A Phase 2b Randomized, Single-Blinded Study to Evaluate the Safety and Immunogenicity of 80 µg Recombinant Plague Vaccine (rF1V) With and Without Adjuvant at Two Vaccination Schedules in Healthy Adult Volunteers

Multicenter, randomized, single-blinded comparison of two formulations of the rF1V vaccine at a single dosage of 80 µg and two 3-dose schedules in 400 healthy, adult volunteers in four parallel cohorts. Two rF1V vaccine cohorts (N=160 each) and two rF1V antigen-only cohorts (N=40 each) will be vaccinated at two different three-dose schedules (Days 0, 56 and 182 or Days 0, 56 and 121).

开始日期2010-07-01

申办/合作机构

DynPort Vaccine Co. LLC

NCT00332956 / Completed临床2期

A Phase 2 (a), Dose-Blinded, Block-Randomized, Dose and Schedule Selection Study to Evaluate the Immunogenicity and Safety of the Recombinant Plague Vaccine rF1V in Healthy Volunteers

This Phase 2(a) clinical trial is designed as a dose-blinded, block-randomized, multi-center study to select a dosage and schedule of rF1V vaccine for further studies based on the immune response up to Day 210. Additional immunogenicity and safety/reactogenicity data will be collected through Day 540. Selection of dosage and schedule will be based on GMCs and seroconversion rates for anti-F1, anti-V and anti-rF1V antibody titers. Approximately 400 healthy adult volunteers will be enrolled (100 per group) in this study.

开始日期2006-05-01

申办/合作机构

DynPort Vaccine Co. LLC

NCT00097396 / Completed临床1期

A Phase 1, Open-Label, Dose-Escalating Study to Evaluate the Safety, Tolerability and Immunogenicity of the Recombinant Plague Vaccine rF1V in Healthy Volunteers

The purpose of this study is to evaluate the safety and tolerability of a two-dose schedule of the recombinant plague vaccine rF1V in healthy volunteers when given as an intramuscular (IM) injection at four ascending dose-levels. The purpose of the Cohort 4 Extension is to evaluate the safety and tolerability of a third intramuscular (IM) dose of 160 ug rF1V in healthy volunteers who have previously been vaccinated with the same concentration of rF1V vaccine.

开始日期2004-11-01

申办/合作机构

DynPort Vaccine Co. LLC

100 项与 Plague vaccine injectable(United States Army Medical Research Institute of Infectious Diseases) 相关的临床结果

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100 项与 Plague vaccine injectable(United States Army Medical Research Institute of Infectious Diseases) 相关的转化医学

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100 项与 Plague vaccine injectable(United States Army Medical Research Institute of Infectious Diseases) 相关的专利（医药）

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项与 Plague vaccine injectable(United States Army Medical Research Institute of Infectious Diseases) 相关的文献（医药）

2024-09-25·mSphere

Delivery of Yersinia pestis antigens via Escherichia coli outer membrane vesicles offered improved protection against plague

Article

作者: Wang, Yiqian ; Wu, Gengshan ; Tong, Zehui ; Zhang, Xiangting ; Yang, Ruifu ; Guo, Xiao ; Cao, Shiyang ; Meng, Xiangze ; Zhang, Yuan ; Wang, Tong ; Song, Yajun ; Du, Zongmin

