ClinicalRM has over 20 years developing and testing vaccines and vaccine products. We have been involved in over 225 clinical trials of which 115 were vaccine trials. We have accrued over 17,000 subjects for trials of all types. This is our story.
Before a vaccine can be developed there needs to be information regarding the incidence and prevalence of a disease. ClinicalRM is significantly involved in surveillance both here in the U.S. and OCONUS. We provide services that impact the DoD Global Emerging Infections Systems (GEIS) programs and Threat Agent Detection and Response (TADR) system in multiple OCONUS countries. Data from these and other sources will determine what vaccines are needed to be developed to protect our Military personnel as well as civilian populations. Services provided by ClinicalRM include the identification of agents on site or sent back to our laboratory personnel at WRAIR and elsewhere for confirmatory identification. Data on a new agent is accrued and plotted to determine high-risk populations using temporal indices, duration, and transmission intensity methodology, as well as spatial statistics with computer modeling/GIS data. Survey data will be collected from subjects to determine the past history of agent contact and other pertinent data. Such information is not only useful for vaccine development planning but also for site determination for clinical trials. At the same time our research personnel utilize the latest technology to understand the biochemical and biophysical makeup of the agent.
Our vaccinologists will utilize multiple techniques to develop vaccines against the infectious agent. These may include using live, attenuated agents, weakened by any of several techniques. An example of such a vaccine is a live attenuated dengue vaccine tested by ClinicalRM personnel at the WRAIR CTC. Another vaccine tested by our personnel at the CTC is the RTS, S malaria vaccine. We have provided a number of clinical trials for this series of vaccines. It is interesting in that the vaccine was engineered using genes from the repeat and T-cell epitope in the circumsporozoite protein (CSP) of Plasmodium falciparum malaria parasite and a viral envelope protein of the hepatitis B virus (HBsAg) and a chemical adjuvant to boost the immune system response. CSP is a protein excreted by the sporozoite stage of malaria. The antibodies produced by the vaccine inhibit the liver stage of the malaria parasite. The RTS,S vaccine was developed by GlaxoSmithKline (GSK). Various testing including challenge studies using infected mosquitoes was performed at the CTC with ClinicalRM personnel. Vaccines can also be killed or inactivated. One such example tested by ClinicalRM personnel was an inactivated vaccine for Japanese Encephalitis (JE-PIV).
Some vaccines are produced by fractionating the infectious agent and using only a portion of the agent that does not cause disease. ClinicalRM personnel were involved in the development and testing of a Group B Meningococcal Outer Membrane Protein Vesicle vaccine. In this vaccine’s development only the outer membrane of the bacterium was isolated. This component, although not infectious in itself, will stimulate an immune response to the whole infectious agent. ClinicalRM personnel have been involved in developing vaccines against malaria, dengue, HIV, adenovirus, influenza, and bacteria such as Shigella and various meningitis agents, among others.
Although most of us think of a vaccine as being administered by injection into the arm or other site, there are a number of vaccines administered by other methods. ClinicalRM personnel have been involved in studies of the oral and nasal administration of vaccines. Most people are familiar with the oral Sabin polio vaccine. ClinicalRM has been involved in the clinical evaluation of microencapsulated CS6 vaccine for enterotoxigenic Escherichia coli (ETEC) diarrhea administered via the oral route. As most people with allergies know, the nasal passage is a very powerful site of immunologic response. It is not surprising that this route of vaccine administration has been used for certain vaccines. ClinicalRM has been involved in Phase I studies of the nasal administration of influenza vaccine for the National Institute of Allergy and Infectious Diseases (NIAID).
After a clinical trial is completed, the work is not done. Samples of blood and other specimens will usually be collected and sent to the laboratory to determine how immunogenic the vaccine is, the proper dose and whether the vaccine is safe and effective. ClinicalRM personnel provide complete clinical trials services for vaccine development.
Eventually all the basic research data, pre-clinical and clinical trials data must be reviewed by FDA. ClinicalRM assists customers in this process. We are a full-service CRO.