One year immunogenicity and safety of subunit plague vaccine in Chinese healthy adults: An extended open-label study.

BACKGROUND: To evaluate the one-year immunogenicity and safety of a subunit plague vaccine. METHODS: In the initial study, 240 healthy adults aged 18-55 years were administrated with 2 doses of 15 or 30 µg plague vaccines at day 0 and 28, respectively. In this extended follow-up study, we evaluated the immunogenicity and safety of the plague vaccine up to one year. RESULTS: For antibody to envelope antigen faction 1 (F1) antigen, titers were up to new peaks at month 6, then declined slowly to month 12, but remained at higher levels than those at day 56. Geometric mean titers (GMTs) of F1 were significantly higher in 30 µg group than those in 15 µg group at month 6 and 12 (P < 0.0001 and P < 0.001). However, approximate 100% seroconversion rates of F1 antibodies were found in both 15 and 30 µg groups at the both time points. For antibody to recombinant virulence (rV) antigen, titers and seroconversion rates were decreased sharply at month 6 and continue to decrease at month 12. GMTs and seroconversion rates were not significantly different between the 15 and 30 µg groups, respectively. No serious adverse events (SAEs) related to vaccine occurred. CONCLUSION: The new plague vaccine (F1+rV) induced a robust immune response up to 12 months and showed a good safety profile in adults aged 18-55 years.

A phase I safety and immunogenicity dose escalation trial of plague vaccine, Flagellin/F1/V, in healthy adult volunteers (DMID 08-0066).

INTRODUCTION: Intentional aerosolization of Yersinia pestis may result in pneumonic plague which is highly fatal if not treated early. METHODS: We conducted a phase 1 randomized, double blind (within each group), placebo controlled, dose escalation trial to evaluate a plague vaccine, Flagellin/F1/V, in healthy adults aged 8 through 45years. Vaccine was administered intramuscularly on Days 0 and 28 at a dose of 1, 3, 6 or 10mcg. Subjects were observed for 4h after vaccination for cytokine release syndrome. Reactogenicity and adverse events (AE) were collected for 14 and 28days, respectively, after each vaccination. Serious AE were collected for the entire study. ELISA antibody and cytokines were measured at multiple time points. Subject's participation lasted 13months. RESULTS: Sixty healthy subjects were enrolled; 52% males, 100% non-Hispanic, 91.7% white and mean age 30.8years. No severe reactogenicity events occurred; most AE were mild. No serious AE related to vaccine occurred. A dose response effect was observed to F1, V and flagellin. The peak ELISA IgG antibody titers (95% CI) after two 10mcg doses of vaccine were 260.0 (102.6-659.0) and 983.6 (317.3-3048.8), respectively, against F1 and V antigens. The 6mcg dose group provided similar titers. Titers were low for the placebo, 1mcg and 3mcg recipients. A positive antibody dose response was observed to F1, V and flagellin. Vaccine antigen specific serum IgE was not detected. There were no significant rises in serum or cellular cytokine responses and no significant IgG increase to flagellin after the second dose. CONCLUSION: The Flagellin/F1/V vaccine exhibited a dose dependent increase in immunogenicity and was well tolerated at all doses. Antibody specific responses to F1, V and flagellin increased as dose increased. Given the results from this trial, testing higher doses of the vaccine may be merited.

Immunogenicity and safety of subunit plague vaccine: A randomized phase 2a clinical trial.

