Serologic Markers for Long-Term Immunity in Humans Vaccinated with Live Yersinia pestis EV NIIEG

Abstract

Live plague vaccines have saved thousands of human lives in the 20th century and have continued to be used in Russia and other countries of the former Soviet Union for prophylaxis of plague. A live attenuated Y. pestis EV strain line NIIEG is used for the routine annual vaccination of plague workers, as well as people from the groups at risk. This vaccination can offer immunity against both bubonic and pneumonic plague. However, serologic markers of the human response to vaccination with EV NIIEG are poorly investigated. It is not clear whether other antigens, in addition to the established capsular antigen F1 and lipopolysaccharide, can elicit specific and long-lasting antibody responses in vaccinees. In this study, a humoral immunity to a panel of recombinant Y. pestis-specific antigens, such as F1, Pla, LcrV, YopM and YscF, was examined in volunteers, who received multiple annual immunizations with EV NIIEG during the period of 5 to 30 years. To evaluate a long-term immune response to these antigens, we chose a cohort of donors, who had their last immunization 4-30 years ago. The immunoblotting technique revealed that sera of 14 out of 17 donors contained antibodies to at least one of the tested antigens. As expected, the occurrence of anti-F1 antibodies was detected in a large group of vaccinees (57%). In contrast, the presence of specific antibodies to either LcrV or YscF was less pronounced (26% and 36%, respectively), and only two donors possessed anti-YopM (10%). Surprisingly, we found that sera of the vast majority of volunteers (82%) gave positive reaction with the outer membrane protease Pla, specific to Y. pestis. This analysis will provide insights into the correlates of immunity elicited in humans by live plague vaccine, aid in the search for markers of exposure to plague, and help to develop new diagnostic protocols.