Cell Pertussis Vaccine Research Articles

Pertussis immunization for adolescents: What are we waiting for?

Immunization against pertussis (whooping cough) has been part of the routine childhood immunization program for over 50 years. Until 1997, a whole cell pertussis vaccine was used, most often combined with diphtheria and tetanus toxoids; in some jurisdictions it was combined with inactivated poliovirus vaccine and later with Haemophilus influenzae type b (Hib)-conjugate vaccine. Vaccine doses were given at two, four, six and 18 months of age, and again at four to six years of age. Use of the whole cell vaccine in children seven years of age and older was not recommended because “the incidence and severity of the disease greatly decrease with age, and because adverse reactions are (may be) more common in older children and adults...” (1–3). Over a one-year period in 1997/98, all provinces in Canada began using an acellular pertussis vaccine, again combined with diphtheria and tetanus toxoids, inactivated poliovirus vaccine and Hibconjugate vaccine. In 1999, an acellular pertussis vaccine that was combined with tetanus and diphtheria toxoids (TdaP) (Adacel, Aventis Pasteur, Canada) was licensed for use in individuals 12 to 54 years of age in Canada. In Germany, a similar adolescent and adult TdaP was licensed in 2000 (Boostrix, SmithKline Beecham, Belgium). With the availability of a TdaP product in Canada, should routine universal immunization against pertussis be provided for all adolescents and adults? Some of the key issues to be considered when answering this question are addressed in the questions and answers that follow. The focus of the present paper is on the adolescent population; however, similar issues about adult immunization need to be addressed by internal medicine and family practice practitioners.

Fifth vaccination with dipthteria, tetanus and acellular pertussis is beneficial in four- to six-year-olds.

Diphtheria, tetanus and pertussis serum antibody titers were assessed before a fifth dose of diphtheria-tetanus-acellular pertussis (DTaP) or diphtheria-tetanus-whole cell pertussis (DTwP) vaccination at age 4 to 6 years. Healthy children who had participated in a series of National Institutes of Health-sponsored trials assessing DTwP and DTaP vaccines provided prevaccination sera before a fifth dose of DTwP or DTaP. The trial design was prospective, randomized and double blind. Diphtheria, tetanus and pertussis antibody titers were measured by enzyme-linked immunosorbent assay. Pertussis results are expressed in enzyme-linked immunosorbent assay units/ml based on US Food and Drug Administration reference sera. Tetanus and diphtheria toxin concentrations are expressed in IU/ml with a WHO international reference sera as a standard. For diphtheria 100% of the children had antibody titers above the minimum protective level of 0.01 IU/ml and 86 to 100% (depending on prior vaccine product) had titers >0.1 IU/ml. However, only 0 to 40% of the children had antibody titers > or =1.0 IU/ml, a titer associated with more certain durable protection. For tetanus none of the children had an antibody titer below 0.01 IU/ml, and 93 to 100% had titers > or =0.1 IU/ml, a titer associated with more certain, durable protection. For pertussis the geometric mean concentrations of antibody before booster were uniformly very low, and the percentage of children exceeding the minimum detectable titer of antibody by 4-fold was also low. Before a 4- to 6-year-old booster, a large proportion of children have titers of antibody to diphtheria below the certain, durable protective level. Because serologic correlates and minimum protective titers of antibody to pertussis antigens have not been established, the relevance of the low titers determined in the current study is unknown but a potential concern.

The efficacy of whole cell pertussis immunisation: collected data on a vaccine produced in France

The place of whole cell pertussis vaccines in paediatric immunisation schedules is under re-evaluation by public health authorities in many countries, with the expectation that the newly licensed acellular Bordetella pertussis vaccines will induce fewer adverse events while providing equivalent efficacy. In France, for instance, the CSHPF (Conseil supérieur d'hygiène public de France) recently modified its long-standing recommendation that French children only receive whole cell pertussis vaccine. Consequently, an acellular pertussis vaccine may be used for the first booster, at 16–18 months of age, and should be used for the reinforcing dose at 11–13 y of age. French children, nonetheless, continue to receive whole cell pertussis vaccine for the primary series immunisations at 2, 3, and 4 months, as the only whole cell pertussis vaccine available in France (licensed by Aventis Pasteur) has a long-established record of safety and protective efficacy. A review of its unpublished and published clinical results, obtained from studies throughout the world, demonstrates an efficacy of from 84–100% in six different retrospective analyses or outbreak investigations and a protective efficacy of 92% by clinical trial. Public Health (2001) 115, 119–129.

