Immunization Safety Review: Multiple Immunizations and Immune Dysfunction (2002)
February 20, 2002
click here for complete report

Scope of Inquiry

Do multiple immunizations have adverse short-term effects on the developing infant immune system that are reflected in increases susceptibility to heterologous infection (infections other than those targeted by the immunization)?

Does exposure to multiple antigens, as administered in vaccines, directly and permanently redirect or skew the immune system toward autoimmunity, as reflected in type 1 diabetes?

Does exposure to multiple antigens, as administered in vaccines, directly and permanently redirect or skew the immune system toward allergy, as reflected in asthma?

Scientific Assessment
Causality Conclusions

The committee concludes that the epidemiological evidence favors rejection of a causal relationship between multiple immunizations and an increase in heterologous infection.

The committee concludes that the epidemiological evidence favors rejection of a causal relation-ship between multiple immunizations and an increased risk of type 1 diabetes.

The committee concludes that the epidemiological evidence is inadequate to accept or reject a causal relationship between multiple immunizations and increased risk of allergic disease, particularly asthma.

 Biological Mechanisms Conclusions
Autoimmune Disease

In the absence of experimental or human evidence regarding molecular mimicry or mercury-induced modification of any vaccine component to create an antigenic epitope capable of cross-reaction with self epitopes as a mechanism by which multiple immunizations under the U.S. infant immunization schedule could possibly influence an individual's risk of autoimmunity, the committee concludes that these mechanisms are only theoretical.

The committee concludes that there is weak evidence for bystander activation, alone or in concert with molecular mimicry, as a mechanism by which multiple immunizations under the U.S. infant immunization schedule could possibly influence an individual's risk of autoimmunity.

In the absence of experimental or human evidence regarding loss of protection against a homologous infection as a mechanism by which multiple immunizations under the U.S. infant immunization schedule could possibly influence an individual's risk of autoimmunity, the committee concludes that this mechanism is only theoretical.

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 autoimmunity, the committee concludes that this mechanism is only theoretical.

Considering molecular mimicry, bystander activation, and impaired immunoregulation collectively rather than individually, the committee concludes that there is weak evidence for these mechanisms as means by which multiple immunizations under the U.S. infant immunization schedule could possibly influence an individual's risk of autoimmunity. 

Allergic Disease

The committee concludes that there is weak evidence for bystander activation as a mechanism by which multiple immunizations under the U.S. infant immunization schedule could possibly influence an individual's risk of allergy.

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. 

Heterologous Infection

The committee concludes that there is strong evidence for the existence of biological mechanisms by which multiple immunizations under the U.S. infant immunization schedule could possibly influence an individual's risk for heterologous infections.

Significance Assessment
Conclusions

The committee concludes that concern about multiple immunizations has been, and could continue to be, of societal significance in terms of parental worries, potential health burdens, and future challenges for immunization policy-making.

Public Health Response Recommendations
Policy Review

The committee recommends that state and federal vaccine policymakers consider a broader and more explicit strategy for developing recommendations for the use of vaccines.

The committee does not recommend a policy review - by the CDC's Advisory Committee on Immunization Practices (ACIP), the American Academy of Pediatrics' Committee on Infectious Diseases, and the American Academy of Family Physicians - of the current recommended childhood immunization schedule on the basis of concerns about immune system dysfunction.

The committee does not recommend a policy review by the Food and Drug Administration's Vaccines and Related Biologic Products Advisory Committee of any currently licensed vaccines on the basis of concerns about immune system dysfunction.

Research
Epidemiological Research

The committee recommends exploring the feasibility of using existing vaccine surveillance systems, alone or in combination, to study safety questions related to asthma and other important allergic disorders, as well as to type I diabetes and other important autoimmune diseases.

The committee recommends exploring the use of cohorts for research on possible vaccine-related disease risks. Furthermore, the committee recommends that disease registries and research programs for autoimmune and allergic disorders routinely collect immunization histories as part of their study protocol.

 Basic Science and Clinical Research

The committee recommends continued research on the development of the human infant immune system.

The committee endorses current research efforts aimed at identifying genetic variability in human immune system development and immune system responsiveness as a way to gain a better understanding of genetic susceptibility to vaccine-based adverse events.

The committee recommends exploring the feasibility of collecting data on surrogate markers for autoimmune and allergic disorders in the vaccine testing and licensing process.

The committee recommends exploring surrogates for allergy and autoimmunity in existing cohort studies of variations in the vaccine schedule.

Communication

The committee recommends that an appropriate panel of multidisciplinary experts be convened by the Department of Health and Human Services. It would develop a comprehensive research strategy for knowledge leading to the optimal design and evaluation of vaccine risk-benefit communication approaches.

updated 06.19.06