ABSTRACT Outer membrane vesicles (OMVs) from Gram-negative bacteria can be used as a vaccine platform to deliver heterologous antigens. Here, the major protective antigens of Yersinia pestis, F1 and LcrV, were fused either with the leader sequence or the transmembrane domain of the outer membrane protein A (OmpA), resulting in chimeric proteins OmpA-ls-F1V and OmpA 46-159 -F1V, respectively. We show that OmpA-ls-F1V and OmpA 46-159 -F1V can be successfully delivered into the lumen and membrane of the OMVs of Escherichia coli, respectively. Mutation of ompA but not tolR in E. coli enhanced the delivery efficiency of OmpA-ls-F1V into OMVs. The OmpA-ls-F1V protein comprises up to 20% of the total protein in OMVs derived from the ompA mutant (OMV dA -ALS-F1V), a proportion significantly higher than the 1% observed for OmpA 46-159 -F1V in OMVs produced by an ompA mutant that expresses OmpA46-159-F1V, referred to as OMV dA -LATM5-F1V. Intramuscular ( i.m .) immunization of mice with OMV dA -ALS-F1V induced significantly higher levels of serum anti-LcrV and anti-F1 IgG, and provided higher efficacy in protection against subcutaneous ( s.c. ) Y. pestis infection compared to OMV dA -LATM5-F1V and the purified recombinant F1V (rF1V) protein adsorbed to aluminum hydroxide. The three-dose i.m . immunization with OMV dA -ALS-F1V, administered at 14-day intervals, provides complete protection to mice against s.c. infection with 130 LD 50 of Y. pestis 201 and conferred 80% against intranasal ( i.n .) challenge with 11.4 LD 50 of Y. pestis 201. Taken together, our findings indicate that the engineered OMVs containing F1V fused with the leader sequence of OmpA provide significantly higher protection than rF1V against both s.c . and i.n . infection of Y. pestis and more balanced Th1/Th2 responses. IMPORTANCE The two major protective antigens of Y. pestis , LcrV and F1, have demonstrated the ability to elicit systemic and local mucosal immune responses as subunit vaccines. However, these vaccines have failed to provide adequate protection against pneumonic plague in African green monkeys. Here, Y. pestis F1 and LcrV antigens were successfully incorporated into the lumen and the surface of the outer membrane vesicles (OMVs) of E. coli by fusion either with the leader sequence or the transmembrane domain of OmpA. We compared the humoral immune response elicited by these OMV formulations and their protective efficacy in mice against Y. pestis . Our results demonstrate that the plague OMV vaccine candidates can induce robust protective immunity against both s.c . and i.n. Y. pestis infections, surpassing the effectiveness of rF1V. In addition, immunization with OMVs generated a relatively balanced Th1/Th2 immune response compared to rF1V immunization. These findings underscore the potential of OMVs-based plague vaccines for further development.

2019-09-01·Vaccine3区 · 医学

Robust Th1 cellular and humoral responses generated by the Yersinia pestis rF1-V subunit vaccine formulated to contain an agonist of the CD137 pathway do not translate into increased protection against pneumonic plague

3区 · 医学

Article

作者: Shirwan, Haval ; Lawrenz, Matthew B ; Yolcu, Esma S ; Pulsifer, Amanda R ; Batra, Lalit ; Bowen, William

Yersinia pestis is the causative agent of plague and is a re-emerging pathogen that also has the potential as a biological weapon, necessitating the development of a preventive vaccine. Despite intense efforts for the last several decades, there is currently not a vaccine approved by the FDA. The rF1-V vaccine adjuvanted with Alhydrogel is a lead candidate subunit vaccine for plague and generates a strong Th2-mediate humoral response with a modest Th1 cellular response. As immune protection against Y. pestis requires both humoral and Th1 cellular responses, modifying the rF1-V subunit vaccine formulation to include a robust inducer of Th1 responses may improve efficacy. Thus, we reformulated the subunit vaccine to include SA-4-1BBL, an agonist of the CD137 costimulatory pathway and a potent inducer of Th1 response, and assessed its protective efficacy against pneumonic plague. We herein show for the first time a sex bias in the prophylactic efficacy of the Alhydrogel adjuvanted rF1-V vaccine, with female mice showing better protection against pneumonic plague than male. The sex bias for protection was irrespective of the generation of comparable levels of rF1-V-specific antibody titers and Th1 cellular responses in both sexes. The subunit vaccine reformulated with SA-4-1BBL generated robust Th1 cellular and humoral responses. A prime-boost vaccination scheme involving prime with rF1-V + Alhydrogel and boost with the rF1-V + SA-4-1BBL provided protection in male mice against pneumonic plague. In marked contrast, prime and boost with rF1-V reformulated with both adjuvants resulted in the loss of protection against pneumonic plague, despite generating high levels of humoral and Th1 cellular responses. While unexpected, these findings demonstrate the complexity of immune mechanisms required for protection. Elucidating mechanisms responsible for these differences in protection will help to guide the development of better prophylactic subunit vaccines effective against pneumonic plague.

