The hygiene hypothesis is a theoretical model, originally proposed on the basis of epidemiological data. The biological mechanisms by which this model could explain an increase in incidence of allergic diseases are substantial, and the model is considered to be moderately to strongly plausible. However, the potential contribution of vaccine-preventable diseases as part of this theory is minimal. In the absence of experimental or human evidence regarding mechanisms related to the hygiene hypothesis as a means by which multiple immunizations under the U.S. infant immunization schedule could possibly influence an individual’s risk of allergy, the committee concludes that this mechanism is only theoretical.

The committee concludes that there is weak evidence for the existence of any biological mechanisms, collectively or individually, by which multiple immunizations under the U.S. infant immunization schedule could possibly influence an individual’s risk of allergy.

Multiple Immunizations and Heterologous Infections

Simultaneous or sequential infection or immunization with multiple vaccines or antigens can, through various mechanisms, influence the magnitude and/or quality of the immune response to individual antigens, either impeding or enhancing the immune response to one or the other, thereby affecting immune-mediated resolution of an infection and/or the development of protective immunity. There are several potential mechanisms by which this can occur, which vary with the nature of the antigen/agent and with the component of the immune response being evaluated or most important for providing protection. These include immune interference, T cell cross-reactivity, carrier-induced epitope suppression, and competition for antigen presentation (peptide competition for binding to MHC molecules or competition between T cells for the same antigen presenting cells). These mechanisms have been discussed in earlier reports from this committee (IOM, 2001a), and some have also been referred to in the preceding sections of this report. There is experimental animal evidence for each of these mechanisms in certain contexts. For the latter two mechanisms, there is also evidence from human studies that are relevant to the possible effects of multiple immunizations on risk for heterologous infections, which is briefly reviewed here.

Carrier-Induced Epitope Suppression

This process was first described in model systems, but has become clinically important in the context of conjugate vaccines. In such systems, the carrier is a protein antigen, to which is conjugated (covalently linked to create a single molecule) a non-protein antigen. In clinical practice, conjugation of a bacterial non-protein antigen to a protein carrier has been used to convert a



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