Safety and efficacy of novel dermal and epidermal microneedle delivery systems for rabies vaccination in healthy adults.

In the present pilot study, intradermal ID delivery systems with a BD microneedle from 1 to 3mm in length, and epidermal delivery (BD skin abrader) through abraded skin surface relative to standard intramuscular injection were evaluated. Circulating neutralizing antibodies were measured against the rabies virus after the Vero cells rabies vaccine was administered at D0, D7, D21 and D49. This clinical evaluation in 66 healthy volunteers shows that ID delivery using BD microneedle technology of 1/4 the IM antigen dose is safe, efficient and reliable, resulting in a protective seroconversion rate.

Microneedle-based intradermal delivery enables rapid lymphatic uptake and distribution of protein drugs.

Purpose: The purpose of this research was to examine the pharmacokinetics (PK) of drug uptake for microneedle-based intradermal (ID) delivery of several classes of protein drugs compared to standard subcutaneous (SC) administration.

Methods: Systemic absorption kinetics of various proteins were analyzed following microneedle-based ID delivery and standard injection methods in the swine model. Comparative PK data were determined using standard non-compartmental techniques based on blood serum levels.

Microneedle-based vaccines.

The threat of pandemic influenza and other public health needs motivate the development of better vaccine delivery systems. To address this need, microneedles have been developed as micron-scale needles fabricated using low-cost manufacturing methods that administer vaccine into the skin using a simple device that may be suitable for self-administration. Delivery using solid or hollow microneedles can be accomplished by (1) piercing the skin and then applying a vaccine formulation or patch onto the permeabilized skin, (2) coating or encapsulating vaccine onto or within microneedles for rapid, or delayed, dissolution and release in the skin, and (3) injection into the skin using a modified syringe or pump.

Protective immunity in mice achieved with dry powder formulation and alternative delivery of plague F1-V vaccine.

The potential use of Yersinia pestis as a bioterror agent is a great concern. Development of a stable powder vaccine against Y. pestis and administration of the vaccine by minimally invasive methods could provide an alternative to the traditional liquid formulation and intramuscular injection.

Cutaneous delivery of prophylactic and therapeutic vaccines: historical perspective and future outlook.

The skin has long been recognized as an attractive target for vaccine administration. A number of clinical studies have tested the epidermal and dermal routes of delivery using a variety of vaccines over the years. In many cases, cutaneous administration has been associated with immunological benefits, such as the induction of greater immune responses compared with those elicited by conventional routes of delivery.

An alternative approach to combination vaccines: intradermal administration of isolated components for control of anthrax, botulism, plague and staphylococcal toxic shock.

Background: Combination vaccines reduce the total number of injections required for each component administered separately and generally provide the same level of disease protection. Yet, physical, chemical, and biological interactions between vaccine components are often detrimental to vaccine safety or efficacy.

Methods: As a possible alternative to combination vaccines, we used specially designed microneedles to inject rhesus macaques with four separate recombinant protein vaccines for anthrax, botulism, plague and staphylococcal toxic shock next to each other just below the surface of the skin, thus avoiding potentially incompatible vaccine mixtures.

Evaluation of the clinical performance of a new intradermal vaccine administration technique and associated delivery system.

The advantages of intradermal (ID) vaccine administration have been well documented but difficulties in performing ID vaccination using existing techniques and equipment have limited it's clinical application. In the present study, a new ID injection technique and associated microinjection system is described and evaluated in a swine and Human models. Clinical investigation models included: injection site imaging (X-ray and 3D ultrasound echography), histological examination of injection sites, fluid injection volume accuracy measurement, subject' perceived pain and local skin reactivity were specifically developed.

Intranasal administration of dry powder anthrax vaccine provides protection against lethal aerosol spore challenge.

