Procedia in vaccinology最新文献

Veterinary vaccines contribute to improved human and animal health and welfare by preventing diseases and deaths caused by a wide range of infectious agents. However, testing necessary to ensure vaccine effectiveness and safety can involve large numbers of animals and significant pain and distress. NICEATM and ICCVAM convened an international workshop to review the state of the science of human and veterinary vaccine potency and safety testing methods and to identify opportunities to advance new and improved methods that can further reduce, refine, and replace animal use. This workshop report is the fourth in a series of six, and addresses methods and strategies for veterinary vaccine potency testing that can avoid or lessen pain and distress, improve animal welfare, and reduce animal use. Vaccine potency tests considered to have the highest priority for further reduction and refinement were those that require an infectious agent challenge test or an in vivo toxin neutralization test, those that require large numbers of animals, and those that require the use of infectious agents hazardous to laboratory workers and/or animals. Vaccines identified as high priorities for improved alternative test methods were rabies, Clostridium spp., Leptospira spp., foreign animal diseases (e.g., foot and mouth disease), and poultry and fish vaccines. The workshop recommended priority research, development, and validation activities to address critical knowledge and data gaps, including opportunities to apply new science and technology. Recommendations to support more humane animal use included development and use of humane endpoints for all challenge tests, development of serologic assays to replace challenge tests, and development of in vitro toxin neutralization tests to replace in vivo TNTs. Workshop participants recommended approaches to reduce the number of animals required for potency testing, and recommended enhanced international harmonization and cooperation, and closer collaborations between human and veterinary researchers to expedite progress in the development and application of alternative methods. Implementation of the workshop recommendations is expected to advance new methods for veterinary vaccine potency testing that will benefit animal welfare and reduce animal use while ensuring continued protection of human and animal health.

European technical requirements for veterinary vaccines are laid down in Annex 1, Title II, to Directive 2001/82/EC, as amended by Directive 2009/9/EC, and the European Pharmacopoeia (Ph. Eur.). Safety tests carried out on each batch are generally overdosage studies carried out in at least one of the most sensitive target species and by at least the recommended route of administration that poses the greatest risk. The dose administered should preferably be twice the standard dose for inactivated vaccines and ten times the standard dose for live vaccines. Each batch must also be tested to show that it will contain the appropriate potency or titer to ensure its safety and efficacy. Live vaccines are usually tested by in vitro titration, while serological or challenge tests in vaccinated animals are commonly used for inactivated vaccines, although alternative methods are encouraged if satisfactorily validated. Several amendments have been introduced into the Ph. Eur. to facilitate reduction in the severity of tests and the numbers of animals used, including: the ability to waive the batch safety test when consistency of production has been established; in vitro methods to test for extraneous viruses in live poultry vaccines; and humane endpoints for rabies vaccine potency tests. This report discusses some preliminary conclusions concerning how these changes have affected the numbers of animals used during batch control testing of vaccines released via the UK batch release scheme.

Veterinary vaccines must be safe, pure, potent, and effective. Potency tests help ensure that each consistently manufactured batch of vaccine provides a level of protection as determined in the original efficacy study throughout the products shelf life. Currently approved assays range from host animal vaccination and challenge to the quantification of specific protective antigens using in vitro technology. The development, maintenance, and update of in vitro potency assays continue to be a priority for both the animal health industry and the corresponding regulatory agencies. New assay development emphasis is being placed on assays that currently involve laboratory animal vaccination/challenge such as vaccines containing the Leptospira and Clostridium spp. antigens. This paper provides an overview of various in vitro potency assays available, the factors that can impact the accuracy of these methods, and specific considerations to be taken into account during assay development.

Nosocomial infectious diseases (e.g. influenza, pertussis) are a threat particularly for immunocompromised and vulnerable patients. Although vaccination of healthcare workers (HCWs) constitutes the most convenient and effective means to prevent nosocomial transmissions, vaccine uptake among HCWs remains unacceptably low. Worldwide, numerous studies have demonstrated that nurses have lower vaccination rates than physicians and that there is a relationship between receipt of vaccination by HCWs and knowledge. Measures to improve vaccination rates need to be profession-sensitive as well as specific in their approach in order to achieve sustained success.

