On the morphological evaluation of the neurovirulence safety of attenuated mumps virus strains in monkeys

The Mumps Virus Neurovirulence Safety Test in Rhesus Monkeys:A Comparison of Mumps Virus Strains

“…To date, published MNVT results have shown an inconsistent relationship between the neuroattenuation state of mumps viruses for humans and the resultant neurovirulence activity in monkeys [7][8][9]14]. The variable nature of these MNVT results may, in part, be due to the fundamental lack of test standardization.…”

“…Here, M. mulatta monkeys were inoculated intrathalamically with ∼1 human vaccine dose of several different mumps virus strains representing a wide range of pathogenicity. Each group of monkeys was assigned a neurovirulence score (GHLS), which was based on a blinded, biologically meaningful pathologic evaluation of the ventricular and periventricular areas of the brain, as described elsewhere [9,10].…”

“…Each formalin-fixed brain was sectioned, as previously described, to expose the ventricular system, the target area for mumps virus encephalitis [9,10]. Brain sections were embedded in paraffin and stained with gallocyanin.…”

“…Although the neurologic safety of mumps virus vaccine seed strains is assessed in monkeys, published reports of clinical and pathologic outcomes of such testing have not always correlated with the virus strain's neurovirulent potential in humans [7][8][9]. Multiple factors may contribute to this discrepancy.…”

Infection of Mice, Ferrets, and Rhesus Macaques with a Clinical Mumps Virus Isolate

“…Instillation, or injection of a mumps virus inoculum, into Stenson's duct (16,17), parotid gland (18), salivary gland, or thyroid gland (16) of a rhesus macaque, or intraperitoneally in a rare case, could lead to swelling of parotid glands at 4 to 6 days postinfection (dpi) (19), characterized histologically by an infiltration of mononuclear cells and lymphocytes (19). Intracerebral, intrathalamic, intracisternal, and intraspinal injection of various strains of mumps virus in rhesus macaques have been shown to induce cellular infiltration of the cerebral peduncle and perivascular infiltration of lymphocytes (20)(21)(22)(23)(24). Intrauterine infection of pregnant monkeys with mumps virus has been shown to interrupt gestation or lead to delayed hypersensitivity in infants (25).…”