Epidermal immunization by a needle-free powder delivery technology: Immunogenicity of influenza vaccine and protection in mice

Epidermal immunization by a needle-free powder delivery technology: immunogenicity of influenza vaccine and protection in mice.

These recommendations of the Advisory Committee on Immunization Practices (ACIP) update the previous recommendations on human rabies prevention (CDC. Human rabies prevention--United States, 1999: recommendations of the Advisory Committee on Immunization Practices. MMWR 1999;48 [No. RR-1]) and reflect the status of rabies and antirabies biologics in the United States. This statement 1) provides updated information on human and animal rabies epidemiology; 2) summarizes the evidence regarding the effectiveness/efficacy, immunogenicity, and safety of rabies biologics; 3) presents new information on the cost-effectiveness of rabies postexposure prophylaxis; 4) presents recommendations for rabies postexposure and pre-exposure prophylaxis; and 5) presents information regarding treatment considerations for human rabies patients. These recommendations involve no substantial changes to the recommended approach for rabies postexposure or pre-exposure prophylaxis. ACIP recommends that prophylaxis for the prevention of rabies in humans exposed to rabies virus should include prompt and thorough wound cleansing followed by passive rabies immunization with human rabies immune globulin (HRIG) and vaccination with a cell culture rabies vaccine. For persons who have never been vaccinated against rabies, postexposure antirabies vaccination should always include administration of both passive antibody (HRIG) and vaccine (human diploid cell vaccine [HDCV] or purified chick embryo cell vaccine [PCECV]). Persons who have ever previously received complete vaccination regimens (pre-exposure or postexposure) with a cell culture vaccine or persons who have been vaccinated with other types of vaccines and have previously had a documented rabies virus neutralizing antibody titer should receive only 2 doses of vaccine: one on day 0 (as soon as the exposure is recognized and administration of vaccine can be arranged) and the second on day 3. HRIG is administered only once (i.e., at the beginning of antirabies prophylaxis) to previously unvaccinated persons to provide immediate, passive, rabies virus neutralizing antibody coverage until the patient responds to HDCV or PCECV by actively producing antibodies. A regimen of 5 1-mL doses of HDCV or PCECV should be administered intramuscularly to previously unvaccinated persons. The first dose of the 5-dose course should be administered as soon as possible after exposure (day 0). Additional doses should then be administered on days 3, 7, 14, and 28 after the first vaccination. Rabies pre-exposure vaccination should include three 1.0-mL injections of HDCV or PCECV administered intramuscularly (one injection per day on days 0, 7, and 21 or 28). Modifications were made to the language of the guidelines to clarify the recommendations and better specify the situations in which rabies post- and pre-exposure prophylaxis should be administered. No new rabies biologics are presented, and no changes were made to the vaccination schedules. However, rabies vaccine adsorbed (RVA, Bioport Corporation) is no longer available for rabies postexposure or pre-exposure prophylaxis, and intradermal pre-exposure prophylaxis is no longer recommended because it is not available in the United States.

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Human rabies prevention--United States, 2008 : recommendations of the Advisory Committee on Immunization Practices

Intradermal (ID) vaccination can offer improved immunity and simpler logistics of delivery, but its use in medicine is limited by the need for simple, reliable methods of ID delivery. ID injection by the Mantoux technique requires special training and may not reliably target skin, but is nonetheless used currently for BCG and rabies vaccination. Scarification using a bifurcated needle was extensively used for smallpox eradication, but provides variable and inefficient delivery into the skin. Recently, ID vaccination has been simplified by introduction of a simple-to-use hollow microneedle that has been approved for ID injection of influenza vaccine in Europe. Various designs of hollow microneedles have been studied preclinically and in humans. Vaccines can also be injected into skin using needle-free devices, such as jet injection, which is receiving renewed clinical attention for ID vaccination. Projectile delivery using powder and gold particles (i.e., gene gun) have also been used clinically for ID vaccination. Building off the scarification approach, a number of preclinical studies have examined solid microneedle patches for use with vaccine coated onto metal microneedles, encapsulated within dissolving microneedles or added topically to skin after microneedle pretreatment, as well as adapting tattoo guns for ID vaccination. Finally, technologies designed to increase skin permeability in combination with a vaccine patch have been studied through the use of skin abrasion, ultrasound, electroporation, chemical enhancers, and thermal ablation. The prospects for bringing ID vaccination into more widespread clinical practice are encouraging, given the large number of technologies for ID delivery under development.

