Needle-free Jet Injection Research Articles

Needle-Free Jet Injection of a Mixture of Japanese Encephalitis DNA and Protein Vaccines: A Strategy to Effectively Enhance Immunogenicity of the DNA Vaccine in a Murine Model

Combined immunization with gene-based and protein-based vaccines can increase vaccine effectiveness. We previously demonstrated, using a murine model for Japanese encephalitis (JE), that simultaneous immunization with a DNA vaccine (pcJEME) by the intramuscular route and a protein vaccine consisting of subviral extracellular particles (EPs) by the subcutaneous route provided a synergistic increase in immunogenicities of these vaccines. Here, we investigated a novel immunization protocol consisting of a single inoculation with a mixture of DNA and protein vaccines using a needle-free jet injector. Immunization of ddY mice with 1 microg of pcJEME mixed with 1 microg of EPs or a 1/100 dose of commercial inactivated JE vaccine (JEVAX) induced neutralizing antibody titers of 1:40 to 1:80 (90% plaque reduction) 6 weeks after immunization, whereas immunization with DNA or protein alone only induced low titers (< or =1:10). Co-immunization with pcDNA3, a CpGcontaining vector of the vaccine plasmid, increased immunogenicity of JEVAX to some extent. IgG1/IgG2a isotype profiles supported increased production of EPs in pcJEME-inoculated mice by needle-free injection and an adjuvant effect of the vector on immunogenicity of JEVAX.

Findings of Study of Needle-Free Jet-Injection System with Lidocaine Are Contrary To Published Reports: In Response

Findings of Study of Needle-Free Jet-Injection System with Lidocaine Are Contrary To Published Reports: In Response

Genetic immunization by jet injection of targeted pDNA-coated nanoparticles

Genetic immunization strategies have largely focused on the use of “naked” plasmid DNA or the gene gun. However, there remains a clear need to further improve the efficiency and/or cost of potential DNA vaccines. The theoretical basis of our research is to rationally design genetic immunization methodologies for nanoparticle-based delivery systems of plasmid DNA, perhaps in combination with already commercially available needle-free devices, such as the Biojector 2000. These methodologies may both reduce the dose of pDNA required and enhance the breadth and depth of protective immune responses (i.e., humoral and cellular). The purpose of this article is to provide detailed experimental methods to (1) engineer and characterize pDNA-coated cationic nanoparticles (<100 nm) directly from oil-in-water microemulsion precursors and (2) enhance both the breadth and depth of immune responses after immunization of mice with pDNA-coated nanoparticles by different routes of administration, including intradermal, using a needle-free jet injection device.

Evidence for antigen production in muscles by dengue and Japanese encephalitis DNA vaccines and a relation to their immunogenicity in mice

This study demonstrated viral antigen production in muscle tissues following inoculation with DNA vaccines and examined its relation to antibody induction in mice using the flavivirus system. To achieve detectable levels of antigen production, we used a needle-free jet injector and examined 10% homogenate of quadriceps muscle for viral antigens in a sandwich enzyme-linked immunosorbent assay. We compared DNA vaccines against dengue type 1 (designated pcD1ME), dengue type 2 (pcD2ME) and Japanese encephalitis (pcJEME). The amounts of viral envelope (E) antigen contained in muscle homogenate 1, 2, 3 and 4 days following inoculation with 50μg of pcJEME were 1.1, 1.0, 0.3 and <0.1ng/ml, respectively. Muscles from pcD2ME- and pcD1ME-inoculated mice did not contain detectable levels of E antigen (<0.1ng/ml) during 4 days following inoculation. The E amounts released from Vero cells transfected with DNAs were in the order pcJEME>pcD2ME>pcD1ME. Levels of neutralizing antibody induced by two immunizations with 100μg of each DNA vaccine using needle-free or normal needle/syringe injection systems also were in the order pcJEME>pcD2ME>pcD1ME, 2–11 weeks after the first immunization. However, the difference in antibody levels among three DNA vaccines 14–18 weeks after immunization was smaller than that in the early phase of immunization. These results provide fundamental information useful for developing combination DNA vaccines, such as a dengue tetravalent DNA vaccine, which require adjustment of immunogenicity of each component.

