention consists of administration of 2 ml of oral 24% sucrose 2 minutes before BCG Vaccination through intradermal route and Facilitated tuckingat the time of vaccination. The primary outcome measure of cumulative NIPS score at 0, 3,5 minuteswas not significant in both the study groups. Whereas there was significant reduction in the level of pain and mean cry time in the neonates of sucrose group. Heart rateand oxygen saturation after intradermal injection also showed significant (p less than 0.001) differenceamong the neonates, who received 24% of oral sucroseand Facilitated tucking than for neonates of control group. Thus oral (24%)sucrose solution given 2 minutes before injection was effective in reducing level of neonatal pain following Intradermal Vaccination. It is a simple, safe and fast acting analgesic and should be considered for minor invasive procedures in term neonates which last for 5-7minutes.


2021 ◽  
pp. 174749302110069
Author(s):  
Heidi Janssen ◽  
Louise Ada ◽  
Sandy Middleton ◽  
Michael Pollack ◽  
Michael Nilsson ◽  
...  

Background: Environmental enrichment involves organisation of the environment and provision of equipment to facilitate engagement in physical, cognitive and social activity. In animals with stroke, it promotes brain plasticity and recovery. Aims: To assess the feasibility and safety of a patient-driven model of environmental enrichment incorporating access to communal and individual environmental enrichment. Methods: A non-randomised cluster trial with blinded measurement involving people with stroke (n=193) in 4 rehabilitation units was carried out. Feasibility was operationalised as activity 10 days after admission to rehabilitation and availability of environmental enrichment. Safety was measured as falls and serious adverse events. Benefit was measured as clinical outcomes at 3 months, by an assessor blinded to group. Results: The experimental group (n=91) spent 7% (95% CI -14 to 0) less time inactive, 9% (95% CI 0 to 19) more time physically, and 6% (95% CI 2 to 10) more time socially active than the control group (n=102). Communal environmental enrichment was available 100% of the time, but individual environmental enrichment was rarely within reach (24%) or sight (39%). There were no between-group differences in serious adverse events or falls at discharge or 3 months nor in clinical outcomes at 3 months. Conclusions: This patient-driven model of environmental enrichment was feasible and safe. However, the very modest increase in activity by people with stroke, and the lack of benefit in clinical outcomes 3 months after stroke do not provide justification for an efficacy trial. Clinical Trial Registration: ANZCTR 12613000796785 Words: 245


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
V Evdokimov ◽  
E Yushchuk ◽  
A Evdokimova ◽  
S Ivanova ◽  
I Sadulaeva

