Intradermal delivery for vaccine dose sparing: Overview of current issues

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

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

2021 ◽  
Author(s):  
Geert V.T. Roozen ◽  
Manon Prins ◽  
Rob van Binnendijk ◽  
Gerco den ◽  
Vincent Kuiper ◽  
...  
Keyword(s):  
Adverse Reactions ◽  
Vaccine Trial ◽  
Vaccine Dose ◽  
Healthy Adults ◽  
Control Group ◽  
Intradermal Vaccination ◽  
Serious Adverse Events ◽  
Intradermal Delivery ◽  
Fractional Dose ◽  
Dose Sparing

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.

scholarly journals Preclinical Evaluation of Microneedle Technology for Intradermal Delivery of Influenza Vaccines

2007 ◽  
Vol 14 (4) ◽  
pp. 375-381 ◽  
Author(s):  
Jason B. Alarcon ◽  
Andrea Waterston Hartley ◽  
Noel G. Harvey ◽  
John A. Mikszta
Keyword(s):  
Influenza Virus ◽  
Dose Range ◽  
Influenza Vaccines ◽  
Dna Encoding ◽  
Influenza Virus Hemagglutinin ◽  
Plasmid Vaccine ◽  
Intradermal Delivery ◽  
H1n1 Strain ◽  
Dose Sparing ◽  
Human Vaccine

ABSTRACT Recent clinical studies have suggested that, for certain strains of influenza virus, intradermal (i.d.) delivery may enable protective immune responses using a lower dose of vaccine than required by intramuscular (i.m.) injection. Here, we describe the first preclinical use of microneedle technology for i.d. administration of three different types of influenza vaccines: (i) a whole inactivated influenza virus, (ii) a trivalent split-virion human vaccine, and (iii) a plasmid DNA encoding the influenza virus hemagglutinin. In a rat model, i.d. delivery of the whole inactivated virus provided up to 100-fold dose sparing compared to i.m. injection. In addition, i.d. delivery of the trivalent human vaccine enabled at least 10-fold dose sparing for the H1N1 strain and elicited levels of response across the dose range similar to those of i.m. injection for the H3N2 and B strains. Furthermore, at least fivefold dose sparing from i.d. delivery was evident in animals treated with multiple doses of DNA plasmid vaccine, although such effects were not apparent after the first immunization. Altogether, the results demonstrate that microneedle-based i.d. delivery elicits antibody responses that are at least as strong as via i.m. injection and that, in many cases, dose sparing can be achieved by this new immunization method.

scholarly journals One-Year Decline of Poliovirus Antibodies Following Fractional-Dose Inactivated Poliovirus Vaccine

2020 ◽  
Author(s):  
Ali Faisal Saleem ◽  
Ondrej Mach ◽  
Mohammad Tahir Yousafzai ◽  
Zaubina Kazi ◽  
Attaullah Baig ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Vaccine Dose ◽  
Community Based ◽  
Intramuscular Dose ◽  
Fractional Dose ◽  
Antibody Titers ◽  
Dose Sparing ◽  
Rate Of Decline ◽  
One Year

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.

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

2021 ◽  
Author(s):  
Geert V.T. Roozen ◽  
Margaretha L.M. Prins ◽  
Robert Samuel van Binnendijk ◽  
Gerco den Hartog ◽  
Vincent P. Kuiper ◽  
...  
Keyword(s):  
Healthy Adults ◽  
Intradermal Delivery ◽  
Fractional Dose ◽  
Dose Sparing

scholarly journals Evaluation of health system readiness and coverage of intermittent preventive treatment of malaria in infants (IPTi) in Kambia district to inform national scale-up in Sierra Leone

