Prevention of pneumonic plague in mice, rats, guinea pigs and non-human primates with clinical grade rV10, rV10-2 or F1-V vaccines

Quenee, Lauriane E.; Ciletti, Nancy; Elli, Derek; Hermanas, Timothy M.; Schneewind, Olaf

doi:10.1016/j.vaccine.2011.06.119

Cited by 58 publications

(55 citation statements)

References 55 publications

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“…These F1-V-based vaccines are efficacious against pneumonic plague in rodents and macaques (52-56); however, protection was variable in African green monkeys (9,12,55,57,58). Further, F1 capsular antigen is dispensable for virulence (59,60) and the LcrV amino acid sequence has diverged among Y. pestis strains (1, 61).…”

Section: Discussionmentioning

confidence: 99%

Intramuscular Immunization of Mice with a Live-Attenuated Triple Mutant of Yersinia pestis CO92 Induces Robust Humoral and Cell-Mediated Immunity To Completely Protect Animals against Pneumonic Plague

Tiner

Sha

Ponnusamy

et al. 2015

Clin. Vaccine Immunol.

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Y ersinia pestis is the causative agent of plague (1), and there has been a rise in the number of plague cases globally in recent years possibly due to climate changes and shifting of the rodent carrier range (2). The organism is classified as a tier 1 select agent (3-5), and the progression of septicemic and pneumonic forms of plague is very rapidly fatal after the first appearance of symptoms (4, 6-8). Alarmingly, antibiotic-resistant strains of Y. pestis have been isolated from plague patients and also have been engineered for bioweaponization (4). Therefore, vaccination is the optimal strategy for human protection against this deadly disease; however, there are currently no Food and Drug Administration (FDA)-licensed plague vaccines available in the United States (9-11).Although a heat-killed plague vaccine composed of the Y. pestis 195/P strain was in use in the United States until 1999, the production of this vaccine was discontinued because of its effectiveness only against the bubonic plague and not the pneumonic form and also because it was highly reactogenic in humans (12, 13). Various live-attenuated Y. pestis EV76 vaccine strains, which lack the pigmentation locus (pgm) required for iron acquisition, provide protection against bubonic and pneumonic plague and are being used in some parts of the world where plague is endemic (9). However, these EV76-based vaccines are not genetically uniform and are also highly reactogenic (14); hence, they do not meet the standards for FDA approval. In addition, the ⌬pgm mutants of Y. pestis (e.g., the KIM/D27 strain) may not be safe because of a reported case of fatal infection in an individual with hemochromatosis (15,16).In an effort to search for a new live-attenuated plague vaccine, we recently constructed a ⌬lpp ⌬msbB ⌬ail triple mutant, with deleted genes encoding Braun lipoprotein (Lpp), an acetyltransferase (MsbB), and the attachment invasion locus (Ail) (17). Lpp

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Section: Discussionmentioning

confidence: 99%

Intramuscular Immunization of Mice with a Live-Attenuated Triple Mutant of Yersinia pestis CO92 Induces Robust Humoral and Cell-Mediated Immunity To Completely Protect Animals against Pneumonic Plague

Tiner

Sha

Ponnusamy

et al. 2015

Clin. Vaccine Immunol.

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“…In addition, live bacteria, such as Salmonella species, Escherichia coli, or Lactococcus lactis, or live viruses, such as replication-deficient adenovirus, vesicular stomatitis virus, vaccinia virus, or raccoon poxvirus, have been used as vectors for the effective delivery of F1 and/or V antigen to induce protective immunity to plague (10,11). Recently, the main focus of plague vaccine research has been to develop subunit vaccines, in particular, those targeting LcrV and F1 antigens, which were found to efficiently protect rodent and cynomolgus macaque against bubonic and pneumonic plague and are well tolerated in humans (12)(13)(14)(15)(16)(17)(18)(19)(20). However, the subunit vaccine had insufficient and highly variable protection against plague in African green monkeys (20,21).…”

mentioning

confidence: 99%

“…Recently, the main focus of plague vaccine research has been to develop subunit vaccines, in particular, those targeting LcrV and F1 antigens, which were found to efficiently protect rodent and cynomolgus macaque against bubonic and pneumonic plague and are well tolerated in humans (12)(13)(14)(15)(16)(17)(18)(19)(20). However, the subunit vaccine had insufficient and highly variable protection against plague in African green monkeys (20,21). Additionally, the usefulness of F1 as a protective antigen is not clear, since F1…”

