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Acellular Pertussis Vaccines

Pertussis toxin (PT), also termed lymphocytosis-promoting factor, induces many of the biologic activities of the organism: histamine sensitization, lymphocytosis-promoting activity, pancreatic islet cell activation, and immune response enhancement. PT is composed of several subunits and has a structure similar to other bacterial toxins such as diphtheria. When administered to mice, PT induces antibodies that protect against lethal respiratory and intracerebral challenge with live B pertussis organisms. Many investigators believe PT has a central role in providing clinical protection for humans. For incorporation into a vaccine, active toxin must be inactivated (or toxoided) either chemically or genetically pertussis, seizures, brain damage.

Filamentous hemagglutinin (FHA), a component of the cell wall, is believed to be crucial for the attachment of organisms to the respiratory epithelium. Mice immunized with FHA are protected against lethal respiratory challenge with pertussis but not against intracerebral challenge.

Agglutinogens are fimbrialassociated surface components that stimulate production of agglutinating antibodies. Although pertussis carries several different agglutinogens, three types (1, 2, and 3) occur in various combinations in the majority of strains. Recent data suggest that agglutinogens 2

Even with significantly fewer adverse reactions, the efficacy of the acellular preparations needed to be demonstrated before allowing

TABLE 2 -- Adverse Reactions to Pertussis Vaccines

*Unable to determine from reports.

general, most of the acellular vaccines were highly effective.

With these interesting and complex data available, how do regulating bodies and vaccine advisory groups decide which vaccines to license and which ones to recommend? It is likely that multiple acellular vaccines will be licensed by the United States Food and Drug Administration if they can be proven safe, be consistent from lot to lot, and have adequate efficacy rates. It could be argued that any of the acellular products is significantly more effective than the one licensed whole-cell vaccine studied in the NIH-funded trials in Italy and Sweden and should be approved as soon as possible. The more difficult question is whether the advisory bodies will recommend one vaccine over another based on the results of efficacy trials. Factors such as cost are also of concern; multiple-component vaccines probably will be more expensive than single or bivalent vaccines. Countries that have more limited resources may choose to purchase a less reactogenic acellular product that contains fewer antigens, exchanging a lower cost for a less effective product. It is time to license acellular pertussis vaccines for routine use in infants.

Comment:

The two absolute contraindications to further pertussis vaccination are an immediate anaphylactic reaction and the onset of encephalopathy within 7 days. A prior serious reaction (a convulsion within 3 days, inconsolable crying lasting more than 3 hours, a fever of 40.5E°C [105E°F] or higher, or a hypotonic-hyporesponsive episode) is considered a precaution against further vaccination that may be outweighed, for example, by a local outbreak of pertussis judged to pose a greater threat to the child.

What to do about pertussis immunization for children who have neurologic disorders remains a complicated decision. In general, a child who has progressive central nervous system disease should have pertussis vaccine deferred, whereas a child who has a stable disorder such as cerebral palsy should be immunized according to the usual schedule. Children who have well-controlled seizures can be immunized, but a child who has had recent or poorly controlled seizures usually should have vaccination postponed. A family history of seizures or of sudden infant death syndrome should not delay pertussis immunization; neither should a low-grade fever.

The standard schedule for pertussis vaccine includes five doses: a primary series at 2, 4, 6, and 15 to 18 months of age, followed by a reinforcing dose prior to school entry (4 to 6 y).