Improvement and development of rapid chromatographic strip-tests for the diagnosis of rinderpest and peste des petits ruminants viruses.

This paper describes the improvement of a rapid diagnostic test for the detection of rinderpest virus (RPV) at pen-side and the development of a similar test for the detection of another Morbillivirus, peste de petits ruminants virus (PPRV). Using the Svanova Biotech format, prototype chromatographic strip test devices were developed for RPV and PPRV detection. For the RP device, the incorporation of a monoclonal antibody (Mab), which recognises additional RPV strains of RPV lineage 2, enhanced the range of reactivity of the rapid diagnostic test. The device detected antigen in animals infected experimentally with different RPV strains. It also showed detection levels similar to the RP Clearview™ device reported previously. In addition, RPV was also detected under field conditions in Pakistan. A PPRV specific Mab (C77) was used for the development of the PPR test. This Mab recognised a wide range of PPRV isolates and did not show any cross-reactivity with any other virus tested. In animal experiments the device was able to detect viral antigen in eye swabs taken from the animals. The PPRV test should be invaluable for future PPR control eradication programs.

Challenges with advanced therapy medicinal products and how to meet them.

Advanced therapy medicinal products (ATMPs), which include gene therapy medicinal products, somatic cell therapy medicinal products and tissue-engineered products, are at the cutting edge of innovation and offer a major hope for various diseases for which there are limited or no therapeutic options. They have therefore been subject to considerable interest and debate. Following the European regulation on ATMPs, a consolidated regulatory framework for these innovative medicines has recently been established. Central to this framework is the Committee for Advanced Therapies (CAT) at the European Medicines Agency (EMA), comprising a multidisciplinary scientific expert committee, representing all EU member states and European Free Trade Association countries, as well as patient and medical associations. In this article, the CAT discusses some of the typical issues raised by developers of ATMPs, and highlights the opportunities for such companies and research groups to approach the EMA and the CAT as a regulatory advisor during development.

Do biological medicinal products pose a risk to the environment?: a current view on ecopharmacovigilance.

The occurrence of active pharmaceutical substances in the environment is of growing concern. The vast majority of the compounds in question are of low molecular weight, intended for oral use and designed to tolerate, for example, the digestive enzymes in the upper alimentary tract, the harsh milieus found in the acidic stomach, or the microbe rich intestine. Accordingly, these xenobiotic compounds may, due to their inherent biological activity, constitute a risk to the environment. Biological medicinal products, for example recombinant human insulin or monoclonal antibodies, however, are different. They are primarily made up of oligomers or polymers of amino acids, sugars or nucleotides and are thus readily metabolized. They are therefore generally not considered to pose any risk to the environment. Certain classes of biological medicinal products, however, are associated with specific safety issues. Genetically modified organisms as vectors in vaccines or in gene therapy products have attracted much attention in this regard. Issues include the degree of attenuation of the live recombinant vaccine, replication restrictions of the vaccine vector, alteration of the host and tissue tropism of the vector, the possibility of reversion to virulence, and risk to the ecosystem. In this review we discuss the fate and the potential environmental impact of biological medicinal products following clinical use from an ecopharmacovigilance point of view, and review relevant policy documents and regulatory statements.

Neutralization of primary HIV-1 SF13 can be detected in extended incubation phase assays with sera from monkeys immunized with recombinant HIV-1 SF2 gp120.

Phase III efficacy trials of recombinant human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins were postponed. In Phase I and II trials these candidate vaccines had failed to induce neutralizing antibodies against virus which had been isolated by co-culture with human peripheral blood mononuclear cells (PBMC). The aim of the present study was to determine assay conditions for detecting neutralization of primary HIV-1 isolates with sera from immunized individuals. We show that in two immunogenicity trials in rhesus macaques, recombinant HIV-1 SF2 gp120 induced antibodies which neutralized the primary HIV-1 SF13 isolate. Statistically significant in vitro neutralization required assays in which the incubation phase was extended. Sterile immunity was only seen with the highest level of neutralization, induced by a recombinant prime, peptide boost strategy. We recommend that neutralization assays with extended incubation phases should be used to monitor Phase III efficacy trials.

Immunization with recombinant modified vaccinia virus Ankara can modify mucosal simian immunodeficiency virus infection and delay disease progression in macaques.

In the present study, the immunogenicity and protective efficacy of a recombinant vaccinia virus-based simian immunodeficiency virus (SIV) vaccine, given alone or in combination with a protein boost, were investigated. Cynomolgus macaques were immunized intramuscularly with modified vaccinia virus Ankara (MVA) expressing the SIVsm env and gag-pol genes (MVA-SIVsm) at 0 and 3 months (n=4), at 0, 3 and 8 months (n=4) or at 0 and 3 months followed by purified native SIVsm gp148 and recombinant SIVmac p27 in immunostimulatory complexes at 8 months (n=4). One month after the last immunization, the vaccinees, together with four naive control monkeys and four monkeys immunized with wild-type MVA, were challenged intrarectally with 10 MID50 SIVsm. At the time of challenge, antibody titres to SIV Env and lymphocyte proliferation responses to whole viral antigen were highest in vaccinees receiving MVA-SIVsm in combination with protein immunizations. Following rectal challenge, one of these vaccinees was completely protected. A prolonged survival time was observed in two of four monkeys in each of the groups immunized with MVA-SIVsm, in two monkeys given MVA-SIVsm followed by protein and in three of four monkeys given wild-type MVA, compared with naive controls. In conclusion, one monkey given the combined vaccine was protected completely against SIVsm infection. Furthermore, immunization with MVA-SIVsm, as well as wild-type MVA alone, seemed to delay disease progression after mucosal SIV infection in a proportion of the monkeys.