The efficacy of whole cell pertussis immunisation collected data on a vaccine produced in France

The place of whole cell pertussis vaccines in paediatric immunisation schedules is under re-evaluation by public health authorities in many countries, with the expectation that the newly licensed acellular Bordetella pertussis vaccines will induce fewer adverse events while providing equivalent efficacy. In France, for instance, the CSHPF (Conseil supérieur d'hygiène public de France) recently modified its long-standing recommendation that French children only receive whole cell pertussis vaccine. Consequently, an acellular pertussis vaccine may be used for the first booster, at 16–18 months of age, and should be used for the reinforcing dose at 11–13 y of age. French children, nonetheless, continue to receive whole cell pertussis vaccine for the primary series immunisations at 2, 3, and 4 months, as the only whole cell pertussis vaccine available in France (licensed by Aventis Pasteur) has a long-established record of safety and protective efficacy. A review of its unpublished and published clinical results, obtained from studies throughout the world, demonstrates an efficacy of from 84–100% in six different retrospective analyses or outbreak investigations and a protective efficacy of 92% by clinical trial. Public Health (2001) 115 , 119–129.

Pertussis immunization for adolescents: What are we waiting for?

Immunization against pertussis (whooping cough) has been part of the routine childhood immunization program for over 50 years. Until 1997, a whole cell pertussis vaccine was used, most often combined with diphtheria and tetanus toxoids; in some jurisdictions it was combined with inactivated poliovirus vaccine and later withHaemophilus influenzaetype b (Hib)-conjugate vaccine. Vaccine doses were given at two, four, six and 18 months of age, and again at four to six years of age. Use of the whole cell vaccine in children seven years of age and older was not recommended because "the incidence and severity of the disease greatly decrease with age, and because adverse reactions are (may be) more common in older children and adults..." (1-3). Over a one-year period in 1997/98, all provinces in Canada began using an acellular pertussis vaccine, again combined with diphtheria and tetanus toxoids, inactivated poliovirus vaccine and Hib-conjugate vaccine. In 1999, an acellular pertussis vaccine that was combined with tetanus and diphtheria toxoids (TdaP) (Adacel, Aventis Pasteur, Canada) was licensed for use in individuals 12 to 54 years of age in Canada. In Germany, a similar adolescent and adult TdaP was licensed in 2000 (Boostrix, SmithKline Beecham, Belgium). With the availability of a TdaP product in Canada, should routine universal immunization against pertussis be provided for all adolescents and adults? Some of the key issues to be considered when answering this question are addressed in the questions and answers that follow. The focus of the present paper is on the adolescent population; however, similar issues about adult immunization need to be addressed by internal medicine and family practice practitioners.

Reactogenicity and Safety of DTPa Vaccine and Haemophilus influenzae Type b Conjugate Vaccine (Hib) in a Single Injection vs DTPw and Hib as Separate Injections as a Booster Vaccination in 18-Month-Old Children

Objective To compare the reactogenicity and safety of the administration of diphtheria-tetanus-acellular pertussis (DTPa) and Haemophilus influenzae type b conjugate (Hib) vaccines in one injection with those of the simultaneous administration of diphtheria-tetanus-whole cell pertussis (DTPw) and Hib vaccines in opposite limbs as booster doses to 18-month-old children previously primed with three doses of DTPw and Hib vaccines as a primary vaccination course.

Investigation of an Aerosol Challenge Model as Alternative to the Intracerebral Mouse Protection Test for Potency Assay of Whole Cell Pertussis Vaccines

The current potency test for whole cell pertussis vaccines, the intracerebral mouse protection test, is still the only assay which has shown a correlation with protection in children. However, it has considerable disadvantages as it uses a severe challenge procedure and the results tend to show significant intra- and inter-laboratory variation. An alternative assay based on non-lethal aerosol challenge of mice has been investigated as a replacement for the current intracerebral mouse protection test. Evaluation of this indicated that the aerosol system allowed consistent inoculation of bacteria into mice and gave good reproducibility. The protective capacity of different vaccine preparations was distinguished by this assay. Furthermore, the viable counts of Bordetella pertussis in the lungs of challenged mice were immunisation dose-dependent, which allowed the relative potency of vaccines to be calculated. Comparison of potency of five batches of vaccine from different manufacturers assayed by both the intracerebral and the aerosol challenge methods ranked the vaccines in identical order. The results suggest that this method has potential for use as a potency test for whole cell pertussis vaccine which would result in a great reduction in the number of animals used. It would also replace the lethal challenge by a non-lethal procedure and thereby avoid the use of the severe intracerebral challenge procedure.