2018-06-01·Vaccine3区 · 医学

A lipid A-based TLR4 mimetic effectively adjuvants a Yersinia pestis rF-V1 subunit vaccine in a murine challenge model

3区 · 医学

Article

作者: Ernst, Robert K ; Marshall, Jason D ; Yu, Li ; Gregg, Kelsey A ; Harberts, Erin ; Cayatte, Corinne ; Gardner, Francesca M ; Pelletier, Mark R ; McCarthy, Michael P

Vaccination can significantly reduce worldwide morbidity and mortality to infectious diseases, thereby reducing the health burden as a result of microbial infections. Effective vaccines contain three components: a delivery system, an antigenic component of the pathogen, and an adjuvant. With the growing use of purely recombinant or synthetic antigens, there is a need to develop novel adjuvants that enhance the protective efficacy of a vaccine against infection. Using a structure-activity relationship (SAR) model, we describe here the synthesis of a novel TLR4 ligand adjuvant compound, BECC438, by bacterial enzymatic combinatorial chemistry (BECC). This compound was identified using an in vitro screening pipeline consisting of (i) NFκB activation and cytokine production by immortalized cell lines, (ii) cytokine production by primary human PBMCs, and (iii) upregulation of surface costimulatory markers by primary human monocyte-derived dendritic cells. Using this SAR screening regimen, BECC438 was shown to produce an innate immune activation profile comparable to the well-characterized TLR4 agonist adjuvant compound, phosphorylated hexa-acyl disaccharide (PHAD). To evaluate the in vivo adjuvant activity of BECC438, we used the known protective Yersinia pestis (Yp) antigen, rF1-V, in a murine prime-boost vaccination schedule followed by lethal challenge. In addition to providing protection from lethal challenge, BECC438 stimulated production of higher levels of rF1-V-specific total IgG as compared to PHAD after both prime and boost vaccinations. Similar to PHAD, BECC438 elicited a balanced IgG1/IgG2c response, indicative of active T_H2/T_H1-driven immunity. These data demonstrate that the novel BECC-derived TLR4L adjuvant, BECC438, elicits cytokine profiles in vitro similar to PHAD, induces high antigen-specific immune titers and a T_H1-associated IgG2c immune titer skew, and protects mice against a lethal Yp challenge.

项与 Plague vaccine injectable(United States Army Medical Research Institute of Infectious Diseases) 相关的新闻（医药）

2022-09-12

·PRNewswire

Dynavax Announces First Participant Dosed in a Phase 2 Clinical Trial Evaluating an Adjuvanted Plague Vaccine