BACKGROUND: Although the killed whole-cell and live attenuated plague vaccine have been licensed, they are rarely used today because of toxicities, limited evidence of efficacy against plague, poor immune persistence required booster immunization every year, and limited commercial availability. This study was a randomized phase 2a clinical trial aimed to evaluating the immunogenicity and safety of a novel subunit plague vaccine. METHODS: 240 healthy adults aged 18-55 y were enrolled and randomly assigned at a ratio of 1:1 to receive 2 doses of 15 or 30 mcg vaccine at a 28-day interval between doses. Blood samples were collected at day 0, 28 and 56. Adverse events were collected during the first 28 d after each vaccination. Serious Adverse Event was observed throughout the study period. RESULTS: 239 participants received the first dose at day 0 and 238 received the second dose at day 28. Antibodies to envelope antigen faction 1 (F1) and recombinant virulence antigen (rV) were increased at day 28, and boosted significantly at day 56. For anti-F1 antibodies, geometric mean titer (GMT) and geometric mean fold increase (GMFI) were significantly higher in 30 mcg group than in the 15 mcg group(each P1< 0.05 at day 28 and each P1< 0.001 at day 56), with similar seroconversion rate of antibodies between 15 and 30 mcg group at both of the 2 time points. For anti-rV antibodies, seroconversion rate at day 28 in 30 mcg group was higher than that in 15 mcg group. However, GMT and GMFI of anti-rV antibodies were increased to approximately the same levels in the 2 groups. Similar booster immune response was also noticed in both groups at day 56. The injections were well tolerated, with mainly mild or moderate local and systemic adverse reactions (lower than grad 3). The proportion of pain at injection site was higher in 30 mcg group. None of SAEs were reported during 56 d. CONCLUSION: The plague vaccine comprised of F1 and rV antigens showed good safety and immunogenicity in adults aged 18-55 y old. The data show that the 30 mcg formulation is generally more immunogenic than the 15 mcg formulation, and represents the preferred formulation for further clinical development. It will be important to evaluate the long-term efficacy for appropriate formulations of the plague subunit vaccine.

Apparent field safety of a raccoon poxvirus-vectored plague vaccine in free-ranging prairie dogs (Cynomys spp.), Colorado, USA.

Prairie dogs (Cynomys spp.) suffer high rates of mortality from plague. An oral sylvatic plague vaccine using the raccoon poxvirus vector (designated RCN-F1/V307) has been developed for prairie dogs. This vaccine is incorporated into palatable bait along with rhodamine B as a biomarker. We conducted trials in August and September 2012 to demonstrate uptake and apparent safety of the RCN-F1/V307 vaccine in two prairie dog species under field conditions. Free-ranging prairie dogs and other associated small rodents readily consumed vaccine-laden baits during field trials with no apparent adverse effects; most sampled prairie dogs (90%) and associated small rodents (78%) had consumed baits. Visual counts of prairie dogs and their burrows revealed no evidence of prairie dog decline after vaccine exposure. No vaccine-related morbidity, mortality, or gross or microscopic lesions were observed. Poxviruses were not isolated from any animal sampled prior to bait distribution or on sites that received placebo baits. We isolated RCN-F1/V307 from 17 prairie dogs and two deer mice (Peromyscus maniculatus) captured on sites where vaccine-laden baits were distributed. Based on these findings, studies examining the utility and effectiveness of oral vaccination to prevent plague-induced mortality in prairie dogs and associated species are underway.

Live-attenuated Yersinia pestis vaccines.

Plague caused by Yersinia pestis is one of the most dangerous infectious diseases. There is no ideal plague vaccine available for human use, but a number of licensed killed whole-cell and live-attenuated vaccines have been available in the past. Currently, there are a number of vaccines under development, including live-attenuated, DNA and subunit vaccines, among others. This review deals with the development of live-attenuated plague vaccines. Traditionally, live-attenuated plague vaccines have been developed by multiple passages of fully virulent Y. pestis, but they have not gained general acceptance due to safety concerns. Recent attempts to construct attenuated Y. pestis strains with specifically defined mutations have opened the door for developing new candidates for live-attenuated plague vaccines, with a proper balance between safety and protective efficacy.

Current challenges in the development of vaccines for pneumonic plague.

Inhalation of Yersinia pestis bacilli causes pneumonic plague, a rapidly progressing and exceptionally virulent disease. Extensively antibiotic-resistant Y. pestis strains exist and we currently lack a safe and effective pneumonic plague vaccine. These facts raise concern that Y. pestis may be exploited as a bioweapon. Here, I review the history and status of plague vaccine research and advocate that pneumonic plague vaccines should strive to prime both humoral and cellular immunity.

Combating high-priority biological agents: What to do with drug-allergic patients and those for whom vaccination is contraindicated?