Investigation of cellular and humoral immune responses to whole cell and acellular pertussis vaccines

New generation acellular pertussis vaccines were compared with the established whole cell pertussis vaccine for the induction of humoral and cellular immune-responses in mice. At the same time, the in vivo protective effect of these two types of vaccine was also compared in both intracerebral (ic) and aerosol challenge models. In general, whole cell vaccine induced lower antibody titres to pertussis toxin, filamentous haemagglutinin and pertactin than the acellular vaccine. Nitric oxide concentration in macrophage cultures was used as a marker for macrophage activation. The nitric oxide concentrations in the macrophage cultures from mice following immunisation with the whole cell vaccine were higher than those from mice immunised with the acellular vaccine, which indicated that the whole cell vaccine was more effective than the acellular vaccine in activating macrophages. This was associated with better protection in vivo after challenge. After ic challenge of mice following immunisation with whole cell or acellular vaccine, 90% of the whole cell vaccine group survived compared with 40% of the acellular vaccine group at the vaccine dose selected. Following aerosol challenge, mice in the whole cell vaccine group showed faster clearance of bacteria from the lungs than those in the acellular vaccine group. Our findings suggest that the different types of pertussis vaccines may achieve protection in different ways and that CMI may play an important role in eliminating bacteria which escape humoral defence mechanisms.

Interleukin-1β-dependent changes in the hippocampus following parenteral immunization with a whole cell pertussis vaccine

Neurological side effects are a major cause of concern following immunization with a number of vaccines, especially the whole cell pertussis vaccine (Pw). In this study we report that IL-1β concentrations were significantly increased in the hippocampus following subcutaneous (s.c.) injection of Pw, and that this was accompanied by increased activity of the stress-activated kinase, c-Jun-N-terminal kinase (JNK) and a decrease in glutamate release. These effects were mimicked by s.c injection of active pertussis toxin (PT) or lipopolysaccharide (LPS). Incubation of hippocampal synaptosomes in the presence of Pw, PT or LPS also resulted in increased JNK activation and decreased glutamate release, effects which were mimicked by IL-1β and blocked by the IL-1 receptor antagonist (IL-ra). Our observations are consistent with the hypothesis that IL-1β induced by active bacterial toxins present in vaccine preparations, mediate the neurochemical and perhaps the neurological effects of Pw.

Can immunization affect the development of allergy?

A changing pattern of infections may be of importance for the increase in prevalence of asthma and other allergic diseases in developed countries during recent decades. The clear inverse relation between number of siblings and atopy observed in several studies may be related to a protective role of infections, although specific information is inconclusive. A recent study showed that positive tuberculin responses in schoolchildren correlated with a lower prevalence of atopic disorders, but other studies did not find a relation between BCG vaccination and allergic disease or sensitization. Transient production of IgE antibodies to pertussis toxin has been demonstrated after pertussis immunization; however, randomized clinical trials involving both whole cell and acellular pertussis vaccines have failed to show any enhancement of atopic manifestations in children. Epidemiologic investigations indicate that viral infections may either promote (RSV) or inhibit (hepatitis A, measles) atopy, although data are scarce. In conclusion, the evidence is limited regarding a direct role of vaccinations for development of atopic manifestations, but speaks against a major effect of some types of vaccinations. On the other hand, since some infections may offer protection in relation to allergy, vaccination could result in an increased risk.

Tolérance du vaccin anticoquelucheux acellulaire lors du rappel de la deuxième année de vie

Severe reactions to whole cell pertussis vaccine are the main reason for the poor adhesion of parents and practitioners to pertussis vaccine booster injections in children, leading to a poor immunization in the population, particularly in young adults. The acellular pertussis vaccine appears to be better tolerated while keeping a good immunogenicity. In a randomized multicentric study on pertussis vaccine booster injection tolerance in 386 15-20 month-old children, we confirmed the better local and general tolerance of the acellular vaccine as compared with the whole cell vaccine. This should help to develop a positive opinion toward pertussis vaccine among parents and practitioners, and to improve the level of active pertussis immunization among children, adolescents, and young adults.

