Safety, tolerability, and immunogenicity of inactivated trivalent seasonal influenza vaccine administered with a needle-free disposable-syringe jet injector

doi:10.1016/j.vaccine.2011.09.097

Vaccine

Volume 29, Issue 51, 28 November 2011, Pages 9544-9550

https://doi.org/10.1016/j.vaccine.2011.09.097 Get rights and content

Abstract

Background

Jet injectors (JIs) avoid safety drawbacks of needle–syringe (N–S) while generating similar immune responses. A new generation of disposable-syringe jet injectors (DSJIs) overcomes the cross-contamination risk of multi-use-nozzle devices used in 20th-century campaigns. In the first study in humans, the newly-US-licensed LectraJet^® model M3 RA DSJI was compared to N–S.

Methods

Sixty healthy adults received one 0.5 mL intramuscular dose of the 2009–2010 seasonal, trivalent, inactivated influenza vaccine (TIV) in randomized, double-masked fashion by either DSJI (n = 30) or N–S (n = 30). Adverse reactions were monitored for 90 days after injection, and serologic responses assayed by hemagglutination inhibition (HI) at days 28 and 90.

Results

There were no related serious adverse events (SAEs), nor differing rates of unsolicited AEs between DSJI and N–S. Solicited erythema and induration occurred more often after DSJI, but were transient and well-tolerated; a trend was noted for fewer systemic reactions by DSJI. Pre-vaccination HI geometric mean titers (GMT) increased by 28 days for H1N1, H3N2, and B antigens by 13-, 14-, and 8-fold via DSJI, and by 7-, 10-, and 7-fold for N–S, respectively. No trending differences in GMT, seroconversion, or seroprotection were noted; sample sizes precluded non-inferiority assessment.

Conclusions

DSJI delivery of TIV is well-tolerated and immunogenic.

Highlights

► This report is the first in human assessment of a newly licensed jet injector LectraJet^® M3 RA. ► Administration of seasonal influenza vaccine using the jet injector was well tolerated. ► The jet injector induced immune responses that were similar to needle and syringe.

Section snippets

Background

Needle-free vaccine delivery has the potential to lead to significant advances in immunization, including improved safety for the vaccinator and vaccinee, better compliance with immunization schedules, decreased fear of injection and needles, easier and speedier vaccine delivery, and reduced cost [1]. For these reasons, needle-free vaccine delivery has been supported by the World Health Organization [2], the Global Alliance for Vaccines and Immunization [3], and the Centers for Disease Control

Subjects

Healthy male and female volunteers aged 18–49 years were recruited from the Baltimore/Washington, DC area for this randomized, controlled, double-masked clinical trial. Volunteers were required to be in good health as evidenced by medical history and physical examination, if indicated. Ineligible were those who received an influenza vaccine in the 2008–2009 or 2009–2010 influenza seasons, received a live-attenuated vaccine within 30 days prior to enrollment or a killed vaccine within 14 days

Results

Sixty-five volunteers were recruited and sixty enrolled and vaccinated in February and March of 2010. Four recruits were removed from the study prior to vaccination because of the exclusion criteria of current use of antimicrobials (two recruits), a positive pregnancy test (one), and a history of a bleeding disorder (one). Another eligible volunteer changed her mind prior to being vaccinated. All thirty volunteers randomly assigned to the DSJI study arm received the vaccine by that route; all

Discussion

In this first human clinical study using LectraJet^® M3 RA to administer TIV vaccination, injection using the DSJI was found to be well-tolerated and immunogenic. Higher rates of transient local reactogenicity were seen in volunteers vaccinated with the LectraJet device compared to N–S, although a trend toward fewer systemic reactions was also noted.

The traditional administration of vaccines via needles poses safety risks for patients, healthcare providers, and the community [11], [12], [13]. An

Acknowledgments

We thank the volunteers for their participation in the clinical trial, as well as the clinical, regulatory, and immunology staff at the Center for Vaccine Development, including Jane Cowan, Karimah Williams, Cara Arcidiacono, Sarah Yang, Virginia Cowan, and Kim Rincavage. We also thank William Blackwelder and Yukun Wu for randomization and statistical advice. Financial support for this research was provided by D’Antonio Consultants International, Inc., which had no technical authority over the

