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More is not necessarily better: prozone-like effects in passive immunization with IgG.

Despite a century of study, the relationship between Ag-specific Ig concentration and protection remains poorly understood for the majority of pathogens. In certain conditions, administration of high Ab doses before challenge with an infectious agent can be less effective than smaller Ab doses, a phenomenon which is consistent with a prozone-like effect. In this study, the relationship between IgG1, IgG2a, IgG2b, and IgG3 dose, infective inocula, and protection was investigated in a mouse model of Cryptococcus neoformans infection. The activity of each IgG subclass ranged from protective to disease-enhancing depending on both the Ab dose and infective inocula used. Enhanced dissemination to the brain was observed in mice given a high IgG2a dose and a relatively low inoculum. Ab administration had immunomodulatory effects, with cytokine expression in lung, brain, and spleen varying as a function of the infective inoculum Ab dose and IgG subclass. In vitro studies did not predict or explain the mechanism of in vivo prozone-like effects, because all isotypes were opsonic and elicited NO release from macrophages. IgG2a was most efficient in inducing a macrophage oxidative burst. These results reveal that an individual Ab can be protective, nonprotective, or disease-enhancing depending on its concentration relative to a challenge inoculum. Our findings have implications for the potential contribution of Ab responses to defense against microbial diseases because Ab-mediated immunity may be protective, nonprotective, or even deleterious to the host.

Animals↗

Protection of mice from fatal bubonic and pneumonic plague by passive immunization with monoclonal antibodies against the F1 protein of Yersinia pestis.

Monoclonal antibodies (MAbs) to the fraction 1 (F1) protein of Yersinia pestis protected mice against fatal pneumonic as well as bubonic plague from wild-type F1+ organisms. The rare isolation of a virulent F1- isolate from surviving animals supports earlier studies suggesting that improved vaccines should consist of immunogens to protect against F1- variants. The high degree of protection with IgG MAb suggests that secretory IgA is not required for protection from pneumonic plague.

Animals↗

Prevention of hepatitis A through active or passive immunization: Recommendations of the Advisory Committee on Immunization Practices (ACIP).

Routine vaccination of children is the most effective way to reduce hepatitis A incidence nationwide over time. Since licensure of hepatitis A vaccine in 1995, this strategy has been implemented incrementally, starting with the recommendation of the Advisory Committee on Immunization Practices (ACIP) in 1996 to vaccinate children living in communities with the highest rates of infection and disease. These updated recommendations represent the next phase of this hepatitis A immunization strategy. Vaccination of children living in states and communities with consistently elevated rates of hepatitis A will provide protection from disease and is expected to reduce the overall incidence of hepatitis A. This report updates the ACIP's 1996 recommendations on the prevention of hepatitis A through immunization (MMWR 1996;45:[No. RR-151) and includes a) new data about the epidemiology of hepatitis A; b) recent findings about the effectiveness of community-based hepatitis A vaccination programs; and c) recommendations for the routine vaccination of children in states, counties, and communities with rates that are twice the 1987-1997 national average or greater (i.e., > or = 20 cases per 100,000 population) and consideration of routine vaccination of children in states, counties, and communities with rates exceeding the 1987-1997 national average (i.e., > or = 10 but <20 cases per 100,000 population). Unchanged in this report are previous recommendations regarding the vaccination of persons in groups at increased risk for hepatitis A or its adverse consequences and recommendations regarding the use of immune globulin for protection against hepatitis A.

Adult↗