Vaccine clinical testing

Another future area of research for monitoring adverse reactions to food additives might involve the development of clinical tests to screen for genetic biomarkers indicating food sensitivities. Perhaps vaccines will be developed and administered to sensitive individuals, preventing the occurrence of adverse reactions from food additives. 

Alzheimer s Disease The vaccine being tested contains a small protein called jS-amyloid (AjS). This protein forms abnormal deposits, or plaques, in the brains of people with Alzheimer s disease. Researchers believe that Kji deposition causes loss of mental function by killing the brain neurons. The strategy of Aji vaccination is to stimulate the immune system to clean up plaques and prevent further A deposits. Although preclinical and Phase I studies showed the potential of the vaccine, the Phase II clinical trial was halted because 15 of 360 patients developed severe brain inflammation. Further studies showed that the A did generate the desired... 

Bunyak, E.B. Hilleman, M.R. Weiber, R.E. Stokes, J., Jr. Live attenuated rubella virus vaccines prepared in duck embryo cell culture. I. Development and clinical testing. J. Am. Med. Assoc. 1968, 204, 195-200. 

Van der Laan JW, Forstor R, Ledwith B, Gruber M, Gould S, Penninks A. Non clinical testing of vaccines Report from a workshop. Drug Inf J. 2009 43 75-85. 

Tang RS, Spaete RR, Thompson MW, MacPhail M, Guzzetta JM, Ryan PC, Reisinger K, Chandler P, Hilty M, Walker RE, Gomez MM, Losonsky GA. Development of a PIV-vectored RSV vaccine Preclinical evaluation of safety, toxicity and enhanced disease and initial clinical testing in healthy adults. Vaccine. 2008 26 373-6382. 

Preclinical Results and Clinical Applications. Both pDNA- and mRNA-based vaccinations were demonstrated to be efflcacious in animal models as prophylactic or therapeutic immunotherapies against tumors, infectious diseases, and allergy. Two pDNA-based vaccines are commercialized for veterinary use an anti-equine fever and an anti-infectious hematopoietic necrosis virus (IHNV) for farm-raised salmons. In humans, several formulations of nucleic acid vaccines are tested in clinical trials (see the actualized list of trials at www.clinicaltrials.gov). Although pDNA-based vaccine trials were reported in the context of antitumor, antivirus (HIV, influenza virus, HBV) and antiparasite Plasmodium falciparum) approaches, mRNA-based vaccines were up to now tested only as immunotherapies against cancer (review by Liu and Ulmer for pDNA [35] and Pascolo for mRNA [36]). 

Before a new vaccine is tested in clinical trials, a reasonable set of data should be accumulated to provide evidence that... 

Because of the declining potency of the existing smallpox vaccines and continued concerns about the prospect of the use of variola virus in biological warfare, a new vaccinia vaccine is in clinical testing by the U.S. Army Medical Research and Materiel Command, Fort Detrick, Frederick, Maryland. This vaccine was derived from a NYCBOH strain of vaccinia and then produced in human diploid lung fibroblast cell cultures. Unlike calf-lymph vaccines, this cell culture-derived vaccinia vaccine contains no adventitious agents. 

As of 1995, there were 79 new, non-AIDS-related anti-infective drugs and vaccines. 28 of which were antibiotics, in development by 49 different U.S. companies (4). Additionally, 103 medicines and vaccines are currently in development for AIDS arnJ AIDS-related opportunistic infections (4). Table 3 lists a few promising anti-jnfective agents that are currently in clinical testing or that have recently entered the commercial market. A few of these are discussed in more detail in this section. 

Until now only the saponin adjuvant QS-21 (3) has entered vaccine clinical trials. Saponin mixtures causing local toxicity and hemolytic activity such as Quil A, have not yet been tested in clinical trials of human vaccines. After preclinical trials of QS-21 in rabbits, dogs, rhesus monkeys and baboons, this molecule was evaluated in phase 1 clinical trials of experimental melanoma immunotherapeutic vaccines, of HIV-1 subunit vaccines and more recently of a promising malaria vaccine [34-36]. 

Once a suitable strain is available, the prachce is to grow, often ftom a single organism, a sizeable culture which is distributed in small amounts in a large number of ampoules and then stored at 70°C or freeze-dried. This is the seed lot. From this seed lot, one or more ampoules are taken and used as the seed to originate a limited number of batches of vaccine which are first examined exhaustively in the laboratory and then, if found to be satisfactory, tested for safety and efficacy in clinical trials. Satisfactory results in the clinical trials validate the seed lot as the seed from which batches of vaccine for routine use can subsequently be produced. 

Because of the risks of adverse reaction to the vaccine by persons who had already been exposed to the disease a sensitivity test must be carried out prior to immunization with BCG. A Mantoux skin test assesses an individual s sensitivity to a purified protein derivative (PPD) prepared fi om heat-treated antigens (tuberculin) extracted fiom M tuberculosis. A positive test imphes past infection or past, successful immunization Those with strongly positive tests may have active disease and should be referred to a chest clinic. Many people with active TB, especially disseminated TB, however, sero-convert fiom skin test positive to skin test negative. Results of the skin test must therefore be interpreted with care. 

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