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Delivery systems for intradermal vaccination

We conducted a randomized controlled trial to evaluate the antibody response of freshman veterinary students to intradermal human diploid-cell rabies vaccine administered concurrently with chloroquine, a drug frequently used for chemoprophylaxis against malaria. Fifty-one students who had not been vaccinated against rabies were enrolled: 26 received 300 mg of chloroquine base per week (the recommended dose for malaria prophylaxis); 25 did not receive chloroquine and served as controls. All subjects received 0.1 ml of rabies vaccine intradermally on days 0, 7, and 28. Chloroquine was administered weekly to the treatment group, beginning nine days before the first dose of vaccine and continuing until day 48. The mean rabies-neutralizing antibody titer for the chloroquine group was significantly lower than that for the control group on each day of testing — i.e., day 28 (P = 0.0094), day 49 (P = 0.0008), and day 105 (P = 0.0002) — although both groups had neutralizing antibody titers on days 49 and ...

Antibody response to preexposure human diploid-cell rabies vaccine given concurrently with chloroquine.

High cost and limited availability of the current hepatitis B virus vaccine lead to underutilization. To address this problem, we performed a vaccine trial comparing the currently recommended regimen of 20 μg of hepatitis B surface antigen (HBsAg) intramuscularly on days 0, 30, and 180, with a more economical regimen of 2 μg of HBsAg intradermally on days 0, 30, and 180. This trial was performed in 50 seronegative health care workers to assess the immunogenicity and local reactogenicity of both vaccine regimens. We found no significant difference in seroconversion between the intradermal group (96%) and the intramuscular group (100%). Mean ratios of test sample value to mean negative control value for antibody to HBsAg at 360 days were not significantly different (intradermal group, 84 ±26; intramuscular group, 120 ±22). Reactions in both groups were minor. Although the optimal dose of HBsAg was not investigated, our data demonstrate that 0.1 mL of inactivated hepatitis B virus vaccine (Heptavax-B) intradermally is immunogenic in healthy adults. Vaccination by this regimen can broaden hepatitis B virus disease prevention. ( JAMA 1985;254:3203-3206)

Clinical evaluation of low-dose intradermally administered hepatitis B virus vaccine. A cost reduction strategy.

To determine antibody responses to small doses of human diploid cell rabies vaccine (HDCV), we determined rabies antibody titers in 124 volunteers who had been vaccinated with one of five primary preexposure regimens. In a sixth group of 47 persons previously vaccinated with duck embryo rabies vaccine (DEV), we evaluated the booster response after a 0.1-mL dose of intradermal (ID) HDCV. Persons in all five groups undergoing primary immunization received three doses of vaccine, one each on days 0, 7, and 28. The dose and route of vaccination for the five groups included 1 mL intramuscular (IM), 0.1 mL ID (two subgroups), 0.1 mL subcutaneous (SC), and 0.25 mL SC. Adequate titers developed in all persons, irrespective of the route or quantity of vaccine. The geometric mean titers (IU/mL) on day 49 in those receiving primary regimens were 12.87 (1.0 mL IM), 7.44 (0.1 mL ID by syringe), 3.05 (0.1 mL by jet injector), 3.17 (0.1 mL SC), and 6.47 (0.25 mL SC). Titers on day 90, while lower, were still acceptable. Adequate antibody titers developed in all persons previously vaccinated with DEV after a single 0.1-mL ID dose of HDCV; however, higher titers developed at day 7 in those who had shown an adequate response to DEV in the past. Results of this study suggest that HDCV may be used ID or SC for primary preexposure rabies prophylaxis and ID for booster immunization. (JAMA1982;247:1138-1142)

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Human Diploid Cell Rabies Vaccine: Effectiveness of Immunization With Small Intradermal or Subcutaneous Doses

Intradermal human diploid cell rabies vaccine (ID HDCV) was licensed for preexposure use in the United States on May 30,1986. We studied the safety and efficacy of this newly approved route and dose of administration. Serologic results were available from 112 (90%) of the 124 persons who participated in an HDCV low-dose preexposure study in which five different ID, intramuscular (IM), and subcutaneous primary immunization regimens were administered. Three 1.0-mL IM doses of vaccine resulted in titers similar to those from three 0.1-mL ID doses when compared 49 days, one year, and two years after primary immunization. Uniformly high postbooster titers occurred in all five groups when ID boosters were administered at one year or two years. Adverse reactions were similar following both ID and IM vaccination. Although ID HDCV can be a cost-effective substitute for IM vaccine, excessive use of unnecessary preexposure booster doses by any route may be inadvisable because of systemic allergic reactions. In addition, poor immune responses to HDCV have been documented in persons vaccinated in some developing countries. This may limit the use of low-dose regimens in some places. ( JAMA 1987;257:1059-1063)

Joe Mallonee

Papers

Human Diploid Cell Rabies Vaccine: Effectiveness of Immunization With Small Intradermal or Subcutaneous Doses

Preexposure Immunization With Intradermal Human Diploid Cell Rabies Vaccine: Risks and Benefits of Primary and Booster Vaccination