Immune defense against pneumonic plague

Yersinia pestis is one of the world's most virulent human pathogens. Inhalation of this Gram-negative bacterium causes pneumonic plague, a rapidly progressing and usually fatal disease. Extensively antibiotic-resistant strains of Y. pestis exist and have significant potential for exploitation as agents of terrorism and biowarfare. Subunit vaccines comprised of the Y. pestis F1 and LcrV proteins are well-tolerated and immunogenic in humans but cannot be tested for efficacy, because pneumonic plague outbreaks are uncommon and intentional infection of humans is unethical. In animal models, F1/LcrV-based vaccines protect mice and cynomolgus macaques but have failed, thus far, to adequately protect African green monkeys. We lack an explanation for this inconsistent efficacy. We also lack reliable correlate assays for protective immunity. These deficiencies are hampering efforts to improve vaccine efficacy. Here, I review the immunology of pneumonic plague, focusing on evidence that humoral and cellular defense mechanisms collaborate to defend against pulmonary Y. pestis infection.