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In this paper we present new results on jet injection with the overall aim of providing an efficient drug delivery into the intradermal region of the skin. To advance upon previous work in this area, we studied the use of various geometries for the nozzle (ampule) tip, which is applied to the skin. The geometries included a regular (flat-top) nozzle, tapered nozzles (conical and parabolic), and one wide base nozzle in order to vary the local stress in the skin layers directly beneath the injector. In all of these geometries, we also varied both the applied load and the skin support (e.g., solid backing vs. porcine tissue). We found that the use of applied load combined with a wider contact area led to more consistent injections with dispersion characteristics that may be preferable for vaccinations utilizing skin-based electroporation.
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Needle-free technology was developed due to fear of hypodermic needles and accidents caused by the use of hypodermic needles. One of the important devices used for needle-free drug delivery are the needle-free jet injectors (NFJI). NFJI have been in use for more than 50 years but still have not been fully exploited. This technology has been evolved from multiple-use nondisposable devices to single use disposable-devices and overcame the risk factors such as needle contamination and any stick injuries. Jet injectors have very simple structure and mechanism based on high pressure. NFJI have wide classification based on the energy, load, mechanism, and site of application and different types of devices can be used based on the disease condition and severity of the patient. Jet injectors provide excellent bioavailability, minimum or no pain, and can be used for a wide range of drugs. In this chapter, a history of NFJI, classification, fluid dynamics behind their operation, challenges, and areas in which these needle-free technologies are being used, is reported. Needle-free technology has enormous biomedical applications including immunization to insulin delivery where NFJI have been widely used.
Experimental investigation of stone drilling using water jet generated by electromagnetic actuator
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This paper aims to experimentally investigate the performance of a high-speed water jet generated by an electromagnetic actuator to drill the stone's surface. The electromagnetic actuator was designed and built by following the impact driven method (IDM). The experiment confirmed that the maximum jet velocity of 239.57 m/s and maximum impact pressure of 133.27 MPa are obtained at the traveling distance of 30 mm, the liquid volume of 0.1 mL, voltage capacity of 500 V, and the nozzle's orifice diameter of 0.5 mm. The performance characteristics, e.g., jet velocity and impact pressure of the water jet generator, have the potential for applying to many medical and engineering applications. The application of a high-speed water jet for stone drilling is investigated as a preliminary study. The water jet was then applied to drill the sandstones. The effects of numbers of a jet pulse to the jet drilling's depth in sandstones were reported, and the failure mechanisms of sandstone are also discussed. Finally, it is concluded that the high-speed water jet generated by the electromagnetic actuator has the potential to apply to stone drilling application.
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Citation Excerpt :
Multiple studies [12–17] now prove that this technique is feasible for mass immunizations, which as shown by the recent pandemic, are going to be vital for forseeable future. Whilst jet injectors were originally proposed as a candidate to replace needles for standard intramuscular injections [18–22], they also clearly hold promise for fractional dose vaccine delivery [12–17], and there have been numerous studies assessing both the fundamental mechanics [23–47] and clinical success [12–17,48–51] of needle-free jet injection. The basic premise is that a high upstream pressure, created using either a spring or compressed gas mechanism, forces a jet at high-speed, vjet ~O(100 m/s), from a narrow orifice, D0 ~O(100 μm).
We report on an experimental study of high-speed micro-scale liquid jets ejected into low-pressure environments, which has applications for the use of negative pressure modules in jet injector systems. The jets were impulsively started by the action of a stiff spring-piston and ejected through a narrow orifice, D₀ ~ 100 μm, into partial vacuums ranging from atmospheric pressure down to −80 kPa. We find that due to the high exit velocity, v_j ~ 100 m/s, the main jet stream is largely unaffected, but we reveal some fascinating fine features during the start-up phase, largely due to the presence of a small liquid volume pulled through the orifice prior to actuating the jet. In particular, as the pressure decreases, the start-up time increases and the initial spray becomes more pronounced. However, the primary outcome of this feasibility study is that use of negative pressures is viable for jet injector applications, and we hypothesize an optimal range of working pressures and configurations.
Characterization of jets for impulsively-started needle-free jet injectors: Influence of fluid properties
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An experimental study was performed to assess the hydrodynamics of liquid jets used for needle-free injection, where the typical orifice diameter is ~155 μm and velocity is in range of ~ 60–140 m/s. The jet is impulsively started by a spring-piston that forces a plunger through a cartridge filled with the liquid. Liquid exiting the orifice then forms a jet. However, despite a fixed spring force, the jet speed can vary significantly depending on the fluid physical properties - in particular - the effective viscosity. Since in practice a wide range of fluids may be used for injection, we seek herein to study the jet formation and speed for a broad range of fluids, characterized by viscosity or rheological profile. In addition, we also characterize the jet performance with a peak impact force, measured by a dynamic load cell, and ex-vivo injection experiments on porcine tissue. We find that jet speeds and impact forces decrease in a non-linear fashion with increasing viscosity, but that shear-thinning effects are significant and can render high jet speeds (>100 m/s) even for low-shear viscosities $μ_{0} ~ 100$ Pa.s.
Characterization of jet injection efficiency with mouse cadavers
2019, Journal of Controlled Release
Needle-free drug delivery is highly sought after for reduction in sharps waste, prevention of needle-stick injuries, and potential for improved drug dispersion and uptake. Whilst there is a wealth of literature on the array of different delivery methods, jet injection is proposed as the sole candidate for delivery of viscous fluids, which is especially relevant with the advent of DNA-based vaccines. The focus of this study was therefore to assess the role of viscosity and jet configuration (i.e. stand-off relative to the skin) upon injection efficiency for a fixed spring-loaded system (Bioject ID Pen). We performed this assessment in the context of mouse cadavers and found that the dominant factor in determining success rates was the time from euthanasia, which was taken as a proxy for the stiffness of the underlying tissue. For overall injection efficiency, ANOVA tests indicated that stiffness was highly significant (P <  < 0.001), stand-off was moderately significant (P < 0.1), and viscosity was insignificant. In contrast, both viscosity and standoff were found to be significant (P < 0.01) when evaluating the percentage delivered intradermally. Using high-resolution micro-computed tomography (μ-CT), we also determined the depth and overall dispersion pattern immediately after injection.

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Safety, tolerability, and immunogenicity of inactivated trivalent seasonal influenza vaccine administered with a needle-free disposable-syringe jet injector

Abstract

Background

Methods

Results

Conclusions

Highlights

Section snippets

Background

Subjects

Results

Discussion

Acknowledgments

Adv Drug Deliv Rev

Vaccine

Vaccine

Vaccine

Vaccine

Can needle-free administration of vaccines become the norm in global immunization?

Nat Med

Clinical studies with jet injection; a new method of drug administration

Curr Res Anesth Anal

An outbreak of hepatitis B associated with jet injections in a weight reduction clinic

Arch. Intern. Med.