The Virus-Serum-Toxin Act of 1913 provides the legal basis for the regulation of veterinary biological products in the United States, and the USDA's Center for Veterinary Biologics (CVB) has the authority to issue licenses and permits for such products. The law was intended to establish standards and control the importation of products into the United States as well as the domestic distribution of products, assuring the purity, safety, potency, and efficacy of veterinary biological products. Prelicensing data evaluation procedures are designed to assess the quality of each product and support product label claims. Under the standard licensing process, this spectrum of evaluation includes complete characterization of seed material and ingredients, and laboratory- and host-animal safety and efficacy studies. Post-license testing includes batch tests for purity, safety, and potency. As part of the production and testing of regulated products, procedures involving animals are used to validate product requirements for safety, potency, and efficacy. Incorporating alternative methods to reduce, refine, and replace the use of animals in the development and testing of veterinary biological products has been a strategic goal for the CVB for several decades, and current licensing processes and policies are designed to support and encourage the shift from animal-based methods to alternative practices while ensuring that regulated products continue to be safe and effective.

This paper describes the development of an in vitro assay to replace in vivo potency testing for the batch release of inactivated Newcastle Disease virus vaccines. The assay involves the extraction of inactivated antigen from oil emulsion vaccines, the most common adjuvant for poultry vaccines. An enzyme-linked immunosorbent assay (ELISA) is used to quantify the hemagglutinin-neuraminidase (HN) protein of the virus, which was demonstrated to correlate with protection levels.

Validation experiments showed that the method could be used for HN antigen regardless of virus strain or method of inactivation. From the results of these tests it was concluded that this method could replace the in vivo methods that were prescribed in European Pharmacopoeia (Ph. Eur.) Monograph 0870 on inactivated Newcastle Disease vaccines. Large quantities of the necessary reagents and reference materials were prepared and tested. The materials were subjected to stability studies to demonstrate their suitability for long-term storage in order to guarantee long-term availability to the international community. A study in three laboratories demonstrated a good correlation of the candidate assay with two existing in vivo assays, good transferability of the assay, and excellent reproducibility of the proposed assay. A collaborative study was organized by the European Directorate for the Quality of Medicines & Healthcare (EDQM) to demonstrate the repeatability and the reproducibility of the candidate in vitro assay. The suitability of the reference reagent as a Ph. Eur. Biological Reference Preparation was also determined. Fourteen laboratories participated in this study. As a result of these efforts, the assay was included in the relevant Ph. Eur. monograph (01/2007:0870). This paper will address not only the technical aspect of this process but also factors that are considered critical for the success of this project.

Background: Immunization coverage is a major health indicator. In Israel, routine childhood immunizations are provided at community public well-baby clinics. Immunization monitoring is an important cornerstone of a national health policy; however data obtained through sampling carries the risk of under-representation of certain population strata, particularly high-risk groups. Despite high national average immunization coverage, specific sub-populations are under-immunized, as highlighted by outbreaks of vaccine-preventable diseases.

Methods: Implementation of a national childhood immunization registry.

Results: The mean national immunization coverage at age two years (2007 data) was: DTaP-IPV-Hib4 (all 95%), HBV3 (99%), MMR1 (97%), HAV1 (93%). These reports are based on a 17% population-based sample in some districts and on cumulative reports in others. The new national immunization registry requires data completeness, protection of confidentiality, compulsory reporting by providers, and links to other computerized health records. It would provide individual immunization data from infancy to adulthood and be accessible to both providers and consumers. During 2008 the Ministry of Health in Israel launched a national immunization registry based on immunization reporting from well-baby clinics using a web-based computerized system. As of December 2010, 210 well-baby clinics are connected to the nascent registry, which includes the records of some 100,000 children.

