Rapid Induction of Protective Immunity against Pneumonic Plague by Yersinia pestis Polymeric F1 and LcrV Antigens

Abstract

In a recent study, we demonstrated that vaccination with the polymeric F1 capsule antigen of the plague pathogen Yersinia pestis led to the rapid induction of a protective humoral immune response via the pivotal activation of innate-like B1b cells. Conversely, the monomeric version of F1 failed to promptly protect vaccinated animals in this model of the bubonic plague. In this study, we examined the ability of F1 to confer the rapid onset of protective immunity in the more challenging mouse model of the pneumonic plague. Vaccination with one dose of F1 adsorbed on aluminum hydroxide elicited effective protection against subsequent lethal intranasal exposure to a fully virulent Y. pestis strain within a week. Interestingly, the addition of the LcrV antigen shortened the time required for achieving such rapid protective immunity to 4-5 days after vaccination. As found previously, the polymeric structure of F1 was essential in affording the accelerated protective response observed by covaccination with LcrV. Finally, in a longevity study, a single vaccination with polymeric F1 induced a higher and more uniform humoral response than a similar vaccination with monomeric F1. However, in this setting, the dominant contribution of LcrV to long-lasting immunity against a lethal pulmonary challenge was reiterated.

Mind the Gap—A Perspective on Strategies for Protecting against Bacterial Infections during the Period from Infection to Eradication

“…This line of protection was attributed to the activation of innate-like B cell subsets [ 33 , 34 ]. In a following study, it was shown that effective protection against subsequent lethal intranasal exposure to a fully virulent Y. pestis strain is obtained within a week following immunization with F1 adsorbed on alum hydroxide and that the addition of the LcrV antigen reduced the time to generate protective immunity to four to five days after vaccination [ 35 ]. It is intriguing to believe that therapeutic vaccines could be an add-on post-exposure treatment if administered with antibiotics or other antimicrobial treatments.…”

Bacterial Virus Forcing of Bacterial O-Antigen Shields: Lessons from Coliphages

“…These protective layers are generally described as exostructures, which can be mechanically removed without compromising cell viability or integrity. Most of these layers are of a polysaccharide nature and often referred to as capsular polysaccharides (CPS) or exopolysaccharides (EPS), although some capsule types instead consist of proteins [4] and the biofilm matrix often includes multiple types of polymers, including DNA or even filamentous phage particles (reviewed in [5]) in addition to EPS. The formation of such exostructures is optional and present only in certain species and strains of bacteria.…”

Sex differences in immune protection in mice conferred by heterologous vaccines for pneumonic plague

“…This was followed by LAVs with targeted deletions in virulence factors, and subunit vaccines primarily designed to raise immunity against the dominant antigens F1 (capsule antigen Caf1, coating most strains of Y. pestis) and V (type III injectisome cap protein LcrV, essential for virulence and secretion of virulence factors called Yersinia outer proteins [Yops]) (16)(17)(18). Subunit vaccines consisting of F1 and V complexed with adjuvants have been highly protective in several animal models of pneumonic plague (19)(20)(21)(22)(23)(24)(25)(26)(27)(28). However, possible alteration of bacteria, known heterogeneity of the V protein in other Yersinia species, and existence of virulent F1-negative strains of Y. pestis (22,29,30), mean that broader immunity in addition to these proteins is necessary to combat a wide range of bacterial isolates.…”