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confidence: 99%

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

et al. 2014

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“…F1, encoded by the caf1 gene, has a polymeric structure and confers bacterial resistance to phagocytosis (9). The F1-V-based vaccines are generally protective against pneumonic plague in rodents and nonhuman primates (NHPs) and are currently undergoing clinical trials (10)(11)(12)(13)(14)(15)(16)(17). However, considering the natural existence of fully virulent F1-negative Y. pestis strains (18,19) or those that have highly diverged LcrV variants (20,21), such F1-V-based vaccines would most likely not provide optimal protection across all plague-causing Y. pestis strains in humans.…”

mentioning

confidence: 99%

A Replication-Defective Human Type 5 Adenovirus-Based Trivalent Vaccine Confers Complete Protection against Plague in Mice and Nonhuman Primates

Sha

Kirtley

Klages

et al. 2016

Clin Vaccine Immunol

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j Currently, no plague vaccine exists in the United States for human use. The capsular antigen (Caf1 or F1) and two type 3 secretion system (T3SS) components, the low-calcium-response V antigen (LcrV) and the needle protein YscF, represent protective antigens of Yersinia pestis. We used a replication-defective human type 5 adenovirus (Ad5) vector and constructed recombinant monovalent and trivalent vaccines (rAd5-LcrV and rAd5-YFV) that expressed either the codon-optimized lcrV or the fusion gene designated YFV (consisting of ycsF, caf1, and lcrV). Immunization of mice with the trivalent rAd5-YFV vaccine by either the intramuscular (i.m.) or the intranasal (i.n.) route provided protection superior to that with the monovalent rAd5-LcrV vaccine against bubonic and pneumonic plague when animals were challenged with Y. pestis CO92. Preexisting adenoviral immunity did not diminish the protective response, and the protection was always higher when mice were administered one i.n. dose of the trivalent vaccine (priming) followed by a single i.m. booster dose of the purified YFV antigen. Immunization of cynomolgus macaques with the trivalent rAd5-YFV vaccine by the prime-boost strategy provided 100% protection against a stringent aerosol challenge dose of CO92 to animals that had preexisting adenoviral immunity. The vaccinated and challenged macaques had no signs of disease, and the invading pathogen rapidly cleared with no histopathological lesions. This is the first report showing the efficacy of an adenovirus-vectored trivalent vaccine against pneumonic plague in mouse and nonhuman primate (NHP) models. Yersinia pestis is the causative agent of plague and can be transmitted to humans via an infected flea bite or by direct inhalation of the aerosolized bacilli from an infected person or an animal (1, 2). Plague manifests itself in three major forms in humans, namely, bubonic, septicemic, and pneumonic (2). Pneumonic plague is the most feared form due to its rapid onset and associated high mortality rate (1, 2). Y. pestis has been responsible for at least three pandemics in the past, which killed more than 200 million people (3). Current epidemiological records suggest that there are 4,000 human plague cases annually worldwide (2). The emergence of multi-antibiotic-resistant Y. pestis strains from plague patients and the potential of malicious dissemination of recombinantly engineered bacteria as an airborne bioweapon necessitate the development of an effective preexposure and/or postexposure prophylaxis treatment (1, 2).Currently, no Food and Drug Administration (FDA)-licensed plague vaccine exists in the United States, and recent efforts have focused on the development of recombinant subunit plague vaccines consisting of two well-characterized Y. pestis antigens, the F1 capsular antigen and the type 3 secretion system (T3SS) component and effector LcrV (4-8). F1, encoded by the caf1 gene, has a polymeric structure and confers bacterial resistance to phagocytosis (9). The F1-V-based vaccines are generally protective ag...

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Prevention of pneumonic plague in mice, rats, guinea pigs and non-human primates with clinical grade rV10, rV10-2 or F1-V vaccines

Cited by 58 publications

References 55 publications

Intramuscular Immunization of Mice with a Live-Attenuated Triple Mutant of Yersinia pestis CO92 Induces Robust Humoral and Cell-Mediated Immunity To Completely Protect Animals against Pneumonic Plague

Intramuscular Immunization of Mice with a Live-Attenuated Triple Mutant of Yersinia pestis CO92 Induces Robust Humoral and Cell-Mediated Immunity To Completely Protect Animals against Pneumonic Plague

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

A Replication-Defective Human Type 5 Adenovirus-Based Trivalent Vaccine Confers Complete Protection against Plague in Mice and Nonhuman Primates

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