Subject vaccines

Cross, A.S., Opal, S.M., Palardy, J.E., Drabick, J.J., Warren, H.S., Huber, C., Cook, P., Bhattacharjee, A.K. Phase I study of detoxified Escherichia coli 35 lipopolysaccharide (J5dLPS)/group B meningococcal outer membrane protein (OMP) complex vaccine in human subjects. Vaccine 21 (2003) 4576-4588. 

The diseases to which poultry are subject are legion (Sainsbury, 1992). However, he does make the point that if vaccines and medicines were not so freely available, which they are not for organic producers, then... 

The safety of the cocaine vaccine TC-CD in former cocaine abusers has been evaluated in a Phase I clinical trial, and it was determined that the vaccine was well tolerated with dose-related increases in antibody levels.65 Two Phase II clinical trials have now been conducted.66,67 The vaccine was again well tolerated and subjects reported a reduction in cocaine s reinforcing effects. The antibody levels were detectable after the second dose, peaked at 8 to 12 weeks, and remained elevated for up to 6 months preliminary findings indicated a negative association between antibody level and cocaine use. Other anti-cocaine vaccines in development include a blocking antibody (ITAC-cocaine) and a monoclonal catalytic antibody (15A10). 

The conventional rabies vaccine was administered to the nine initially naive subjects seven days after completing the oral vaccination. Three of these volunteers produced neutralizing antibodies against rabies virus, although none of the five control subjects did. This study showed a clear indication that the orally delivered rabies vaccine has potential as an oral booster for the conventional rabies vaccine. 

Generalized vaccinia Secondary lesions of the skin following vaccination which may occur in subjects with previously healthy skin but are more common in the case of traumatized skin, especially in the case of eczema(eczema vaccinatum). In the latter instance, generalized vaccinia may result from mere contact with a vaccinated person. Secondary vaccinial lesions may also occur following transfer of virus from the vaccination to another site by means of the fingers (autoinnoculation). 

Regulatory guidance for the conduct of clinical trials on vaccines is specific. Traditional phase I trials in normal volunteers are not conducted. Rather, all trials assess not only safety but also efficacy (or at least immunogenicity). Trials may well be challenge trials, that is, after immunization subjects are purposely challenged with exposure to the infective agent of concern. 

In any case, injection site responses (erythemia, edema, pain, and tenderness) and systemic responses are both evaluated in subjects (Mathieu, 1997). USFDA also has specific guidance on the tracking and reporting of adverse clinical responses to vaccines. Any adverse events or product problems with vaccines should not be sent to MedWatch but to the Vaccine Adverse Event Reporting System (VAERA), operated jointly by FDA and the national Centers for Disease Control and Prevention. For a copy of the VAERS form, call 1-800-822-7967, or download the form (in PDF format) from www.fda.gov/cber/vaers/vaersl.pdf on FDA s Website. 

The immune response of Gardasil was evaluated in 8915 women from 18 to 26 years of age (Gardasil N = 4666, placebo N = 4249) and 2054 adolescents from 9 to 17 years of age (Gardasil = 1471,placebo 583). Overall,more than 99.5% of the subjects were seropositive with antibodies against HPV 6, HPV 11, HPV 16, and HPV 18. The table below shows the levels of antibodies with and without Gardasil vaccination. 

Quantitative entrapment of vaccines into small (up to about 200 nm diameter) liposomes in the absence of microfluidization (which can damage DNA and other labile materials when extensive) can be carried out by a novel one-step method (7) as follows SUVs (e.g., cationic) prepared as in section Preparation of Small Unilamellar Vesicles are mixed with sucrose to give a range of sucrose-to-lipid weight/weight ratio of 1.0 to 5.0 and the appropriate amount of plasmid DNA (e.g., 10-500 pg) and/or protein (e.g., up to 1 mg). The mixture is then rapidly frozen and subjected to dehydration by freeze-drying, followed by rehydration as in section Preparation of Vaccine-Containing Dehydration-Rehydration Vesicles. ... 

The content of vaccine within the small liposomes is estimated as in the section Estimation of Vaccine Entrapment in Dehydration-Rehydration Vesicles Liposomes for both microfluidized and sucrose liposomes and expressed as percentage of DNA and/or protein in the mixture subjected to freeze drying as in the section Preparation of Vaccine-Containing Small Liposomes by the Sucrose Method in the case of sucrose small liposomes or in the original DRV preparation (obtained in the section Estimation of Vaccine Entrapment in DRV Liposomes ) for microfluidized liposomes. Vesicle size measurements are carried out by PCS as described elsewhere (6,8,17). Liposomes can also be subjected to microelectrophoresis in a Zetasizer to determine their zeta potential. This is often required to determine the net surface charge of DNA-containing cationic liposomes. 

Furthermore, by comparing the gene expression profdes of healthy clinical subjects with those clinical subjects who experienced adverse reactions after administration of the vaccine, it will be possible to find differences in their immune responses and to identify biomarkers for these adverse reactions. These biomarkers can then be utilized in future vaccine development, diagnosis, and risk calculations. 

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