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Addressing Parents' Concerns: Do Multiple Vaccines Overwhelm Or Weaken the Infant's Immune System? Paul A

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Addressing Parents' Concerns: Do Multiple Vaccines Overwhelm Or Weaken the Infant's Immune System? Paul A Addressing Parents’ Concerns: Do Multiple Vaccines Overwhelm or Weaken the Infant’s Immune System? Paul A. Offit, MD*; Jessica Quarles‡; Michael A. Gerber, MD§; Charles J. Hackett, PhDʈ; Edgar K. Marcuse, MD¶; Tobias R. Kollman, MD#; Bruce G. Gellin, MD**; and Sarah Landry‡ ABSTRACT. Recent surveys found that an increasing many as 20 shots by 2 years of age (Table 1). The number of parents are concerned that infants receive too increased number of vaccines given to children and many vaccines. Implicit in this concern is that the infant’s the increased percentage of children receiving vac- immune system is inadequately developed to handle vac- cines have resulted in a dramatic decrease in the cines safely or that multiple vaccines may overwhelm the number of vaccine-preventable diseases. Most young immune system. In this review, we will examine the parents today have never seen many of the diseases following: 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond that vaccines prevent. As a possible consequence of to vaccines; 2) the theoretic capacity of an infant’s im- these trends, recent national surveys found that 23% mune system; 3) data that demonstrate that mild or mod- of parents questioned the number of shots recom- erate illness does not interfere with an infant’s ability to mended for their children,1 and 25% were concerned generate protective immune responses to vaccines; 4) that vaccines might weaken the immune system.1 how infants respond to vaccines given in combination Because most parents receive information and rec- compared with the same vaccines given separately; 5) ommendations about vaccines from their doctors,2 data showing that vaccinated children are not more likely and because these recommendations carry substan- to develop infections with other pathogens than unvac- tial weight with parents,3,4 providers must be knowl- cinated children; and 6) the fact that infants actually edgeable when addressing parents’ concerns. This encounter fewer antigens in vaccines today than they did 40 or 100 years ago. Pediatrics 2002;109:124–129; multiple article will provide health care professionals with vaccines, immunity, parental concerns. information about the effect of vaccines on the in- fant’s immune system and the capacity of the im- mune system to respond safely to multiple vaccines. ABBREVIATIONS. Ig, immunoglobulins; Th, helper T-cell; Hib, Haemophilus influenzae type b; OPV, oral polio vaccine; HIV, hu- man immunodeficiency virus; MMR, measles-mumps-rubella; A BRIEF SUMMARY OF NEONATAL AND INFANT DTP, diphtheria-tetanus-pertussis. IMMUNE RESPONSES The Neonatal Immune System ne hundred years ago, children received 1 Neonates develop the capacity to respond to for- vaccine (the smallpox vaccine). Forty years eign antigens before they are born. B and T cells are Oago, children received 5 vaccines routinely present by 14 weeks’ gestation and express an enor- (diphtheria, pertussis, tetanus, polio, and smallpox mous array of antigen-specific receptors.5 Although vaccines) and as many as 8 shots by 2 years of age. the fetal immune system has the potential to respond Today, children receive 11 vaccines routinely and as to large numbers of foreign antigens, few foreign antigens are present in utero, and cells of the im- mune system are, therefore, primarily “naı¨ve” at From the *Section of Infectious Diseases, Children’s Hospital of Philadel- birth. phia, University of Pennsylvania School of Medicine, and Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania; ‡Division of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; §National Institute of Allergy and Passively Acquired Immunity Infectious Diseases, National Institutes of Health, Bethesda, Maryland; ࿣Di- The neonate is, in part, protected against disease vision of Allergy, Immunology, and Transplantation, National Institute of by maternal immunoglobulins (Ig). Maternal IgG is Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; ¶Section of Infectious Diseases, Children’s Hospital and Re- transported across the placenta before birth and ma- gional Medical Center, University of Washington School of Medicine, Se- ternal secretory IgA is present in breast milk and attle, Washington; #Department of Pediatrics, University of Washington colostrum. These passively acquired antibodies pro- School of Medicine, Department of Epidemiology, University of Washing- vide protection against pathogens to which the ton School of Public Health and Community Medicine, and Children’s mother was immune. However, protection provided Hospital and Regional