Humoral and Cellular Immune Responses to Yersinia pestis Infection in Long-Term Recovered Plague Patients

Abstract

Plague is one of the most dangerous diseases and is caused by Yersinia pestis. Effective vaccine development requires understanding of immune protective mechanisms against the bacterium in humans. In this study, the humoral and memory cellular immune responses in plague patients (n ‫؍‬ 65) recovered from Y. pestis infection during the past 16 years were investigated using a protein microarray and an enzyme-linked immunosorbent spot assay (ELISpot). The seroprevalence to the F1 antigen in all recovered patients is 78.5%. In patients infected more than a decade ago, the antibody-positive rate still remains 69.5%. There is no difference in the antibody presence between gender, age, and infected years, but it seems to be associated with the F1 antibody titers during infection (r ‫؍‬ 0.821; P < 0.05). Except F1 antibody, the antibodies against LcrV and YopD were detected in most of the patients, suggesting they could be the potential diagnostic markers for detecting the infection of F1-negative strains. Regarding cellular immunity, the cell number producing gamma interferon (IFN-␥), stimulated by F1 and LcrV, respectively, in vitro to the peripheral blood mononuclear cells of 7 plague patients and 4 negative controls, showed no significant difference, indicating F1 and LcrV are not dominant T cell antigens against plague for a longer time in humans. Our findings have direct implications for the future design and development of effective vaccines against Y. pestis infection and the development of new target-based diagnostics.

LcrV Delivered via Type III Secretion System of Live Attenuated Yersinia pseudotuberculosis Enhances Immunogenicity against Pneumonic Plague

“…Mice vaccinated with Y. pestis KIM5 (lacking pgm) generated the CD4 and CD8 T cells that synergistically conferred protection against plague, but T cells from those vaccinated mice could not recognize LcrV (47). Patients who had recovered from plague also barely produced memory T-cell responses to LcrV antigens (58). Pettersson et al analyzed the localization of LcrV during infection of HeLa cells and were unable to detect any LcrV in the cytosol of the cells (59), but Nilles et al showed that small amounts of LcrV entered HeLa cells and suggested that this translocation appears to not result from injection via the T3SS (60).…”

Rational Considerations about Development of Live Attenuated Yersinia pestis Vaccines

“…Nevertheless, a single dose of the EV NIIEG live vaccine conferred a prompt (day 7 post-vaccination) and pronounced immunity in vaccinees lasting for 10–12 months against bubonic and, to some extent, pneumonic plague [14, 85]. Yang’s group also posed hypothesis that the lack of the pgm locus might affect survival ability of EV76 in humans efficiently, limit its replication and dissemination and result in insufficient contact with immune cells [86], which might develop effectively adaptive immunity. Thus, the fully virulent Y. pestis strain as an origin to develop live efficacious vaccines might be an optimal choice.…”

“…The study indicated that the seroprevalence to the F1 antigen in all recovered patients is 78.5%. In patients infected more than a decade, the antibody-positive rate still remains 69.5% [86]. The positive occurrence of the F1 antibody in patients was high, but approximately 30% of the recovered patients remained sero-negative to both F1 and LcrV antigens.…”

“…The positive occurrence of the F1 antibody in patients was high, but approximately 30% of the recovered patients remained sero-negative to both F1 and LcrV antigens. Moreover, the amount of antibodies in some patients was very low [86]. …”

A Bivalent Typhoid Live Vector Vaccine Expressing both Chromosome- and Plasmid-Encoded Yersinia pestis Antigens Fully Protects against Murine Lethal Pulmonary Plague Infection

“…Although clinical isolates of Y. pestis lacking F1 expression have been reported (39), expression of LcrV is an absolute requirement for virulence in plague (40,41). In addition, serum antibodies from patients fully recovered from naturally occurring bubonic plague were reported to predominantly recognize both F1 and LcrV antigens for up to 10 years postinfection (42). Therefore, both F1 and LcrV are considered key protective antigens for incorporation into a bivalent plague vaccine.…”