Intradermal immunization with novel plasmid DNA-coated nanoparticles via a needle-free injection device

A high population of dendritic cells in the skin makes intradermal (ID) immunization an attractive route. We sought to further enhance immune responses from a previously reported novel nanoparticle-based DNA vaccine delivery system by administering the system intradermally into mouse skin using Biojector ® 2000, a needle-free jet injection device. Two mouse studies were carried out. Balb/C mice ( n=5–6) were immunized on day 0, 7, and 14 by subcutaneous injection or via the Biojector ® 2000 with pDNA alone (CMV-β-galactosidase, 5 μg), pDNA-coated nanoparticles, or β-galactosidase protein (10 μg) adjuvanted with ‘Alum’ (15 μg). On day 28, mice were sacrificed and specific serum IgG and IgA titer, in vitro cytokine release, and cell proliferation of isolated splenocytes were determined. Similar to previous reports, in both mouse studies, SC immunization with pDNA-coated nanoparticles led to over a log increase in specific serum IgG titer as compared to immunization with pDNA alone. For pDNA alone, jet and SC injection did not result in significant differences in IgG titer. In contrast, for pDNA-coated nanoparticles, jet injection led to as high as a 20-fold enhancement in IgG titer over SC injection. In addition, jet injection of pDNA-coated nanoparticles enhanced the IgG titer by more than 200-fold over jet injection of pDNA alone. Also, jet injection of pDNA-coated nanoparticles resulted in significantly enhanced specific serum IgA titer. For in vitro cytokine release, immunization with pDNA-coated nanoparticles by jet injection enhanced IFN-γ and IL-4 release over pDNA alone by 6- and 5-fold, respectively. SC injection of pDNA-coated nanoparticles also resulted in enhanced IFN-γ and IL-4 release over pDNA alone although with less magnitude. Finally, immunization with pDNA-coated nanoparticles, by both jet injection and SC injection, led to improved splenocyte proliferation over pDNA alone. In conclusion, a combination of a novel cationic nanoparticle-based DNA delivery system with ID jet injection led to enhanced antibody production, Th-1/Th-2 balanced cytokine release, and enhanced splenocyte proliferation.

Lidocaine needle-free jet-injection system value for money?

Lidocaine needle-free jet-injection system value for money?

A Needle-Free Jet-Injection System with Lidocaine for Peripheral Intravenous Cannula Insertion: A Randomized Controlled Trial with Cost-Effectiveness Analysis

A Needle-Free Jet-Injection System with Lidocaine for Peripheral Intravenous Cannula Insertion: A Randomized Controlled Trial with Cost-Effectiveness Analysis

Prevalência e fatores associados a marcadores do vírus da hepatite B em população rural do Brasil central

To carry out a survey of hepatitis B virus seroepidemiology in a municipality in central Brazil, on the border of two large ecosystems, the cerrado (savanna) and the Amazon River basin. The municipality studied, Nova Mutum, is located in the north central portion of the Brazilian state of Mato Grosso. The study sample of 754 individuals included persons from families, selected at random, who were living in the municipality's urban center as well as all the individuals living in a nearby rural village. Ages ranged from 2 to 79 years. All eligible individuals were interviewed. Blood was collected and used to assess hepatitis B virus markers by enzyme-linked immunosorbent assay. Hepatitis B virus infection was found in 232 individuals, or 31% of them; 19 of them (3%) were HBsAg-positive. Of the 754 persons, 149 of them (20%) who reported having been vaccinated against hepatitis B and who presented anti-HBs positivity were classified as vaccine responders. With the multivariate analysis, the variables found to be associated with exposure to hepatitis B virus were having begun sexual relations, having been vaccinated against yellow fever with a needle-free jet injection gun (for the age group < 20 years), and being an immigrant from southern Brazil (> 20 years). Vaccine coverage was low among individuals older than 10 years. The largest share of susceptible individuals (74%) were found in the age group of 11 to 20 years. Our data suggest that hepatitis B virus vaccine coverage in Brazil should be extended to include teenagers in populations that have a low to moderate hepatitis B virus prevalence. It is likely that our results can be extrapolated to other areas of Latin America with a similar epidemiological pattern.

