Immunization: passive

The use of monoclonal antibodies as therapeutics has become commonplace. Antibodies or chimeric proteins against TNF-a are very effective in quelUng certain inflammatory diseases. Trastuzumab (against HER2) is effective in reversing the growth of some breast tumors. As of 2005, there were 15 antibody therapeutics approved for use in the US. 

Several groups have found that some individuals have titers of antibodies against the A6 peptide. Unfortunately, consensus regarding a relationship to Alzheimer s disease has not yet emerged as there are reports of increased titers with disease (Nath et al., 2(X)3), decreased titers with disease (Weksler et al., 2002) or no effect of disease (Hyman et al., 2001). It should be noted that the antibody titers observed are extremely low compared to those observed after immuiuzation. Moreover, it is not clear the degree to which endogenous A6 may interfere with the detection of anti-A6 antibodies by ELISA (see Li et al., 2004). 

this has led to a short, open label trial of human intravenous immunoglobulin, an FDA approved product that has benefit in several types of disorders, including multiple sclerosis. Dodel et al. (2004) reported that 

Acknowledgments. Drs. Morgan and Gordon receive support from the foUowing Awards ROl AG15490, ROl AG 18478, ROl NS48335, ROl AG 25509, P50 AG25701 

What are the two main neuropathological hallmarks of Alzheimer s disease  

What ai e the two main neuropathological haUmarks of Alzhehner s disease  

Marcel Dekker, Inc. 270 Madison Avenue, New York, New York 10016 

STRATEGIES FOR IMPLEMENTING PNEUMOCOCCAL AND INFLUENZA VACCINE RECOMMENDATIONS 

Barriers to achieving high pneumococcal and infiuenza vaccination levels among adults include (1) missed opportunities to vaccinate adults during contacts with health care providers in offices, outpatient clinics, and hospitals (2) lack of vaccine delivery systems in the public and private sectors that can 

In practice-based tracking systems, providers identity patients who are at risk and maintain rosters showing the proportion who receive vaccination. Physicians using such a tracking system have administered 30% more influenza vaccine than those not using the system (116). 

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Human immunoglobulin preparations from pools of a great number of people (>1,000) with assumed antibodies against common viruses are used as a means of passive immunization in acute infections. More specific antibody preparations with high titers from patients who recovered recently from a viral disease or were immunized against toxins are also available in... 

Active and passive immunity involve tiie use of agents that stimulate antibody formation (active immunity) or tiie injection of ready-made antibodies found in tiie serum of immune individuals or animals (passive immunity). The following sections describe active and passive immunity. 

Passive immunity is obtained from the administration of immune globulins or antivenins. This type of immunity provides die individual with ready-made antibodies from another human or an animal (see Pig. 54-1). Passive immunity provides immediate immunity to die invading antigen, but lasts for only a short time. The Summary Drug Table Agents for Fhssive Immunity identifies agents for passive immunizations. Display 54-4 provides an example of passive immunity. 

Passive immunization of exposed, susceptible individuals who are at greater risk of complications from varicella than are healthy individuals... 

An example of passive immunity is the administration of immune globulins (see Summary Drug Table Agents for Passive Immunity), such as hepatitis B immune globulin. Administration of this vaccine is an attempt to prevent hepatitis B after the individual has been exposed to the virus. 

Immunosera and human immunoglobulins depend for their protective effects on their content of antibodies derived, in the case of immunosera, flxm immunized animals and, in the case of immunoglobulins, flxm humans who have been immunized or who have high antibody titres consequent upon prior infection. This form of immunity, known as passive immunity, is achieved immediately but is limited in its duration to the time that protective levels of antibodies remain in the circulation see also Chapter 16. 

Immune globulin (IG) is a solution containing antibodies from sterilized pooled human plasma that provides passive immunization against various infectious diseases, including hepatitis A.5 Immune globulin is available for either intravenous (IVIG)... 

Centers for Disease Control and Prevention. Prevention of hepatitis A thorough active or passive immunization recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2006 55(RR-07) l-30. 

B23. Beutler, B., Milsark, I. W., and Cerami, A., Passive immunization against cachectin/tumor necrosis factor protects mice from the lethal effects of endotoxin. Science 229,869-871 (1985)... 

In passively immunized neonatal rats, Tyv-specific antibodies exclude larvae from the epithelium (Appleton et al., 1988), where large numbers of excluded larvae become entrapped in mucus (Carlisle et al., 1991a). Similarly, when immune adult rats are challenged with larvae, many luminal parasites are observed entrapped in mucus (Lee and Ogilvie, 1982 Bell et al, 1984). Larvae are neither injured nor killed by mucus entrapment, which is reversible and is not a requirement for expulsion (Carlisle et al., 1990). Rather, mucus appears to participate in expulsion by temporarily confining larvae to the lumen, thus facilitating their elimination from the intestine by normal physiological processes. 