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Maria Lahuerta ◽  
Roberta Sutton ◽  
Anthony Mansaray ◽  
Oliver Eleeza ◽  
Brigette Gleason ◽  
...  
Keyword(s):  
Sierra Leone ◽  
Phase 1 ◽  
Scale Up ◽  
Intermittent Preventive Treatment ◽  
Vaccine Dose ◽  
Preventive Treatment ◽  
Household Survey ◽  
Register Data ◽  
Phase 2 ◽  
Pentavalent Vaccine

Abstract Background Intermittent preventive treatment of malaria in infants (IPTi) with sulfadoxine-pyrimethamine (SP) is a proven strategy to protect infants against malaria. Sierra Leone is the first country to implement IPTi nationwide. IPTi implementation was evaluated in Kambia, one of two initial pilot districts, to assess quality and coverage of IPTi services. Methods This mixed-methods evaluation had two phases, conducted 3 (phase 1) and 15–17 months (phase 2) after IPTi implementation. Methods included: assessments of 18 health facilities (HF), including register data abstraction (phases 1 and 2); a knowledge, attitudes and practices survey with 20 health workers (HWs) in phase 1; second-generation sequencing of SP resistance markers (pre-IPTi and phase 2); and a cluster-sample household survey among caregivers of children aged 3–15 months (phase 2). IPTi and vaccination coverage from the household survey were calculated from child health cards and maternal recall and weighted for the complex sampling design. Interrupted time series analysis using a Poisson regression model was used to assess changes in malaria cases at HF before and after IPTi implementation. Results Most HWs (19/20) interviewed had been trained on IPTi; 16/19 reported feeling well prepared to administer it. Nearly all HFs (17/18 in phase 1; 18/18 in phase 2) had SP for IPTi in stock. The proportion of parasite alleles with dhps K540E mutations increased but remained below the 50% WHO-recommended threshold for IPTi (4.1% pre-IPTi [95%CI 2–7%]; 11% post-IPTi [95%CI 8–15%], p < 0.01). From the household survey, 299/459 (67.4%) children ≥ 10 weeks old received the first dose of IPTi (versus 80.4% for second pentavalent vaccine, given simultaneously); 274/444 (62.5%) children ≥ 14 weeks old received the second IPTi dose (versus 65.4% for third pentavalent vaccine); and 83/217 (36.4%) children ≥ 9 months old received the third IPTi dose (versus 52.2% for first measles vaccine dose). HF register data indicated no change in confirmed malaria cases among infants after IPTi implementation. Conclusions Kambia district was able to scale up IPTi swiftly and provide necessary health systems support. The gaps between IPTi and childhood vaccine coverage need to be further investigated and addressed to optimize the success of the national IPTi programme.

scholarly journals Interim Estimates of COVID-19 Vaccine Effectiveness in a Mass Vaccination Setting: Data from an Italian Province

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 628
Author(s):  
Maria Elena Flacco ◽  
Graziella Soldato ◽  
Cecilia Acuti Martellucci ◽  
Roberto Carota ◽  
Rossano Di Luzio ◽  
...  
Keyword(s):  
Adverse Event ◽  
Retrospective Cohort ◽  
Cox Model ◽  
National Health System ◽  
Vaccine Dose ◽  
Vaccine Hesitancy ◽  
Serious Adverse Event ◽  
Italian Province ◽  
Official Data

This retrospective cohort study compared the rates of virologically-confirmed SARS-CoV-2 infections, symptomatic or lethal COVID-19 among the residents of the Italian province of Pescara who received one or two doses of COVID-19 vaccines, versus the unvaccinated. The official data of the National Health System were used, and a total of 69,539 vaccinated adults were compared with 175,687 unvaccinated. Among the subjects who received at least one vaccine dose, 85 infections (0.12%), 18 severe and 3 lethal COVID-19 cases were recorded after an average follow-up of 38 days. Among the unvaccinated, the numbers were 6948 (4.00%), 933 (0.53%) and 241 (0.14%), respectively. The serious adverse event reports—yet unconfirmed—were 24 out of 102,394 administered doses. In a Cox model, adjusting for age, gender, and selected comorbidities, the effectiveness of either BNT162b2, ChAdOx1 nCoV-19 or mRNA-1273 vaccines was higher than 95% in preventing infections (mostly due to B.1.1.7 variant), symptomatic or lethal COVID-19. No differences were observed across genders, and among the 691 subjects who received the second dose of vaccine later than the recommended date. Although preliminary, these findings support current immunization policies and may help reducing vaccine hesitancy.