Conclusions: The comprehensive national immunization registry augurs well for the prospect of evidence-based assessment of the health status of children in Israel.

We measured haemagglutination inhibiting (HI) serum antibody titers to vaccine matched A/H1N1 influenza virus strain and to the new pandemic 2009 A/H1N1 (pH1N1) virus in two groups of volunteers prior and after 2003/2004 or 2007/2008 influenza seasonal vaccine administration. The responses were examined considering the overall volunteers studied in the two winters (144 and 79, respectively) and grouping those subjects in birth cohort classes (1903–1919; 1920–1957; 1958–1977). Before vaccination, HI antibody titers were found in all the groups examined and, on comparing the different age-groups, titers were higher in the younger groups as compared with the oldest against the A/H1N1 seasonal strains but titers were higher in the oldest as compared with the younger ones against the pH1N1 strain. Vaccination induced significant increases in HI titers against the matched A/H1N1 vaccine strains in all the groups examined. The responses satisfied the EMEA criteria and were higher in the youngest volunteers as compared with older groups. Increases were also found in the level of cross-reactive HI antibodies to the new pandemic 2009 A/H1N1 virus although in most instances the requirements of the EMEA were not met.

Influenza A virus of swine origin caused the first pandemic of the 21st century. In accordance with WHO recommendations, pandemic influenza vaccines were manufactured using the A/California/07/2009 (H1N1) strain and these vaccines were first evaluated in preclinical studies.

We evaluated the immunogenicity of the A/California/07/2009 (H1N1) vaccine in both naïve and influenza-primed mice. Animals were intramuscularly-immunized on D0 and D21 with 0.3 or 3 μg of hemagglutinin administered with or without AF03 adjuvant. Immunogenicity of the various formulations was compared to that of other seasonal H1N1 and H5N1 strains. Additionally, we investigated the impact of prior or concomitant immunization with seasonal trivalent inactivated influenza vaccine (TIV). The immune response was assessed by hemagglutination inhibition and microneutralization assays.

In naïve mice, a single dose of unadjuvanted A/H1N1/California/07/2009 vaccine elicited HI titers > 40, and a second vaccine dose strongly increased these titers. In the presence of AF03, even a low vaccine dosage elicited high antibody titers (HI titers > 700). The antibody responses induced by both unadjuvanted and adjuvanted-vaccine were similar to those induced by other seasonal H1N1 strains and were superior to those induced by H5N1 vaccine strains. In mice previously primed with TIV, the unadjuvanted pandemic (H1N1) 2009 vaccine induced higher functional antibody titers than in naïve mice. However the AF03-adjuvanted vaccine induced similar antibody titers in both naïve and primed mice. The concomitant administration of TIV together with pandemic (H1N1) 2009 vaccine did not affect antibody responses generated against A/California/07/2009 or A/Brisbane/59/2007 seasonal H1N1 strain.

The pandemic (H1N1) 2009 unadjuvanted influenza vaccine was shown to be immunogenic in mice after a single immunization. Formulation of the vaccine with AF03 adjuvant strongly increased its immunogenicity and enabledimmune response to the pandemic (H1N1) 2009 or to the H1N1 strain contained in the seasonal TIV.

The protozoan parasite Histomonas meleagridis is the aetiological agent of histomonosis, a highly fatal disease in turkeys with less mortality in chickens. Following the ban of licensed drugs to be used for prophylactic and therapeutic treatment the number of outbreaks increased in recent years, without any suitable and legal option to combat the disease. In various cases the whole flock had to be killed in order to reduce suffering of animals highlighting the importance histomonosis has gained also in the light of animal welfare. Considering the difficulties for licensing new drugs to be used in food producing animals, vaccination would be a new option to combat the disease. In the following presentation the efforts are consecutively presented leading to a safe and efficient vaccine, without any side effects on health and performance of birds. This vaccine could be the basis to prevent suffering and loss of animals due to a non-treatable disease.