Medical Center, Seattle, Washington; and **Depart- ment of Preventive Medicine, Vanderbilt Medical College, Nashville, Ten- by passively transferred antibodies is short-lived. nessee. Passively acquired maternal IgG declines during the Received for publication Aug 7, 2001; accepted Oct 4, 2001. first few months of life,6 and most infants are not Reprint requests to (P.A.O.) Children’s Hospital of Philadelphia, Abramson breastfed beyond several months of age.7 More im- Research Building, Room 1202C, 3516 Civic Center Blvd, Philadelphia, PA 19104. E-mail: [email protected] portantly, maternal antibodies offer limited immu- PEDIATRICS (ISSN 0031 4005). Copyright © 2002 by the American Acad- nologic protection when compared with protection emy of Pediatrics. afforded by an infant’s active immune response. 124 PEDIATRICS Vol. 109Downloaded No. 1 January from www.aappublications.org/news 2002 by guest on September 25, 2021 TABLE 1. Number of Vaccines and Possible Number of Injections Over the Past 100 Years Year Number of Possible Number of Possible Number of Vaccines Injections by 2 Years of Age Injections at a Single Visit 1900* 1 1 1 1960† 58 2 1980‡ 75 2 2000§ 11 20 5 * In 1900, children received the smallpox vaccine. † In 1960, children received the smallpox, diphtheria, tetanus, whole-cell pertussis, and polio vaccines. The diphtheria, tetanus, and whole-cell pertussis vaccines were given in combination (DTP), and the polio vaccine (inactivated) was given as a series of 3 injections. ‡ In 1980, children received the DTP, polio, and MMR vaccines. The DTP and MMR vaccines were given in combination and the polio vaccine (live, attenuated) was given by mouth. § In 2000 children received the diphtheria-tetanus-acellular-pertussis, MMR, inactivated polio, Hib, varicella, conjugate pneumococcal, and hepatitis B vaccines. Active Immunity IMMUNE RESPONSE TO VACCINES BY NEONATES Neonates are capable of generating both humoral The neonate is capable of mounting a protective and cellular immune responses to pathogens at the immune response to vaccines within hours of birth.9 time of birth.8,9 Active immunity in the newborn For example, neonates born to mothers with hepatitis includes the full range of B-cell responses including B virus infection mount an excellent protective im- the production of IgM, IgG, and secretory and mo- mune response to hepatitis B vaccine given at birth, nomeric IgA, as well as the development of helper even without additional use of hepatitis B virus- T-cell (Th) and cytotoxic T-cell responses.8,9 In addi- specific immunoglobulin.13–15 In addition, BCG vac- tion, neonates can produce specific Th-cell subsets, cine given at birth induces circulating T-cells that including Th1-type cells that participate in cell-me- protect against bacteremia and subsequent develop- diated immune responses and Th2-type cells that are ment of miliary tuberculosis and tuberculous men- primarily involved in promoting B-cell responses.8,9 ingitis.16–18 The development of active humoral and cellular immune responses in the newborn is necessary to IMMUNE RESPONSE TO VACCINES BY INFANTS meet the tremendous number of environmental chal- The young infant is fully capable of generating lenges encountered from the moment of birth. When protective humoral and cellular immune responses children are born, they emerge from the relatively to multiple vaccines simultaneously. Approximately sterile environment of the uterus into a world teem- 90% of infants develop active protective immune ing with bacteria and other microorganisms. Begin- responses to the primary series of diphtheria-teta- ning with the birth process, the newborn is exposed nus-acellular-pertussis, hepatitis B, pneumococcus, to microbes from the mother’s cervix and birth canal, Hib, and inactivated polio vaccines given between 2 then the surrounding environment. Within a matter months and 6 months of age.19 of hours, the gastrointestinal tract of the newborn, To circumvent the infant’s inability to mount T- initially relatively free of microbes, is heavily colo- cell-independent B-cell responses, polysaccharide 10 nized with bacteria. The most common of these vaccines (Hib and S pneumoniae) are linked to pro- colonizing bacteria include facultative anaerobic bac- teins (ie, diphtheria toxoid, diphtheria toxin mutant teria, such as Escherichia coli and streptococci, and protein, tetanus toxoid, or meningococcal group B strict anaerobic bacteria, such as Bacteroides and Clos- outer-membrane protein) that engage the infant’s 10 tridium. Specific secretory IgA responses directed Th-cells. By converting a T-cell-independent immune against these potentially harmful bacteria are pro- response to a T-cell-dependent response, conjugate duced by the neonate’s intestinal lymphocytes vaccines can be recognized by the infant’s
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