Cell-Mediated Protection against PulmonaryYersinia pestisInfection

Abstract

Pulmonary infection with the bacterium Yersinia pestis causes pneumonic plague, an often-fatal disease for which no vaccine is presently available. Antibody-mediated humoral immunity can protect mice against pulmonary Y. pestis infection, an experimental model of pneumonic plague. Little is known about the protective efficacy of cellular immunity. We investigated the cellular immune response to Y. pestis in B-cell-deficient MT mice, which lack the capacity to generate antibody responses. To effectively prime pulmonary cellular immunity, we intranasally vaccinated MT mice with live replicating Y. pestis. Vaccination dramatically increased survival of MT mice challenged intranasally with a lethal Y. pestis dose and significantly reduced bacterial growth in pulmonary, splenic, and hepatic tissues. Vaccination also increased numbers of pulmonary T cells, and administration of T-cell-depleting monoclonal antibodies at the time of challenge abrogated vaccineinduced survival. Moreover, the transfer of Y. pestis-primed T cells to naive MT mice protected against lethal intranasal challenge. These findings establish that vaccine-primed cellular immunity can protect against pulmonary Y. pestis infection and suggest that vaccines promoting both humoral and cellular immunity will most effectively combat pneumonic plague.

Yersinia pestisbiovarMicrotusstrain 201, an avirulent strain to humans, provides protection against bubonic plague in rhesus macaques

“…Several previous studies have demonstrated that IFN-γ and TNF-α contribute to protection against a lethal systemic Y. pestis challenge, and that cytokine-mediated Th1-type cellular immunity is very important to overcome the immunosuppression induced by Y. pestis infection. 7,31,48,49 In this study, we observed that the Y. pestis 201 or the EV induced not only the increase of IFN-γ and TNF-α production but also that of IL-2 secretion, revealing that the Y. pestis 201 or the EV could induce cytokine-mediated Th1-type cellular immune response in Chinese-origin rhesus macaque model. Moreover, the secretion of IL-4, IL-5, or IL-6 was significantly elevated in the immunized groups after immunization with the Y. pestis 201 or the EV.…”

“…20 In addition, subunit vaccines based on F1 and LcrV antigens failed to fully protect African green monkeys, and the adequate evidence about whether or not they will protect humans has yet to be demonstrated. 21,22 Our previous study 23 and several reports 7,24,25 have indicated that subunit vaccines in alhydrogel elicit robust humoral immunity, and their potential to prime effective cellular immunity has yet to be demonstrated. Several studies suggest that antibodies alone may not provide optimal protection against plague, and that vaccines harnessing both humoral and cellular defense mechanisms should provide superior defense.…”

“…Y. pestis killed whole cell vaccines only have a short protection against bubonic plague and are needed for frequent boosting to maintain immunity. 5,6 Live attenuated vaccine EV provides the theoretical advantage of simultaneously priming immunity against many antigens, and is able to elicit both humoral response and cell-mediated immunity, 7,8 and is effective against bubonic and pneumonic plague in humans, but it shows side effects of varying severity and has not been used in the Western world. 5,9,10 Other types of live attenuated plague vaccines to induce protective immunity include the introduction of Y. pestis antigens in live attenuated Salmonella and Y. pseudotuberculosis etc.…”

Role of immune response in Yersinia pestis infection

“…Studies from the Trudeau Institute showed that IFN-, TNF-, and nitric oxide synthase 2, key elements of cellular immunity, provided critical protective functions during humoral defense against lethal pulmonary Y. pestis infection. Vaccination with live Y. pestis (KIM5 pCD1 + , pMT + , pPCP + , pgm -) primes CD4 and CD8 T cells that in synergy protect against mortal pulmonary Y. pestis infection [71].…”

Antigenic Profiling of Yersinia Pestis Infection in the Wyoming Coyote (Canis Latrans)

“…This does not exclude the possibility that stimulation of cell-mediated immunity also may contribute to long-term resistance to plague. A recent study by Parent et al (2005) demonstrated protection against pneumonic disease in B cell-deficient mice (mMT mice) via adoptive transfer of Y. pestis-primed T cells. Focus on this aspect of the host response to plague is a new emergence and remains to be further studied.…”