(CIR) is a leader in vaccine evaluation and Good Clinical Practice (GCP) training.
Established in 1985 by Dr. Mary Lou Clements-Mann, the CIR is one of the nation’s leading vaccine research centers.
CIR investigators primarily conduct Phase I and II clinical trials of new vaccine candidates in the U.S. and in less-developed countries.
The CIR has also achieved international recognition for its capacity to train other research professionals to develop the skills and infrastructure needed to design and conduct clinical vaccine trials, with a focus on applied GCP.
The experienced personnel and facilities of the CIR serve as major resources for vaccine research at the Johns Hopkins University and around the globe.
In a commentary on the biosecurity controversy surrounding publication of bird flu research details, a bioethicist and a vaccine expert at Johns Hopkins reaffirm that "all scientists have an affirmative ethical obligation to avoid contributing to the advancement of biowarfare and bioterrorism," but that there are not sufficient structures in place to evaluate potential societal risks. Authors Ruth R. Faden, Ph.D., and Ruth A. Karron, M.D., say "adequate assessment of those risks requires "prospective review by an international body with a range of expertise, including in this case influenza virology and biosecurity."
Read the full article in the journal Science:
On July 14th, 2010 the flavivirus research team at the Center for Immunization Research (CIR), led by Dr. Anna Durbin, launched a phase I clinical trial of a novel tetravalent vaccine, TetraVax-DV, designed to prevent dengue fever. Dengue virus is a member of the flavivirus family, which also includes yellow fever, St Louis encephalitis and West Nile viruses. Dengue virus causes dengue fever, and also the more severe form of the disease, dengue hemorrhagic fever (DHF). Together, dengue fever and dengue hemorrhagic fever cases occur in more than 50 million people annually, predominantly in Asia, Africa and Latin America. A vaccine against this mosquito-borne virus would protect and improve lives around the world.
Studies of the first tetravalent formulation were initiated in July 2010 and preliminary results from the evaluation of all formulations are expected by December 2010. Following testing of the tetravalent vaccine candidates in Baltimore and with colleagues at the University of Vermont, clinical trials are expected to begin in Brazil in early 2011. The Instituto Butantan has licensed the vaccine for production in Brazil and is planning the construction of a vaccine production facility for the live-attenuated dengue vaccine. Such a vaccine could have immense programmatic utility for large-scale vaccine programs around the world. For more information, contact Dr. Anna Durbin at email@example.com or visit the Center for Immunization Research.
Enteric Vaccine Research
Recently, the CIR Enteric Vaccine Research Unit (EVRU) completed a triad of studies to evaluate the safety, immunogenicity and efficacy of a novel live-attenuated ETEC vaccine. The first study initiated in early 2009 aimed to refine a well-established ETEC human challenge model. In a human challenge model, a well-characterized strain of a pathogen is administered to volunteers according to standardized procedures in order to achieve a consistent and reproducible illness attack rate. Once a challenge model is established it can be used to evaluate vaccines or other interventions aimed at preventing or treating illness resulting from exposures to a given pathogen or family of pathogens. The goal of our ETEC challenge refinement study was to alter certain key conditions in the model to enable administration of a lower dose of bacteria and yet still induce an attack rate comparable to that achieved using higher inoculum doses. This is important because there has been some concern voiced in past years that potential vaccine candidates could have been overwhelmed by an artificially high challenge inoculum, thereby prematurely truncating the development pathway for nascent vaccines. Upon completion of the 55-subject ETEC challenge model refinement study, we were able to adjust the model in a way that enabled us to obtain an attack rate of >70% while reducing the standard inoculum by 2 logs. By lowering the challenge dose, the hope was to more closely approximate natural exposures in endemic areas, and to provide an opportunity to gain a “sneak peak” at vaccine efficacy and potential immune correlates prior to embarking on large-scale field trials.
Following the ETEC challenge model refinement study, in the second half of 2009 we embarked on a Phase I dose-escalation study of a novel genetically engineered live-attenuated ETEC vaccine called ACE527. In this study, 18 subjects received 2 oral doses of ACE527 (109 colony forming units (cfu) or placebo given 3 weeks apart. Upon determining that this dose was well tolerated, another 18 subjects received 2 oral doses of ACE 527 (1010 cfu) or placebo. This higher dose was also well tolerated. These results paved the way for the initiation in the 2nd quarter of 2010 of a 70-subject proof-of-concept study to expand our understanding of the safety, tolerability and immunogenicity of ACE527, and to see if the vaccine induced protection against a highly virulent ETEC challenge strain called H10407. Subjects were recruited and enrolled over an 8 week recruitment period. Half of these subjects received ACE527 (1010 cfu) in 2 doses given 3 weeks apart and half the subjects received a placebo preparation in similar fashion. One month after the 2nd dose of vaccine or placebo, subjects were admitted to our Inpatient Unit for the 10-day challenge portion of the study. On the day following admission, all subjects were challenged with the same dose of ETEC strain H10407 that was evaluated in the ETEC challenge model refinement study described above. The clinical portion of the study was completed at the end of August 2010. The study is now in the data analysis phase and results are anticipated in early 2011. For more information, contact Dr. Clayton D. Harro at firstname.lastname@example.org or visit the Center for Immunization Research.
H1N1 Clinical Trials
In August 2009, the Center for Immunization Research (CIR) at the Johns Hopkins Bloomberg School of Public Health was selected by CSL Biotherapies of Australia to be the lead site of one of the largest H1N1 vaccine trials. Eleven sites throughout the US enrolled over 1300 volunteers, 55 of whom were enrolled at the CIR. The study goals were to measure the safety and immunogenicity of CSL’s H1N1 influenza vaccine given at three separate dosing levels (7.5 mcg, 15 mcg, and 30 mcg of influenza hemagglutinin antigen [HA]) versus placebo. Two groups of participants were enrolled in the trial: adults 18 to 64 and adults older than 65. Both groups received two injections of vaccine or placebo three weeks apart. Laboratory evaluations were conducted at 3 and 6 weeks after the first vaccination to check for antibodies for H1N1.
Older subjects, especially those 75 years and older, were more likely to have pre-existing antibodies to the 2009 H1N1 influenza prior to vaccination than were younger adult subjects. "The vaccine was found to be well tolerated, with adverse events that were predominantly mild or moderate in nature, and similar to those seen after seasonal influenza. We found that the 2009 H1N1 vaccine to be highly immunogenic, even at the lowest dose tested of 7.5-mcg HA (this is half the dose of each component of the seasonal trivalent influenza vaccine). It was also highly immunogenic in elderly adults, more than what would be expected based on studies of seasonal influenza vaccine in the elderly. The results of this trial have been published in the Journal of Infectious Diseases:
Talaat, KR, Greenberg, ME, Lai, MH, Hartel, GF, Wichems, CH, Rockman, S, Jeanfreau, RJ, Ghosh, MR, Kabongo ML, Gittleson, C and Karron, RA. A single dose of unadjuvanted novel 2009 H1N1 vaccine is immunogenic and well tolerated in young and elderly adults
For more information, contact Dr. Kawsar Talaat at email@example.com or visit the Center for Immunization Research.
We are currently conducting clinical trials for respiratory viruses, malaria, dengue virus, and traveler's diarrhea