Volunteers immunization clinics

Edelman R, Wasserman SS, Kublin JG, Bodison SA, Nardin EH, Oliveira GA, Ansari S, Diggs CL, Kashala OL, Schmeckpeper BJ, Hamilton RG. Immediate-type hypersensitivity and other clinical reactions in volunteers immunized with a synthetic multi-antigen peptide vaccine (PfCS-MAPlNYU) against Plasmodium falciparum sporozoites. Vaccine 2002 21(3-4) 269-80. 

Dooley KE, Park JG, Swindells S, Allen R, Haas DW, Cramer Y, et al. Safety, tolerability, and pharmacokinetic interactions of the antituberculous agent TMC207 (bedaquiline) with efaviienz in healthy volunteers AIDS Clinical Trials Group Study A5267. J Acquir Immune Defic Syndr 2012 59(5) 455-62. 

Research on an hCG vaccine has been conducted over the past 15 years. WHO has conducted a phase I clinical study in AustraUa, using a vaccine based on a synthetic C-terminal peptide (109—141) of P-hCG conjugated to Diptheria Toxoid (CTP-DT), that showed potentially effective contraceptive levels of antibodies were produced in vaccinated women without any adverse side effects. Phase II clinical studies are under consideration to determine if the immune response, raised to its prototype anti-hCG vaccine, is capable of preventing pregnancy in fertile women volunteers (115). While research on the C-terminal peptide from the P-subunit of hCG has been carried out under the auspices of WHO, research supported by the Population Council and the National Institutes of Health has involved two alternative vaccine candidates (109,116,118). 

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. 

The phase 1 clinical trial for HGB-30 consisted of 18 seronegative healthy volunteers (6/group) who were administered 10,20, or 50 pg of the vaccine at 0,6, and 14 weeks. Physical examinations and blood analyses were performed, and all subjects were followed for 1 year. Initial results indicated that the vaccine was not associated with any adverse effects. Similarly to that observed in mice and chimpanzees, antibodies to HGP-30 were observed in volunteers. Since T cell proliferative responses are considered to be optimal with fresh cells, extensive studies were carried out on one volunteer s peripheral blood lymphocytes. Increased T cell proliferation was observed. The T cell proliferation was maximal 6 weeks after the third immunization but then declined at 6 months after the third immunization. 

Volunteers can be the backbone of many essential functions at mass immunization and treatment clinics. The following is a listing of functions that volunteers can perform in these types of clinics. 

After influenza immunization there was a reduction in blood theophylline concentrations in patients and healthy volunteers (58). The authors concluded that flu vaccine may influence the pharmacokinetics of several drugs, and a second group found that theophylline oxidation was significantly reduced at 1 day, but not at 7 days, after immunization (57). However, others did not confirm these effects (55,59). The lack of a clinical interaction with theophylline has also been confirmed by a report of the US Immunization Practices Advisory Committee (9). 

During the initial Phase I, the basic safety features of the vaccine candidate are intensively studied in a Kmited number (<100) of patients or healthy volunteers. The main purpose of these studies is to confirm the vaccine s local and general tolerance before it is applied in further clinical trial subjects, but Phase I vaccine studies can partly be used for a first dosefinding, and immunological evaluations for adequate immune responses. During Phase I trials, vaccines rarely fail due to safety concerns, but quite frequently due to insufficient or inconsistent immune responses below expected levels. 

The true incidence of allergic sensitization due to cephalosporins alone is difficult to assess, since in most patients treated with cephalosporins, the immune status for penicillin sensitivity before treatment is not objectively known and assessed. The general clinical impression is that in patients sensitized to benzyl-penicillin, overt allergic clinical reactions do not occur in more than 10%-20% of those subsequently treated with cephalosporins. The rate of adverse reactions may, however, be higher than suspected. In healthy volunteers given cephalothin and ce-phapirin intravenously, an unexpectedly high rate of reactions was experienced, and five patients developed skin hypersensitivity detected by skin test with PPL. 

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