Abstract. The in vivo infection of neonatal dogs by the microsporidian protozoan parasite, Encephalitozoon cuniculi, was studied. Microscopic examination of tissues from infected animals showed granulomatous nephritis, meningoencephalitis, hepatitis, and pneumonitis. A large component of the inflammatory infiltrate consisted of plasma cells and lymphocytes. In addition, hyperplasia of B-lymphocyte-dependent regions of lymph nodes and erythrophagocytosis were consistently seen in infected dogs. Infected dogs developed lymphocytosis, hypergammaglobulinemia, anti-encephalitozoon antibodies, and an antigen-specific blastogenic response to E. cuniculi spores. Lymphocyte blastogenic responses to the lectin phytohemagglutinin A (PHA) were depressed compared to controls. Dogs dying during the 2-month experimental trial were bacteremic. The findings of these experiments suggest that postnatal infection results in a demonstrable although seemingly ineffective immune and inflammatory response without detectable clinical disease.

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Measles still causes considerable morbidity and mortality among infants and young children in developing countries. To develop a new public health tool to reduce this burden, we designed two Sindbis virus replicon vaccines encoding measles virus (MV) hemagglutinin (H) and fusion (F) proteins (pMSIN-H and pMSINHFdU). Our goal is to administer the vaccines to young infants at 6 and 10 weeks of age to prime the immune system to safely and effectively respond to subsequent immunization at age approximately 14 weeks with the licensed attenuated measles vaccine. In preparation for a phase 1 clinical trial, studies of plasmid distribution, integration, and toxicology were performed in rabbits. Biodistribution was assessed after a single DNA immunization delivered intradermally by needle-free injection. Toxicity was assessed using a heterologous prime-boost regimen consisting of a repeat-dose DNA prime followed by a live-attenuated measles vaccine boost. The only vaccine-related adverse effects observed were minimal transient erythema, edema, and inflammation confined to the injection site. Plasmids were detected in the subcutis and muscle at the site of inoculation. A small proportion of animals exhibited plasmids in the regional lymph nodes. There was no evidence of plasmid integration into the host genome. Both Sindbis-based vaccine plasmids were immunogenic in rabbits; pMSIN-H elicited higher virus-neutralizing antibody levels. Both vaccines were shown to be well tolerated and suitable for clinical trials and they are currently being tested in phase 1 studies in young adults.

Beagle dogs inoculated intravenously with 1.75 x IO' viable Encephalitozoon cuniculi spores at 12.5 months of age were monitored for 18 months to assess infection in the adult dog. Parameters monitored included packed cell volume, total and differential leukocyte counts, and humoral and cellular responses to infection. Immunoglobulin M and G antibodies directed against the parasite tegument were present throughout the 18 months. Peripheral blood monocytes treated with lymphokines, either antigen specific (E.