Safety and immunogenicity of varying dosages of trivalent inactivated influenza vaccine administered by needle-free jet injectors

To evaluate the perceived pain, other adverse events, and immunogenicity of influenza virus vaccine administered by needle-free jet injector (JI) compared with that of vaccine administered by needle and syringe (N&S), we randomly assigned 304 healthy young adults to receive one of three dosages (0.5, 0.3, or 0.2 ml) of the 1998–1999 season vaccine administered by either of two JI devices or by N&S. In multivariate analysis, female gender and JI administration were associated with higher levels of pain reported at the time of vaccination as well as with the occurrence of local injection site reactions following vaccination. Immune response did not vary significantly by dosage but administration by one JI device was associated with higher post-vaccination H1N1 antibody titers.

Needle-free jet injector produces greater gene expression by naked plasmid DNA in rabbit hindlimb muscles compared to the needle method Hiromi Nishimura, Marianne Kearney, Marcy Silver, David Opie, Robert C. Glines, Diane L. Demarais, Jeffrey M. Isner. St. Elizabeth's Medical Center, Boston, MA

Needle-free jet injector produces greater gene expression by naked plasmid DNA in rabbit hindlimb muscles compared to the needle method Hiromi Nishimura, Marianne Kearney, Marcy Silver, David Opie, Robert C. Glines, Diane L. Demarais, Jeffrey M. Isner. St. Elizabeth's Medical Center, Boston, MA

Safety testing of needle free, jet injection devices to detect contamination with blood and other tissue fluids.

Needle free jet injection guns have been used extensively in both veterinary and human health to deliver both vaccine and drugs, but in recent years, concerns have mounted for their potential to transmit blood borne disease agents among consecutive vaccinates. A Ped-O-Jet type jet injection device was used to deliver serial subcutaneous injections of 0.5 mL saline (as a surrogate for vaccine) into calves and pigs, with intervening ejectates collected in vials to represent what the next vaccinate would have received. An enzyme linked immunosorbant assay was developed to detect species specific albumin as a marker for blood, using calibration standards from known dilutions of bovine or porcine blood. Assay sensitivity of 20 pL/mL corresponded to the estimated minimal chimpanzee infectious dose of 10 pL for hepatitis B virus. The methodology and available results for evaluating the safety of jet injector devices are reported.

Impaired Bioavailability of Interferon Beta-1a when Administered Intramuscularly by Needle-Free Injection

Intramuscular (IM) or subcutaneous (SC) drug administration of small molecules and protein has been demonstrated by use of needle-free jet injection methods. One device that achieves needle-free parenteral administration, BIOJECTORr`, is commercially available and was evaluated for IM delivery of interferon beta-1a. Recombinant human interferon beta-1a (IFN β-1a) is a glycosylated protein containing 166 amino acids and has a molecular weight of 22.5 kDa. Needle-free jet injection of IFN β-1a with the BIOJECTORr` was assessed in a human Phase I trial. The study was a randomized, open-label crossover in which 12 healthy subjects each received 60 μ of IFN β-1a as an IM injection by standard needle administration and by needle-free jet injection. Blood samples for pharmacokinetic (serum activity, PK) and pharmacodynamic (serum neopterin, PD) determinations were collected through 144 hours post-dose. Mean serum antiviral activity AUC values for needle-free and standard needle injection were 218 and 531 U x h/ml, respectively; corresponding Cmax values were 19.7 and 29.0 U/ml. Median Tmax following both treatments was 12 hours. The relative bioavailability of IFN β-1a, needle-free to standard needle injection, was 41.1% with 90% confidence limits of 24.4% to 69.3%. Mean serum neopterin EAUC values for needle-free and standard needle injection were 114 and 325 ng x h/mL, respectively; corresponding Emax values were 2.3 and 5.6 ng/mL. The ratio of serum neopterin EAUC, needle-free to standard needle, was 34.9% with 90% confidence limits of 23.4% to 52.1%. Injection site reactions were substantially more frequent following needle-free injection; however, systemic side effects were less frequent. Intramuscular needle-free jet injection and needle-based injection of a 22.5-kDa glycoprotein do not produce equivalent systemic PK or PD responses.