A reference, inactivated, epidemic typhus vaccine: clinical trials in man

Abstract

Four lots of inactivated epidemic typhus vaccine being evaluated for possible use as a federal reference vaccine were examined for antigenicity and reactogenicity in man. Based upon toxin-neutralizing (TN) antibody titers, each of the vaccines induced greater than 90% seroconversion in volunteers. The complement-fixing (CF) antibody test was less sensitive than the TN antibody test for determining antibody responses. Both the CF and TN antibody titers and seroconversion rates seen with one group of vaccines were higher than obtained in earlier studies with vaccines manufactured by a different method. None of the vaccines caused immediate reactions at the time of inoculation or delayed reactions in the 1-month period following vaccination. One vaccine induced pronounced constitutional symptoms in five of 10 volunteers. These included abdominal pain, severe malaise and fever. These reactions could not be ascribed to the presence of high quantities of pyrogens or egg protein and the present data indicate that they might have been due to the levels of rickettsial antigen. If substantiated, such a finding would place important restrictions on the quantity of rickettsial antigens permissible in vaccines. One lot of vaccine was selected as suitable for use as a typhus reference. It had a guinea-pig potency titer of 1 : 100, a direct CF antigen titer of 1 : 18, induced a geometric mean TN antibody titer of 1 : 32 following a single inoculation and resulted in 98% seroconversion with only minimal discomfort and reactions in volunteers.