In contrast to the protection afforded to suckling rats by Tyv-specific antibodies, passive immunization of weaned rats fails to cause expulsion of T. spiralis (Otubu et al., 1993). Nevertheless, Tyv-specific antibodies do affect the behaviour of larvae in the intestines of weaned rats in the early hours following infection in that larvae are immobile in the intestinal tissue of such rats, though immobility is reversed when the larvae moult. These findings provide further evidence that antibodies specific for Tyv interfere with the LI larva s niche. 

Simple passive immunization with Tyv-specific antibodies does not protect adult rats against T. spiralis, however, it has been shown that prior infection with an unrelated intestinal nematode (Heligmosomoides polygyrus) in combination with passive immunization with Tyv-specific antibodies promotes expulsion of T. spiralis larvae (Bell et al, 1992). The way(s) that II. polygyrus infection synergizes with antibodies is not known. 

In summary, the in vivo protective effects of Tyv-specific antibodies, exclusion and immobility, can now be effectively studied using an in vitro model of the intestinal epithelium. Larvae are prevented from entering epithelial cells by caps of immune complexes or by binding of antibody to Tyv in the absence of immune complex formation. These effects would correlate with exclusion of larvae from epitheha observed in passively immunized rats. Larvae are encumbered as they migrate within epithelial monolayers, an effect that may correlate with immobility of larvae observed in vivo. It is reasonable to conclude that in the animal host the different effects work in combination, most iikeiy in cooperation with innate host defences, to cause nematode expuision from the intestine. 

Enterotoxigenic E. coli B subunits of the heat labile toxin (LTB) Tomato fruit and leaf Offspring were passively immunized through oral immunization of parents. 91... 

Enterotoxigenic E. coli epitope and rotavirus epitope fused to CTB Potato tuber Mice developed detectable levels of serum and intestinal antibodies. Immunogenic in mice against ETEC, rotavirus, and V. cholerae when delivered orally. Symptoms reduced in passively immunized mouse neonates following rotavirus challenge. 63... 

Thus, the tetravalency, anti-inflammatory properties and molecular stability of slgA make it particularly suitable for protective passive immunity when applied to mucosal surfaces. To date, the clinical evaluation of slgA protection in humans and animal models has been very limited. Indeed most studies have employed monomeric IgA monoclonal antibodies [3,15]. Hence, differences in IgA and IgG protective activities at the mucosal level have often not been observed [15]. Only a few studies have demonstrated the superior activity of polymeric IgA or slgA compared with monomeric IgG or IgA [16]. In order to determine the efficacy of slgA, future animal experiments and clinical trials are needed to compare the activities of IgG monoclonal antibodies and their slgA counterparts. The ability to engineer slgAs in plants will allow these comparisons to be made [17]. 

Zearalenone (mycotoxin) scFv Passive immunization of animals in their feed A. thaliana (ecotype Columbia) Inducible lac No targeting signal - 58... 

Antibodies Passive immunization against various diseases... 

Polyclonal antibody preparations have been used to induce passive immunity against a range of foreign (harmful) agents, and vaccines are used efficiently, and safely, to promote active immunization. Adjuvants are usually co-administered with the vaccine preparation, in order to enhance the immune response against the vaccine. 

Polyclonal antibody preparations have been used for several decades to induce passive immunization against infectious diseases and other harmful agents, particularly toxins. The antibody preparations are usually administered by direct i.v. injection. While this affords immediate immunological protection, its effect is transitory, usually persisting for only 2-3 weeks (i.e. until the antibodies are excreted). Passive immunization can be used prophylactically (i.e. to prevent a future medical episode) or therapeutically (i.e. to treat a medical condition that is already established). An example of the former would be prior administration of a specific anti-snake toxin antibody preparation to an individual before they travel to a world region in which these snakes are commonly found. An example of the latter would be administration of the anti-venom antibody immediately after the individual has experienced a snake bite. 

Antibody preparations used to induce passive immunity may be obtained from either animal or human sources. Preparations of animal origin are generally termed antisera , and those sourced from humans are called immunoglobulin preparations . In both cases, the predominant antibody type present is IgG. 

Although specific antisera have proven invaluable in the treatment of a variety of medical conditions (Table 13.1), they can also induce unwanted side effects. Particularly noteworthy is their ability to induce hypersensitivity reactions some such sensitivity reactions (e.g. serum sickness ) are often not acute, whereas others (e.g. anaphylaxis) can be life threatening. Because of such risks, antibody preparations derived from human donors (i.e. immunoglobulins) are usually preferred as passive immunizing agents. 

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