Vaccine interference

An unresolved problem with the use of TC-83, and presumably with other live-attenuated alpha-virus vaccines, is the phenomenon of vaccine interference, in which prior immunity to heterologous alphaviruses inhibits vaccine virus replication and subsequent immune responses. This occurrence has been observed in horses,169 170 in which preexisting antibodies to EEE and WEE may have interfered with TC-83 vaccination. Interference has also been observed in humans, in whom prior vaccination with Chikungunya virus has reduced the response to TC-83, and vice versa (D.J.McC., unpublished research, 1994). 

Vaccinations containing live organisms are not administered within 3 months of immune globulin administration because antibodies in the globulin preparation may interfere with the immune response to the vaccination. Corticosteroids, antineoplastic dru, and radiation therapy depress the immune system to such a degree that insufficient numbers of antibodies are produced to prevent the disease. When the salicylates are administered with the varicella vaccination, there is an increased risk of Reye s syndrome developing. 

Antibodies in the immune globulin preparations may interfere with the immune response to live virus vaccines, particularly measles, but also others, such as mumps and rubella It is recommended that the live virus vaccines be administered 14 to 30 days before or 6 to 12 weeks after administration of immune globulins. No known interactions have been reported with antivenins. 

Many factors have to be considered when developing combination vaccines. First the selected components need to be given on a similar schedule and all components should already be licensed in the United States. The excipients contained in the individual vaccines may interfere with another component when combined, altering a component s immunogenicity. Finally, the immunogenicity of the combination must be similar (within 10%) to the immune response when the components are administered separately. This has been problematic with combinations containing Haemophilus influenza type b vaccine, for which the immune response has been significantly blunted in some combinations.13... 

Up to 500 pg of plasmid DNA (for the amount of PC shown above) is dissolved in 2mL distilled water, or lOmM sodium phosphate buffer (PB) of pH 7.2 if needed. For liposomes containing both the plasmid DNA and the vaccine protein it encodes (or only the protein), up to 1 mg of the protein is included. The nature of buffer with respect to composition, pH, and molarity can be varied as long as this does not interfere with liposome formation or DNA and protein entrapment yield. Amounts of added DNA and protein can be increased proportionally to the total amount of lipid used. For cationic liposomes, the amount of added DNA can also be increased by employing more cationic lipid. 

DNA and/or protein vaccine entrapment in DRV liposomes is monitored by measuring the vaccine in the suspended pellet and combined supernatants. The most convenient way to monitor DNA entrapment is by using radio-labelled or DNA. For protein entrapment, the use of I-labelled protein tracer is recommended. If a radiolabel is not available or cannot be used, appropriate quantitative techniques should be employed. To determine DNA or protein by such techniques, a sample of the liposome suspension is mixed with Triton X-100 (up to 5% final concentration) or, preferably, with isopropanol (1 1 volume ratio) so as to liberate the entrapped materials. However, if Triton X-100 or the solubilized liposomal lipids interfere with the assay of the materials, liposomal lipids or the DNA must be extracted using appropriate techniques (6). Entrapment values for protein and DNA, whether alone or coentrapped, range between about 20% to 80% (protein) and 30%i to 100%i (DNA) of the initial material depending on the DNA or protein used and, in the case of DNA, the presence or absence of cationic charge. Values are highest for DNA when it is entrapped into cationic DRV (typical values in Table 1). 

Vaccinations Do not give live vaccines concurrently with anakinra. No data are available on the secondary transmission of infections by live vaccines in patients receiving anakinra. Because anakinra interferes with normal immune response mechanisms to new antigens such as vaccines, vaccination may not be effective in... 

Mandates have several justifications. Absent mandates, health plans may have an insufficient incentive to cover vaccines. Such coverage may not be demanded because individuals do not take account of the health and financial externalities in their purchase decisions (Summers 1989). Also, people may underestimate the probability of contracting various diseases (Jensen and Morrisey 1999). Vaccines are more likely to interfere with the spread of the disease than are drug treatments. As the probability of contracting a disease falls, fewer persons maybe expected to demand to be vaccinated for the disease. Also, market power of sellers of vaccines may be lower than for drug treatments. With drugs, persons who may benefit from the treatment are identifiable to sellers, thus allowing firms to extract consumer surplus... 

The second reason for the breakdown of revenue equivalence is that vaccines are more likely to interfere with the spread of a disease than are drug treatments, thus reducing demand for the product. By embedding an economic model within a standard dynamic epidemiological model, they show that the steady-state flow of revenue is greater for drug treatments than for vaccines. 

No formal drug interaction studies of oseltamivir have been performed. Oseltamivir and its carboxylate metabolite do not interact with the cytochrome P450 system. Although probenecid decreases the elimination of oseltamivir, dosage adjustment is not required during coadministration of these drugs because of oseltamivir s margin of safety. Oseltamivir does not interfere with antibody production in response to the influenza vaccine. 

Treatment with immune globulin can interfere with the response to live virus vaccines (e.g., measles,... 

Preventative vaccines are increasingly used during pregnancy, with the intention of protecting the newborn baby from infectious disease, such as influenza, via conferred immunity from the mother (1). To date, no causal relationships have been demonstrated for adverse effects on pregnancy with any approved vaccine. However, potential mechanisms have been suggested by which an induced immune response could interfere with prenatal development. A nonspecific disturbance of the resting balance between the innate and humoral activities of the immune system, for instance, could result in abortion (2). Otherwise, the induced antibodies may have the potential to disturb normal development due to a specific... 

HBIG does not interfere with generation of antibody response to hepatitis B vaccine. Ideally, persons exposed to blood which contains hepatitis B virus should be given combined passive active immunization. 

May interfere with the immune response to live virus vaccines Drug interactions have not been evaluated. However, it is recommended that immunoglobulin be administered separately from other agents... 

Another way to assess ion channel conductance is to use artificial phospholipid vesicles (liposomes) as cell models. These structures (described in more detail in the next chapter) are commonly used to transport vaccines, drugs, enzymes, or other substances to target cells or organs. The vesicles, which are several hundred nanometres in diameter, do not suffer from interference from residual natural ion channel peptides or ionophores, unlike purified natural cells. A liposome model was used to test the ion transport behaviour of the redox-active hydraphile 12.36. The compound transports Na+ and the process can also be monitored using 23Na NMR spectroscopy.26 The presence of the ferrocene-derived group in the central relay allows the ion transport to be redox-controlled - oxidation to ferrocinium completely prevents Na+ transport for electrostatic reasons. Some representative data from a planar bilayer measurement is shown for hydraphile 12.36 in Figure 12.16. 

Live and vector vaccine approaches should take into account the epidemiological situation and health care schemes in the target countries. The efficacy of live vaccines and vectors may be affected by a pre-existing immunity in the population. Live vaccines can also interfere with screening tests, e.g. for salmonellosis in people who handle food or for bovine leukosis in eradication schemes. 

Vaccine excipients (adjuvants and other substances used in the formulation) are treated in the same way as chemical substances. If new substances are introduced, a full safety assessment is required. It may be necessary to assess their toxic potential separately from the vaccine, since the vaccine formulation may interfere with a proper testing. In addition the normal pharmacological and safety tests for vaccines must be performed with the final, formulated product. 

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