Track topics on Twitter Track topics that are important to you
The dose of recombinant MVA used in the TB trials to date is relatively low compared with other trials using recombinant MVAs which have used up to 2.5 x 108pfu (A Hill, personal communication). Having demonstrated safety and immunogenicity of 5 x 107pfu of MVA85A, we now need to perform a dose optimization study, prior to commencing larger scale Phase II and III studies in South Africa. We will vaccinate 12 volunteers with a dose half a log lower than the dose we are currently using, i.e. 107pfu MVA85A, and 12 volunteers with a dose half a log higher, i.e. 108pfu.
MVA85A (at a dose of 5 x 107pfu) has been administered to 41 healthy volunteers in the UK and 17 healthy volunteers in The Gambia, with no serious adverse events. We have designed our Phase I studies to allow for a vaccination of volunteer groups sequentially with a step-wise increase in mycobacterial exposure, in order to minimize the possibility of a Koch reaction. A Koch reaction describes the development of immunopathology in a person or animal with tuberculosis, when an exaggerated immune response to M.tb is stimulated. It was described in patients with TB disease when Koch performed his original studies employing mycobacteria as a type of therapeutic vaccination. It has now been demonstrated in the mouse model of therapeutic vaccination (Taylor, 2003). Available animal data suggest that these reactions do not occur in mice latently infected with M.tb, suggesting that such reactions may correlate with high bacterial load and that the Koch phenomenon may not pose a problem for vaccination of healthy albeit latently infected humans. We started these studies in healthy volunteers who were as mycobacterially naïve as possible. They were skin test negative and Elispot negative for PPD, ESAT 6 and CFP10, and had not had previously been vaccinated with BCG. We have now completed studies in the UK vaccinating volunteers previously vaccinated with BCG (McShane, 2004). These volunteers are excluded if their Mantoux test is greater than 15 millimeters. These studies are ongoing in The Gambia. The group we are currently recruiting for on this increasing mycobacterial spectrum are healthy volunteers who are latently infected with M.tb.
Decision matrix for selecting MVA85A dose
1. If reducing the dose of MVA85A results in reduced immunogenicity, we could use either the 5x107 or 108 dose, and would select the lower of these on the grounds of safety.
2. If increasing the dose of MVA85A increases the incidence of side-effects, we could use either the 5x107 or 107 dose, and we would use the higher of these on the grounds of immunogenicity.
3. If increasing the dose of MVA85A results in increased immunogenicity and no increase in side-effects, we could use either the 5x107 or 108 dose in subsequent trials
4. If reducing the dose of MVA85A results in no reduction in immunogenicity we could use either the 107 or 5x107 dose in subsequent trials
5. If all three doses are equally safe and immunogenic we will use either the low or 5x107 dose.
Allocation: Non-Randomized, Control: Uncontrolled, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention
University of Oxford, CCVTM, Churchill Hospital
University of Oxford
Published on BioPortfolio: 2014-08-27T03:38:55-0400
Tuberculosis is a major cause of mortality among AIDS patients in the developing world. The diagnosis of tuberculosis in HIV infected children is complicated by inefficient and expensive ...
The purpose of this study is to assess lung immune responses in patients with active pulmonary tuberculosis (TB) and in healthy control persons who are exposed to Mycobacterium tuberculosi...
The presence of M. tuberculosis in non-invasive throat swabs of patients withdrawn for suspected tuberculosis. Hypothesis 10% of patients infected by M. tuberculosis are carrier of M. tub...
Tuberculosis and vitamin D deficiency are important public health problems in India. Before the advent of effective antitubercular therapy, patients with tuberculosis were advised treatme...
The purpose of this study is to determine the better preoperative anti-tuberculosis treatment period of patients with spinal tuberculosis.
Hypercalcemia might present itself in association with granulomatous diseases such as tuberculosis. We report a rare case of a 62-year-old man with hypercalcemia due to hepatic tuberculosis. The diagn...
Tuberculosis (TB) still is a major worldwide health problem, with 10.4 million new cases in 2016. Only 5-15% of people infected with M. tuberculosis develop TB disease while others remain latently inf...
Multidrug-resistant tuberculosis poses a major threat to the success of tuberculosis control programs worldwide. Understanding how drug-resistant tuberculosis evolves can inform the development of new...
In Canada, tuberculosis disproportionately affects the foreign-born population. The national tuberculosis medical surveillance programme aims to prevent these cases. Individuals referred for further i...
Tuberculosis screening was performed for a healthy asymptomatic woman to determine whether she had been infected with active genital tuberculosis via sexual intercourse with her husband who had epidid...
The dormant form of TUBERCULOSIS where the person shows no obvious symptoms and no sign of the causative agent (Mycobacterium tuberculosis) in the SPUTUM despite being positive for tuberculosis infection skin test.
Tuberculosis of the brain, spinal cord, or meninges (TUBERCULOSIS, MENINGEAL), most often caused by MYCOBACTERIUM TUBERCULOSIS and rarely by MYCOBACTERIUM BOVIS. The infection may be limited to the nervous system or coexist in other organs (e.g., TUBERCULOSIS, PULMONARY). The organism tends to seed the meninges causing a diffuse meningitis and leads to the formation of TUBERCULOMA, which may occur within the brain, spinal cord, or perimeningeal spaces. Tuberculous involvement of the vertebral column (TUBERCULOSIS, SPINAL) may result in nerve root or spinal cord compression. (From Adams et al., Principles of Neurology, 6th ed, pp717-20)
Pathological conditions of the CARDIOVASCULAR SYSTEM caused by infection of MYCOBACTERIUM TUBERCULOSIS. Tuberculosis involvement may include the HEART; the BLOOD VESSELS; or the PERICARDIUM.
TUBERCULOSIS that involves any region of the GASTROINTESTINAL TRACT, mostly in the distal ILEUM and the CECUM. In most cases, MYCOBACTERIUM TUBERCULOSIS is the pathogen. Clinical features include ABDOMINAL PAIN; FEVER; and palpable mass in the ileocecal area.
Tuberculosis of the mouth, tongue, and salivary glands.
In a clinical trial or interventional study, participants receive specific interventions according to the research plan or protocol created by the investigators. These interventions may be medical products, such as drugs or devices; procedures; or change...
Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...
Alternative Medicine Cleft Palate Complementary & Alternative Medicine Congenital Diseases Dentistry Ear Nose & Throat Food Safety Geriatrics Healthcare Hearing Medical Devices MRSA Muscular Dyst...