The use of an aerosolizable form of anthrax as a biological weapon is considered to be among the most serious bioterror threats. Intranasal (IN) delivery of a dry powder anthrax vaccine could provide an effective and non-invasive administration alternative to traditional intramuscular (IM) or subcutaneous (SC) injection. We evaluated a dry powder vaccine based on the recombinant Protective Antigen (rPA) of Bacillus anthracis for vaccination against anthrax via IN immunization in a rabbit model.

Preclinical evaluation of microneedle technology for intradermal delivery of influenza vaccines.

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.

Microneedle-based intradermal delivery of the anthrax recombinant protective antigen vaccine.

The recombinant protective antigen (rPA) of Bacillus anthracis is a promising anthrax vaccine. We compared serum immunoglobulin G levels and toxin-neutralizing antibody titers in rabbits following delivery of various doses of vaccine by microneedle-based intradermal (i.d.

Cutaneous delivery of a live, attenuated chimeric flavivirus vaccine against Japanese encephalitis (ChimeriVax)-JE) in non-human primates.

Flaviviral diseases such as yellow fever, Japanese encephalitis (JE) and dengue hemorrhagic fever cause enormous morbidity and mortality worldwide. There is an urgent need for alternative technologies for mass vaccination against these and other diseases, particularly in the developing world. Here, we administered a live attenuated, chimeric JE vaccine (ChimeriVax)-JE) to nonhuman primates by skin microabrasion and intradermal delivery using microneedles.

Formulation of a dry powder influenza vaccine for nasal delivery.

The purpose of this research was to prepare a dry powder vaccine formulation containing whole inactivated influenza virus (WIIV) and a mucoadhesive compound suitable for nasal delivery. Powders containing WIIV and either lactose or trehalose were produced by lyophilization. A micro-ball mill was used to reduce the lyophilized cake to sizes suitable for nasal delivery.

Formulation of a dry powder influenza vaccine for nasal delivery.

The purpose of this research was to prepare a dry powder vaccine formulation containing whole inactivated influenza virus (VIIV) and a mucoadhesive compound suitable for nasal delivery. Powders containing WIIV and either lactose or trehalose were produced by lyophilization. A micro-ball mill was used to reduce the lyophilized cake to sizes suitable for nasal delivery.

Noninvasive delivery technologies: respiratory delivery of vaccines.

This paper reviews the developments in noninvasive methods of drug delivery, with a focus on the delivery of vaccines via the respiratory tract. Recent results indicate that the respiratory system, and the nasal mucosa in particular, provide a valuable target site for immunisation against respiratory and mucosal pathogens. Vaccine delivery via the nasal and pulmonary routes each present distinct sets of performance requirements.

Anthrax vaccine powder formulations for nasal mucosal delivery.

Anthrax remains a serious threat worldwide as a bioterror agent. A second-generation anthrax vaccine currently under clinical evaluation consists of a recombinant Protective Antigen (rPA) of Bacillus anthracis. We have previously demonstrated that complete protection against inhalational anthrax can be achieved in a rabbit model, by intranasal delivery of a powder rPA formulation.

Protective immunization against inhalational anthrax: a comparison of minimally invasive delivery platforms.

A new anthrax vaccine under clinical investigation is based on recombinant Bacillus anthracis protective antigen (rPA). Here, we investigated microneedle-based cutaneous and nasal mucosal delivery of rPA in mice and rabbits. In mice, intradermal (id) delivery achieved up to 90% seroconversion after a single dose, compared with 20% after intramuscular (im) injection.

A novel dry powder influenza vaccine and intranasal delivery technology: induction of systemic and mucosal immune responses in rats.

Intranasal (i.n.) vaccination represents an attractive non-invasive alternative to needle-based injection and provides superior protection at mucosal surfaces.

Improved genetic immunization via micromechanical disruption of skin-barrier function and targeted epidermal delivery.

Skin is an attractive target for delivery of genetic therapies and vaccines. However, new approaches are needed to access this tissue more effectively. Here, we describe a new delivery technology based on arrays of structurally precise, micron-scale silicon projections, which we term microenhancer arrays (MEAs).