The threat of bioterrorism continues to be a very real one. Regularly, there are news stories on bioterrorism-related topics: What biologic weapons will our enemies likely use to attack the United States? How prepared is our country to successfully counter such attacks? Although these critical questions are being addressed by the leaders of our country, allergists-immunologists, too, will have to grapple with difficult questions during these uncertain and frightening times. We care for a special group of patients with various allergic and immunologic disorders. Some of our patients have immunodeficiency disorders that might preclude them from receiving life-saving vaccines. Our patients with drug allergies are fearful that should they become infected with a biologic agent, they will not be able to receive appropriate treatment. In this article we focus on the various vaccine-related and antibiotic-related adverse effects that the allergist-immunologist might see during treatment of infections caused by Category A agents. Where possible, potential management approaches are outlined.

Sterile abscess formation following plague vaccination.

As part of the immunisation programme of servicemen on OP Granby, deployed in the Gulf, plague vaccine was recommended as a prophylaxis. Out of a total of 524 vaccinations at our location, one sterile abscess formation was noted. The case report is described.

Prevention of plague: recommendations of the Advisory Committee on Immunization Practices (ACIP).

These revised recommendations by the Advisory Committee on Immunization Practices concerning prevention of plague update previous recommendations (MMWR 1982;31:301-4). This report includes information and recommendations on vaccination, public health practices, and medical treatment to prevent plague among humans.

[Combined (associated) vaccination against quarantinable infections]. / Kompleksnaia (assotsiirovannaia) vaktsinatsiia protiv karantinnykh infektsii.

The presence of several active foci of infection of different etiology is an indication for complex (combined) immunization against these diseases. The scheme of complex (combined) immunization against plague, cholera and yellow fever has been experimentally substantiated and successfully tested on volunteers.

[Combined (associated) immunization against typhoid, typhus and plague]. / Kompleksnaia (assotsiirovannaia) immunizatsiia protiv briushnogo i sypnogo tifov i chumy.

The article substantiates epidemiological expediency of complex (associated) immunization of servicemen and population against typhoid, typhus and plague in polyetiological zones of these infections, and also in cases of simultaneous proliferation of these diseases. For simultaneous preventive vaccination against these infections a complex immunization scheme was experimentally substantiated and clinically approved. It is based on national commercial vaccines and ensures a simultaneous administration of 2-3 vaccine preparations by hypodermic syringe or jet injection. Typhoid and typhus vaccines are injected under one shoulder-blade, and plague vaccine is injected under another shoulder-blade. This complex vaccine is harmless, moderately reactogenic, develops expressing immunity which have the same protective features as monovaccines alone. This scheme is recommended for use in anti-epidemic practice.

[Individual human personality characteristics as a factor in the etiology of postvaccinal reactions]. / Individual'no-lichnostnye osobennosti cheloveka kak faktor étiologii postvaktsinal'nykh reaktsii.

Healthy volunteers with quite opposite emotional properties defined by means of Cattell Personality Questionnaires were shown to have essential differences in their postvaccinal reactions. These differences were seemingly caused by psychoemotional tension developing in unstable persons as a result of their perception of vaccination as a threatening factor. The administration of Phenasepam (3 mg) decreased such emotional tension and thus removed negative reactions at the postvaccinal period. The preparation had no influence on the production of protective antibodies to all types of antigens used for immunization.

[Morphological study of the damaging effect of an EB vaccine strain of the plague microbe in inbred mice]. / Morfologicheskoe izuchenie povrezhdaiushchego deistviia vaktsinnogo shtamma EB chumnogo mikroba u inbrednykh myshei.

The data obtained during the study of the morphological changes in the internal organs and blood of 6 mouse strains at the early stages of anti-plague immunity are presented. It has been established that the introduction of 5.10(3) and 1.10(5) m. b. of the EV vaccine strain resulted in the development of morphological changes typical of residual virulence. The degree of these changes depended on the haplotype of the animals and the dose used. The most resistant to injury induced by EV strain were CBA mice (haplotype H-2k) and the most sensitive were C57BL/6 mice (haplotype H-2b).