Effect of pertussis toxin on the induction of nitric oxide synthesis in murine macrophages and on protection in vivo

Macrophages from mice immunised with whole cell pertussis vaccine (WCV) responded in vitro to selected antigens by nitric oxide (NO) synthesis. This process was closely associated with macrophage activation. Because of the postulated role of traces of pertussis toxin (PT) in the protective effects of WCV, native PT and a genetically detoxified PT (g-PT) in combination with either a heat-treated whole cell pertussis vaccine (dWCV) or a three component acellular vaccine (ACV), were examined for their effects on NO induction in murine macrophages. The protective effects of these two forms of PT were examined in parallel using the intracerebral (ic) and aerosol challenge routes. Cultures of macrophages from mice immunised with dWCV and ACV, PT or g-PT produced less NO than comparable cultures from mice vaccinated with WCV. However, vaccination with either dWCV or ACV in combination with PT but not with g-PT, induced a significant increase (126–157%) in NO production by cultured cells and was associated with increased protection against challenge by both the ic and aerosol routes. These data indicate that a low concentration of PT acting as a co-factor in combination with other Bordetella pertussis antigens, can potentiate the activation of macrophages and that this process plays a key role in protection against infection.

Pertussis immunisation in Europe - the situation in late 1999.

The history of pertussis in European countries has clearly shown that immunisation decreases the morbidity associated with the disease. Inactivated whole cell pertussis vaccines (wP) have been used in some national vaccination programmes for over 30 years

Extensive swelling after booster doses of acellular pertussis-tetanus-diphtheria vaccines.

Diphtheria and tetanus toxoid combined with acellular pertussis (DTaP) vaccines are less reactogenic than diphtheria and tetanus toxoid combined with whole cell pertussis (DTwP) vaccines. However, local reactions increase in rate and severity with each successive DTaP dose, and swelling of the entire injected limb has been reported after booster doses. We reviewed reports of swelling of the entire thigh or upper arm after the fourth and fifth dose, respectively, of DTaP vaccines administered in the National Institutes of Health multicenter comparative DTaP studies. Relationships were explored among reports of severe swelling, rates of other reactions, quantity of vaccine contents, and prevaccination and postvaccination antibody levels to pertussis toxin, tetanus toxin, and diphtheria toxin. Entire thigh swelling was an unsolicited reaction reported in 20 (2%) of the 1015 children who received 4 consecutive doses of the same DTaP vaccine. The reaction was associated with 9 of the 12 DTaP vaccines evaluated. Although there were no reports of swelling of the entire upper arm in 121 children given a fifth dose of the same DTaP, 4 (2.7%) of 146 recipients of 5 doses of a mixed schedule of DTaP vaccines experienced such swelling. Rates of other reactions were higher in children with entire thigh swelling than in those without. Of the children with entire thigh swelling, 60% had local pain, and 60% had erythema. All swelling subsided spontaneously without sequelae. There was a significant linear association between the rates of entire thigh swelling after dose 4 and diphtheria toxoid content in the DTaP products. Lesser degrees of swelling (>50 mm but less than entire limb) correlated with pertussis toxoid content after dose 4 and aluminum content after dose 5. No relationship was established between levels of serum antibody to diphtheria, tetanus, or pertussis toxin and rates of swelling of the whole thigh. Booster doses of DTaP vaccines can cause entire limb swelling, which is usually associated with redness and pain. Our data suggest that this extensive swelling reaction may be more common with vaccines containing high diphtheria toxoid content.

Experience with diphtheria toxoid-tetanus toxoid-acellular pertussis vaccine in Japan.

