Plague is a deadly infectious disease caused by Yersinia pestis
and there are 1,000 to 5,000 human plague cases reported each year worldwide (20
). Although the fatality rate of infected persons can decrease dramatically if they are treated by effective antibiotics on time, the existence of antibiotic-resistant virulent Y. pestis
strains indicates that an effective vaccine against both bubonic and pneumonic plagues is urgently needed, and the potential misuse for biological warfare or bioterrorism also strengthens this need (5
Three types of vaccines, namely, killed whole-cell (KWC) vaccines, live attenuated vaccines (EV76), and recombinant subunit vaccines, have been developed against plague. Although KWC and EV76 vaccines provide protection against plague in animal models, both have side effects and need repeated immunizations for developing immunity in humans (19
). They are no longer used in humans in the Western world. EV76 is still the vaccine of choice for humans in China. Subunit vaccines based on the capsular protein F1 and one of the type III secretion system proteins, LcrV, have been the focus of recent efforts (1
). This subunit vaccine has been shown to protect mice against respiratory infection by Y. pestis
and has been reported for entry into a phase II study (9
). However, it failed to adequately protect African green monkeys from pneumonic plague (26
). Moreover, the F1 mutant and the LcrV variant strains can possibly circumvent the effectiveness of this subunit vaccine (36
). This highlights the need to identify novel and effective vaccines that can address all forms of plague.
Understanding of the antimicrobial immune responses of the host will enable the discovery of more effective vaccines. The immune mechanism against Y. pestis
is extremely complex and involves a combination of humoral and cellular factors (14
). Studies have focused on the antibody-based humoral immunity, and the majority of these studies employed animal plague models, which cannot reflect the real immune protective mechanisms of humans.
In contrast to the approximately 6 to 12 months of protection in EV76-immunized people (6
), individuals who survived the plague infection could establish the protective responses. They are considered to have acquired immunity against subsequent reinfection of Y. pestis
. The immune responses to Y. pestis
of recovered patients and the persistence of Y. pestis
-induced immunity after infection will provide the most important data that can facilitate the development of effective vaccine.
Although previous studies confirmed that the F1 antibody could persist for 1 to 4 years in humans (18
), there is no report on longer persistence of the F1 antibody and the existence of the antibodies against proteins other than F1 in patients in the long term. In the present study, the serum samples from 65 plague patients who were in recovery for more than 10 years were collected and screened by protein microarray to investigate antibody profile. Meanwhile, the specific memory T cell responses to F1 and LcrV proteins in the recovered patients were also analyzed.