Needle-free vaccine delivery

doi:10.1016/j.addr.2005.12.003

Advanced Drug Delivery Reviews

Volume 58, Issue 1, 20 April 2006, Pages 68-89

https://doi.org/10.1016/j.addr.2005.12.003 Get rights and content

Abstract

The search for methods of vaccine delivery not requiring a needle and syringe has been accelerated by recent concerns regarding pandemic disease, bioterrorism, and disease eradication campaigns. Needle-free vaccine delivery could aid in these mass vaccinations by increasing ease and speed of delivery, and by offering improved safety and compliance, decreasing costs, and reducing pain associated with vaccinations. In this article, we summarize the rationale for delivery of needle-free vaccines and discuss several methods currently in use and under development, focusing on needle-free injection devices, transcutaneous immunization, and mucosal immunization. Jet injectors are needle-free devices that deliver liquid vaccine through a nozzle orifice and penetrate the skin with a high-speed narrow stream. They generate improved or equivalent immune responses compared with needle and syringe. Powder injection, a form of jet injection using vaccines in powder form, may obviate the need for the “cold chain.” Transcutaneous immunization involves applying vaccine antigen and adjuvant to the skin, using a patch or “microneedles,” and can induce both systemic and mucosal immunity. Mucosal immunization has thus far been focused on oral, nasal, and aerosol vaccines. Promising newer technologies in oral vaccination include using attenuated bacteria as vectors and transgenic plant “edible” vaccines. Improved knowledge regarding the immune system and its responses to vaccination continues to inform vaccine technologies for needle-free vaccine delivery.

Introduction

With few exceptions, vaccinations are delivered by injection to the intramuscular, subcutaneous, or intradermal space. This practice has led patients, parents, and practitioners to refer to vaccine administration as “getting one's shots.” Although vaccination delivered by injection has led to tremendous advances in the control of many infectious diseases, this technique is not without risks or discomfort, leading to the search for alternate means of vaccine delivery. Increasing concern over bioterrorism has also led to new needle-free vaccine delivery research [1]. In this article, we summarize the rationale behind the development of needle-free vaccines and discuss a number of the methods of needle-free vaccine administration currently in use or under development. Needle-free vaccination includes all methods for delivering vaccines that do not require a needle and syringe for administration. Our review focuses on three of these techniques: needle-free injection devices, transcutaneous immunization, and mucosal immunization.

Section snippets

Rationale for the pursuit of needle-free vaccine administration methods

Needle-free vaccine delivery is desirable for many reasons. In fact, most descriptions of an ideal or perfect vaccine include a needle-free method of administration [2]. Needle-free vaccine administration has the potential to lead to the following significant advances in immunization delivery: improved safety for the vaccinator, vaccinee, and community; better compliance with immunization schedules; decreased or eliminated injection site pain; easier and speedier vaccine delivery; and reduced

Background

Jet injectors deliver liquid medication or vaccine through a nozzle orifice via a high pressure, high speed narrow stream that penetrates the skin [17], [21]. Drug or vaccine can be delivered to intradermal, subcutaneous, or intramuscular tissue depending on the mechanical properties of the fluid stream [21]. Jet injectors are hand-held; vaccinators hold the nozzle against the skin of a vaccinee, and then use a “trigger” device to release vaccine. The devices come in many different types of

Background

Transcutaneous immunization involves the application of vaccine antigen and often adjuvant to the skin with subsequent penetration to immune cells that reside in the skin. In the past, the skin was seen as a barrier through which vaccines could not be delivered. More recently, the skin, a highly competent immunologic organ, has been proven to be suitable for vaccine delivery [35]. The skin is composed of three layers: the outer layer, the stratum corneum, composed of dead, cornified

Mucosal immunization

Mucosal immunization is the only needle-free method of vaccine delivery that has been commonly and successfully used to date in vaccination programs. The mucosal surfaces of the body are rich immunologic organs, performing constant surveillance for foreign antigens. All mucosal routes and surfaces, including oral, nasal, lung, rectal, conjunctival, and vaginal mucosa have been considered as potential sites [7]. Due to practical reasons and expected lack of cultural acceptance of certain of

Conclusions

Needle-free vaccine delivery is desirable for many reasons including improved safety, better compliance, decreased pain (which is especially important in children), easier and faster vaccine delivery, and likely reduced costs compared to vaccines delivered by needle and syringe. These advantages are helpful in many circumstances and perhaps are most notable in the setting of mass immunizations necessary due to natural pandemics, immunization campaigns in the developing world, and bioterrorism

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Lewisite is a chemical warfare agent intended for use in World War and a potential threat to the civilian population due to presence in stockpiles or accidental exposure. Lewisite-mediated skin injury is characterized by acute erythema, pain, and blister formation. N-acetyl cysteine (NAC) is an FDA-approved drug for acetaminophen toxicity, identified as a potential antidote against lewisite. In the present study, we have explored the feasibility of rapid NAC delivery through transdermal route for potentially treating chemical warfare toxicity. NAC is a small, hydrophilic molecule with limited passive delivery through the skin. Using skin microporation with dissolving microneedles significantly enhanced the delivery of NAC into and across dermatomed human skin in our studies. Microporation followed by application of solution (poke-and-solution) resulted in the highest in vitro delivery (509.84 ± 155.04 µg/sq·cm) as compared to poke-and-gel approach (474.91 ± 70.09 µg/sq·cm) and drug-loaded microneedles (226.89 ± 33.41 µg/sq·cm). The lag time for NAC delivery through poke-and-solution approach (0.23 ± 0.04 h) was close to gel application (0.25 ± 0.02 h), with the highest for drug-loaded microneedles (1.27 ± 1.16 h). Thus, we successfully demonstrated the feasibility of rapid NAC delivery using various skin microporation approaches for potential treatment against lewisite-mediated skin toxicity.
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^☆: This review is part of the Advanced Drug Delivery Reviews theme issue on “Challenges in Pediatric Drug Delivery: the Case of Vaccines”, Vol. 58/1, 2006.

View full text

Needle-free vaccine delivery☆

Abstract

Introduction

Section snippets

Rationale for the pursuit of needle-free vaccine administration methods

Background

Background

Mucosal immunization

Conclusions

Vaccine

J. Allergy Clin. Immunol.

Immunol. Allergy Clin. North Am.

Lancet Neurol.

Lancet, Infect. Dis.

Vaccine

Vaccine

Vaccine

Vaccine

J. Invest. Dermatol.

Adv. Drug Deliv. Rev.

Vaccine

Vaccine

Vaccine

Vaccine

Lancet

Vaccine

Prim. Care

Vaccine

Lancet, Infect. Dis.

Vaccine

Vaccine

Vaccine

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CMAJ

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New High Speed Jet Injectors for Mass Vaccination: Pros and Cons of DCJIs Versus MUNJIs

Clinical immunogenicity and tolerance studies of liquid vaccines delivered by jet-injector and a new single-use cartridge (Imule): comparison with standard syringe injection. Imule Investigators Group

Vaccine

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

Arch. Intern. Med.

Epidermal powder immunization induces both cytotoxic T-lymphocyte and antibody responses to protein antigens of influenza and hepatitis B viruses

J. Virol.

Clinical immunogenicity of measles, mumps and rubella vaccine delivered by the Injex jet injector: comparison with standard syringe injection

Pediatr. Infect. Dis. J.

Transcutaneous immunization