The Detection of Neutralizing Antibody to Lymphocytic Choriomeningitis Virus in Mice

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Abstract
Summary: Neutralization tests were done on a variety of human and animal anti-LCM sera utilizing the mouse f.p. inoculation route, which proved to be more sensitive than the i.c. or i.p. route in detecting antibody. The animal's immune status paralleled its f.p. response and refinement of doubtful results with poorly neutralized sera could be obtained by challenging survivors i.c. to determine the immunity end point. If rapid information was desired the mouse i.p. route combined with assay by weight change measurement proved only slightly less sensitive than the f.p. route. Salt-free bovine serum albumin as a virus and serum diluent increased the sensitivity of the f.p. neutralization test approximately 600 times. Neutralization was demonstrated following inoculation of virus and antisera in different f.p. of the mouse on the same or on different days, but this method was not as quantitatively sensitive as the inoculation of mixtures. Protection was also noted when the serum was given by the i.p. route and the virus by the f.p. route. Low levels of antibody were detected in LCM immune mouse sera 20 to 60 days after infection using the SFA diluent-f.p. method. No neutralizing antibody was detected in PTI (LCM neonatally inoculated) mice. High titers of neutralizing antibody were found in mice which had suppressed LCM virus infection several months previously. This reverses the previously held view that mice could not normally develop significant neutralizing LCM antibody, and shows that their response in this respect is normal, but extremely slow. These results are discussed in relation to their bearing on the pathogenesis of slow virus disease.

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