EMERYVILLE, Calif., Sept. 12, 2022 /PRNewswire/ -- Dynavax Technologies Corporation ( Nasdaq: DVAX), a commercial-stage biopharmaceutical company developing and commercializing innovative vaccines, in collaboration with the U.S. Department of Defense's (DOD) Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND) and supported by the DOD's Chemical and Biological Defense Program, today announced that the first participant has been dosed in a Phase 2 clinical trial evaluating the immunogenicity, safety, and tolerability of the JPEO-CBRND's Recombinant Plague (rF1V) vaccine combined with Dynavax's CpG 1018®adjuvant, in adults 18 to 55 years of age. "We are proud to support the U.S. government in developing an effective adjuvanted plague vaccine that we believe will allow U.S. service members to be protected with fewer doses administered over a shorter period of time," commented Ryan Spencer, Chief Executive Officer of Dynavax. "The development of a CpG 1018 adjuvanted plague vaccine is an important example of the broad utility of our adjuvant which we are leveraging to build our pipeline of new and improved vaccines." As previously announced, Dynavax and the DOD executed an agreement which provides for approximately $22 million in funding over two and a half years to develop an improved recombinant plague vaccine adjuvanted with CpG 1018 adjuvant. Under the agreement, Dynavax will conduct a Phase 2 clinical trial combining its CpG 1018 adjuvant with the DOD's rF1V vaccine. The trial is assessing a two-dose regimen administered over one month. Previous clinical studies of the rF1V, not including CpG 1018 adjuvant, have evaluated a three-dose regimen over six months. Any future commercial supply agreements would be subject to a separate agreement between Dynavax and the U.S government. About CpG 1018 Adjuvant Dynavax developed CpG 1018 adjuvant to provide an increased vaccine immune response with an improved tolerability profile, which has been demonstrated in HEPLISAV-B vaccine for adult hepatitis B and multiple COVID-19 vaccines that have received Emergency Use Authorization outside of the U.S. CpG 1018 adjuvant provides a well-developed technology and a significant safety database, potentially accelerating the development and large-scale manufacturing of novel or improved vaccines. About Dynavax Dynavax is a commercial-stage biopharmaceutical company developing and commercializing innovative vaccines to help protect the world against infectious diseases. The Company has two commercial products, HEPLISAV-B® vaccine [Hepatitis B Vaccine (Recombinant), Adjuvanted], which is approved in the U.S. and the European Union for the prevention of infection caused by all known subtypes of hepatitis B virus in adults 18 years of age and older, and CpG 1018® adjuvant, currently used in multiple adjuvanted COVID-19 vaccines. Dynavax is advancing CpG 1018 adjuvant as a premier vaccine adjuvant through global research collaborations and partnerships. Current collaborations are focused on adjuvanted vaccines for COVID-19, seasonal influenza, universal influenza, plague, shingles and Tdap. For more information about our marketed products and development pipeline, visit and follow Dynavax on LinkedIn. Forward-Looking Statements This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, which are subject to a number of risks and uncertainties. All statements that are not historical facts are forward-looking statements. Forward-looking statements can generally be identified by the use of words such as "anticipate," "believe," "continue," "could," "estimate," "expect," "forecast," "intend," "will," "may," "plan," "project," "potential," "seek," "should," "think," "will," "would" and similar expressions, or the negatives thereof, or they may use future dates. Forward-looking statements in this document include, without limitation, statements regarding our expectations as to outcomes relating to ongoing contractual relationships, the timing and potential outcomes of trials. These forward-looking statements are subject to assumptions, risks and uncertainties that may change at any time, and readers are therefore cautioned that actual results could differ materially from those expressed in any forward-looking statements. Factors that could cause actual results to differ include, among other things: risks and uncertainties associated with actual results of our clinical trials; whether and when an improved plague vaccine candidate will be approved for use and launched; whether we can manufacture sufficient quantities of CpG 1018 to support this program; and other risks and uncertainties discussed in the Company's filings with the SEC, including the "Risk Factors" sections of the Company's Quarterly Report on Form 10-Q for the quarter ended June 30, 2022. The Company undertakes no obligation to update any forward-looking statements as a result of new information, future developments or otherwise, except as expressly required by law. All forward-looking statements in this document are qualified in their entirety by this cautionary statement. Contacts: Nicole Arndt, Investor Relations and Corporate Communications [email protected] 510-665-7264 Derek Cole, President Investor Relations Advisory Solutions [email protected] SOURCE Dynavax Technologies

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100 项与 Plague vaccine injectable(United States Army Medical Research Institute of Infectious Diseases) 相关的药物交易

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