scholarly journals A Novel E2 Glycoprotein Subunit Marker Vaccine Produced in Plant Is Able to Prevent Classical Swine Fever Virus Vertical Transmission after Double Vaccination

Vaccines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 418
Author(s):  
Youngmin Park ◽  
Yeonsu Oh ◽  
Miaomiao Wang ◽  
Llilianne Ganges ◽  
José Alejandro Bohórquez ◽  
...  
Keyword(s):  
Vertical Transmission ◽  
Classical Swine Fever Virus ◽  
Neutralizing Antibodies ◽  
Subunit Vaccine ◽  
Vaccine Dose ◽  
Classical Swine Fever ◽  
Fever Virus ◽  
Tissue Samples ◽  
Marker Vaccine ◽  
E2 Glycoprotein

The efficacy of a novel subunit vaccine candidate, based in the CSFV E2 glycoprotein produced in plants to prevent classical swine fever virus (CSFV) vertical transmission, was evaluated. A Nicotiana benthamiana tissue culture system was used to obtain a stable production of the E2-glycoprotein fused to the porcine Fc region of IgG. Ten pregnant sows were divided into three groups: Groups 1 and 2 (four sows each) were vaccinated with either 100 μg/dose or 300 μg/dose of the subunit vaccine at 64 days of pregnancy. Group 3 (two sows) was injected with PBS. Groups 1 and 2 were boosted with the same vaccine dose. At 10 days post second vaccination, the sows in Groups 2 and 3 were challenged with a highly virulent CSFV strain. The vaccinated sows remained clinically healthy and seroconverted rapidly, showing efficient neutralizing antibodies. The fetuses from vaccinated sows did not show gross lesions, and all analyzed tissue samples tested negative for CSFV replication. However, fetuses of non-vaccinated sows had high CSFV replication in tested tissue samples. The results suggested that in vaccinated sows, the plant produced E2 marker vaccine induced the protective immunogenicity at challenge, leading to protection from vertical transmission to fetuses.

scholarly journals Do Corticosteroid Injections for the Treatment of Pain Influence the Efficacy of mRNA COVID-19 Vaccines?

Pain Medicine ◽  
2021 ◽  
Vol 22 (4) ◽  
pp. 994-1000
Author(s):  
Haewon Lee ◽  
Jennifer A Punt ◽  
David C Miller ◽  
Ameet Nagpal ◽  
Clark C Smith ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Ribonucleic Acid ◽  
Direct Evidence ◽  
Corticosteroid Injection ◽  
Vaccine Dose ◽  
Hypothalamic Pituitary Adrenal ◽  
Messenger Ribonucleic Acid ◽  
Corticosteroid Injections

Abstract Myth Corticosteroid injection for the treatment of pain and inflammation is known to decrease the efficacy of the messenger ribonucleic acid (mRNA) vaccines for coronavirus disease 2019 (COVID-19). Fact There is currently no direct evidence to suggest that a corticosteroid injection before or after the administration of an mRNA COVID-19 vaccine decreases the efficacy of the vaccine. However, based on the known timeline of hypothalamic-pituitary-adrenal (HPA) axis suppression following epidural and intraarticular corticosteroid injections, and the timeline of the reported peak efficacy of the Pfizer-BioNTech and Moderna vaccines, physicians should consider timing an elective corticosteroid injection such that it is administered no less than 2 weeks prior to a COVID-19 mRNA vaccine dose and no less than 1 week following a COVID-19 mRNA vaccine dose, whenever possible.

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