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Respiratory syncytial virus (RSV) is a major cause of severe respiratory disease in infants and the elderly. RSV vaccine development has been hampered by results of clinical trials in the 1960s, when formalininactivated whole-RSV preparations adjuvated with alum (FI-RSV) were found to predispose infants for enhanced disease following subsequent natural RSV infection. We have reproduced this apparently immunopathological phenomenon in infant cynomolgus macaques and identified immunological and pathological correlates. Vaccination with FI-RSV induced specific virus-neutralizing antibody responses accompanied by strong lymphoproliferative responses. The vaccine-induced RSV-specific T cells predominantly produced the Th2 cytokines interleukin-13 (IL-13) and IL-5. Intratracheal challenge with a macaque-adapted wild-type RSV 3 months after the third vaccination elicited a hypersensitivity response associated with lung eosinophilia. The challenge resulted in a rapid boosting of IL-13-producing T cells in the FI-RSV-vaccinated animals but not in the FI-measles virus-vaccinated control animals. Two out of seven FI-RSV-vaccinated animals died 12 days after RSV challenge with pulmonary hyperinflation. Surprisingly, the lungs of these two animals did not show overt inflammatory lesions. However, upon vaccination the animals had shown the strongest lymphoproliferative responses associated with the most pronounced Th2 phenotype within their group. We hypothesize that an IL-13-associated asthma-like mechanism resulted in airway hyperreactivity in these animals. This nonhuman primate model will be an important tool to assess the safety of nonreplicating candidate RSV vaccines. Respiratory syncytial virus (RSV) is a member of the familyParamyxoviridae, genus Pneumovirus (3). While associated with relatively mild upper respiratory tract disease in immunocompetent adults, RSV infection is a major cause of severe lower respiratory tract disease in infants, immunocompromised individuals, and the elderly (7). No vaccine against this important pathogen is currently licensed (5). Three major obstacles hamper the development of a safe and effective RSV vaccine. First, the highest RSV-related morbidity and mortality are seen in infants below 6 months of age. A vaccine would therefore have to be effective in the presence of maternally derived RSVspecific virus-neutralizing (VN) antibodies and in children with a relatively immature immune system. Second, natural RSV infection does not induce sustained protective immunity. Therefore, a vaccine should ideally induce a better immune response than natural infection. Both points argue against a classical live attenuated vaccine and favor a subunit vaccine approach. However, development of nonreplicating RSV vaccines has been seriously hampered by a third complication. During vaccine trials in the 1960s, experimental formalin-inactivated whole-RSV (FI-RSV) vaccines were found to predispose infants to enhanced pulmonary disease upon subsequent RSV infection (17). Studies using murine models of RS...

Specific pathogen free (SPF) domestic cats were inoculated with tissue homogenate obtained from a Chinese leopard (Panthera pardusjaponensis) that had died in a North American zoo from a natural infection with canine distemper virus (CDV). The cats developed a transient cell-associated CDV viraemia along with pronounced lymphopenia but did not show any clinical symptoms. Plasma neutralizing-antibody titres against the homologous CDV (A92-27/4, isolated from the Chinese leopard) were consistently higher than against the CDV vaccine strain 'Bussell'. The Chinese leopard CDV isolate showed in vitro biological properties reminiscent of virulent, wild-type CDV strains. Sequence analysis of the H gene of two large felid CDV isolates from the USA (A92-27/4 and A92-6) revealed up to 10 % amino acid changes including up to four additional potential N-linked glycosylation sites in the extracytoplasmic domain as compared to CDV vaccine strains. Phylogenetic analysis was performed using the entire coding region of the H gene and a 388 bp fragment of the P gene of several morbillivirus species. Evidence was obtained that recent CDV isolates from different species in the United States (including isolates from large felids), Europe and Africa are significantly distinct from CDV vaccine strains. All wild-type CDV isolates analysed clustered according to geographical distribution rather than to host species origin. By sequence analysis a CDV epizootic among large felids in a Californian safari park was linked to a virus which most likely originated from feral non-felid carnivores.

A previously unidentified morbiUivirus was isolated from two harbour porpoises , (Phocoena phocoena)

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