Permissiveness of blood-derived caprine monocytes to infection by caprine arthritis-encephalitis virus increased during in vitro cultivation and differentiation into macrophages, as evidenced by immunofluorescence and release of extracellular infectious virus. The degree of cell susceptibility to virus infection varied among individual goats, independent of age or breed. Caprine arthritis-encephalitis virus infection of macrophages in vitro resulted in no alteration of five characteristic functional activities.
We report the second case of severe postvaccinial encephalitis with acute disseminated encephalomyelitis since smallpox vaccination was reintroduced in 2002. Both affected patients responded dramatically with early intervention of intravenous immunoglobulin. Our patient, who also received concurrent vaccinia immunoglobulin and corticosteroids, demonstrated full recovery.
Isolates of caprine arthritis-encephalitis virus recovered 12 to 18 months after infection of goats were tested for neutralization by using rabbit antisera directed to the original inoculum virus. Only slight differences in neutralization kinetics between the long-term isolates and the original virus were detected, indicating that heterologous rabbit antisera do not detect antigenic variation of the neutralizing epitopes of caprine arthritis-encephalitis virus.
Nanoparticle vaccines synthesized via layer-by-layer (LbL) fabrication were loaded with designed peptides representing epitopes of the attachment (G) and matrix (M2) proteins of respiratory syncytial virus. The CX3C chemokine mimic epitope of RSV-G has been proposed to contribute to inflammatory responses post-challenge while CD8+ T-cell responses against RSV M2 have been shown to limit the severity of infection and inflammatory pathology. Both monovalent designs (G or M2) and multivalent designs (G+M2) were tested. Mice immunized with RSV-G nanoparticles produced antibody responses that recognized the CX3C epitope only in its folded conformation and not in a linearized state. The same sera also bound native RSV-G protein, inhibited binding of RSV-G protein to the CX3CR1 chemokine receptor, and inhibited migration of human leukocytes toward RSV-G protein. Mice immunized with RSV M2 nanoparticles generated CD8+ T-cell responses and in vitro CTL activity against M2-labeled target cells. The multivalent vaccines containing both G and M2 elicited higher antibody responses to RSV-G and, surprisingly, more potent cellular responses against RSV-M2. These novel nanoparticle vaccines are currently being tested for the induction of neutralizing antibody responses and protection from viral challenge. If successful, the LbL nanoparticle fabrication strategy will provide an innovative approach to formulating safe and effective subunit vaccines for respiratory pathogens including RSV.
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