Abstract Purpose To compare clinical efficacy and safety of various treatment regimens with the inclusion of beta-blockers, RAAS antagonists (ACE inhibitors or ARBs), prolonged bronchodilators (LABA, LAMA) in heart failure patients with CAD and COPD. Methods 385 patients (292 men and 93 women), aged 66.3±4.1 years, with CHF classes II to III (NYHA) combined with moderate to severe COPD (GOLD) and with LVEF less than 45% were randomized into nine groups: enalapril + LAMA (control group), nebivolol + enalapril + LAMA, nebivolol + losartan + LAMA, nebivolol + losartan + LABA, nebivolol + losartan + LAMA/LABA, carvedilol + enalapril + LAMA, carvedilol + losartan + LAMA, carvedilol + losartan + LABA, carvedilol + losartan + LAMA/LABA. Patients of all groups received complex CHF treatment comprising diuretics, nitrates, cardiac glycosides (if necessary). Clinical examination, TTE, 6-minute walk test (6MWT), 24-hour electrocardiogram and blood pressure monitoring, respiratory function test were assessed at baseline and after 6 months of treatment. The quality of life was evaluated by MYHFQ, SGRQ and mMRC scale. Results After 6 months of therapy the improvement of clinical condition and quality of life were marked in all groups. At the end of observation period there was a significant improvement of patients clinical condition, quality of life, reduction of mean CHF FC and dyspnea severity, increase of exercise tolerance, slowing of progression of CHF and COPD, improvement of the parameters of intracardiac hemodynamics, structural and functional parameters of the left and right heart (a decrease in the size of the atria, LV volumes and internal dimension at end-diastole and end-systole, cardiac index, LVMMI, an increase of LVEF, a significant decrease in systemic vascular resistance and the pulmonary hypertension grade, significant improvement in systolic and diastolic function of the ventricles, regression of pathological remodeling of the heart, reduction of heart rate, duration and frequency of myocardial ischemia episodes (including its “silent” form). The best results were obtained in groups using a beta-blocker (nebivolol or carvedilol), a RAAS antagonist, and a combination of long-acting bronchodilators (indacaterol and tiotropium) – group 5 and 9. It is worth noting that beta-blockers, LABA and LAMA were well tolerated in all observation groups and serious adverse events were absent. Conclusions The appointment of 3-generation beta-blockers to patients with CHF on the background of CAD and COPD can significantly increase the effectiveness of treatment and does not cause a deterioration in spirometry in patients with such cardiopulmonary pathology. In our opinion, the most important point in the appointment of beta blockers to patients with moderate to severe COPD is low start dose and slow titration of the dose at the beginning of the therapy. It is advisable to include in the complex therapy of such patients a combination of LABA and LAMA as a basic bronchodilator support. Funding Acknowledgement Type of funding source: None


PEDIATRICS ◽  
1984 ◽  
Vol 74 (2) ◽  
pp. 303-305
Author(s):  

The "Red Book," as the Report of the Committee on Infectious Diseases has come to be known, is not a static document, but is subject to frequent revision. Not only does each edition contain new information available to the Committee, but between editions the Committee communicates further changes to the medical profession via Pediatrics. These communications constitute "Updates" to the Red Book. As everyone knows, scientific information proliferates exponentially, and so the Updates have appeared more frequently in recent years. The Update that follows concerns pertussis vaccine, and therefore, it supplements information in the 1982 edition of the Red Book. To place it in context, the entire Red Book section on Pertussis (pp 198 to 202) should be reviewed, as well as the general sections on immunization, particularly the section on Informed Consent (p 4) and the section on Vaccine Dose (p 10). Like many preventable childhood diseases, pertussis is now infrequently reported in this country. Although more than 200,000 cases were reported annually in the 1930s before pertussis vaccine was introduced, only about 2,000 cases are now recognized each year. The success of the vaccine has resulted in the remarkable decline of a formerly feared illness. As the incidence of the disease has declined, adverse reactions attributed to pertussis vaccine have received greater attention and prominence. In the United Kingdom, following Professor G. T. Stewart's alarming reports of brain damage due to pertussis vaccine, immunization rates fell profoundly, and as a result widespread outbreaks of pertussis began to occur.


1985 ◽  
Vol 10 (3) ◽  
pp. 370-374
Author(s):  
A. H. N. ROBERTS ◽  
F. E. V. ROBERTS ◽  
R. I. HALL ◽  
I. H. THOMAS

A series of 418 patients with lacerations of the hands were allocated randomly to a control group or to a group where the injury was treated with povidone iodine before suture. The incidence of infected and imperfectly healed wounds was determined seven days later. As well as the effect of povidone iodine on infection, thirteen other factors were also analysed. The overall infection rate of 5.0% and the 38.5% imperfect healing rate were not significantly affected by povidone iodine treatment, although both were reduced. The figures of four other trials were combined with this trial and this showed a significant effect of povidone iodine treatment. There were no adverse reactions to povidone iodine. It is therefore recommended that hand lacerations should be treated with povidone iodine prior to suture. Other factors found to be significantly important in wound infection or imperfect healing were the condition of the dressing, the part of the hand injured and pain. Patients should be strongly advised to keep their dressing clean and dry.


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