In Japan, the morbidity rate for pertussis per 100,000 population was 147.6 in 1950 when whole cell pertussis vaccine was introduced but dropped to 0.2 in 1972 when routine immunization with a combined vaccine consisting of diphtheria toxoid, tetanus toxoid, and whole cell pertussis had been widely accepted. Thereafter, adverse reactions to the whole cell pertussis vaccine became a social problem and lowered the acceptance of the vaccine. As a result, the morbidity rate increased to 11.3 in 1979. Introduction of the safer yet efficacious acellular pertussis vaccine, consisting of mainly pertussis toxoid and filamentous hemagglutinin, into the routine childhood vaccination in combination with diphtheria and tetanus toxoids in 1981 increased the acceptance rate. The lowest morbidity rate, 0.1, was achieved in 1993. During the next 16 years, almost all cases were in unvaccinated or incompletely vaccinated persons. Regardless of whether whole cell or acellular pertussis vaccine was used, > 90% of the reported pertussis cases were in children < 10 years of age until 1990. However, since 1991, the rate of pertussis in young adults 20-44 years of age has been clearly increasing. To control pertussis, booster vaccination with diphtheria toxoid-tetanus toxoid-acellular pertussis vaccine in adults should be considered.

Cellular and acellular pertussis vaccines in adults.

Immunization against pertussis after childhood previously was considered unnecessary, because severe illness and complications rarely developed in older persons. The rising incidence of pertussis among older adolescents and adults and the transmission of infection from adults to infants suggest that booster immunization may be necessary to more effectively control pertussis in all age groups. Whole cell pertussis vaccines are regarded as unsuitable for routine use in adults because of reports of frequent moderate to severe reactogenicity at the injection site and occasional systemic reactions. The introduction of safe and effective acellular pertussis vaccines provides us with an opportunity to reconsider booster immunization of adolescents and adults. Several vaccines containing purified component(s) of Bordetella pertussis have been well tolerated and highly immunogenic when given to healthy adults. A clear understanding of the impact of pertussis in adolescents and adults will help to define the need for booster immunization after childhood.

Standardization of Acellular Pertussis Vaccines

In comparison with the current whole cell pertussis vaccine, the new generation of acellular pertussis vaccines opens new opportunities to improve the standardization of the product, because well defined and characterized components are used in these new products.However, different compositions, purification and inactivation methods are used by different manufacturers. Consequently the various acellular pertussis vaccines in the world are difficult to compare in a meaningful manner using simple laboratory tests. In addition, the absence of a reliable animal model and serological correlates with protection in children are other complicating factors.For that reason it seems that the consistency in manufacturing based on a clinically validated production process is the best way to ensure the safety and efficacy of routinely produced acellular pertussis vaccines.Laboratory tests to monitor the antigen content, purity, safety and immunogenicity seem to be the best approach to standardize this new generation of pertussis vaccines against homologous standard vaccines with known clinical efficacy and safety and to support the consistency in manufacture.

Reactogenicity and immunogenicity of reduced antigen content diphtheria–tetanus–acellular pertussis vaccines as a booster in 4–7-year-old children primed with diphtheria–tetanus–whole cell pertussis vaccine before 2 years of age

Background. The recent introduction of acellular pertussis vaccines (Pa) offers the possibility of booster doses in older children and adults. This can be conveniently accomplished by combining acellular pertussis antigens with diphtheria and tetanus toxoids. However the optimal dosage for the booster injection has not yet been determined. Objective. To compare the reactogenicity and immunogenicity of diphtheria–tetanus–acellular pertussis vaccines (DTPa) with lower antigen contents to a licensed DTPa vaccine when given at 4–7 years of age as a booster to DTPw-primed children. Methods. Two hundred and twenty-six children primed with four doses of DTPw before 2 years of age were enrolled and allocated to three groups to receive one dose of either DTPa (Infanrix™, SmithKline Beecham, Biologicals), a reduced antigen formulation of this vaccine (dtpa, SmithKline Beecham Biologicals), or an experimental low dose formulation (dtpa-exp; d and t, Michigan Biologic Products Institute). Reactogenicity was assessed using diary cards for 15 days. Immunogenicity was determined as antibody responses against the vaccine components in pre- and 1 month postvaccination sera. Results. Of the 225 children who completed the study, 60.0–66.7% reported symptoms, with no significant differences in rates between groups. Local, systemic and unsolicited symptoms occurred with similar frequencies in all three groups, the vast majority (>90%) being considered as mild or moderate. No serious adverse events related to vaccination were reported. After vaccination, all subjects displayed seroprotective concentrations against diphtheria and tetanus, and 98.7–100% had antibodies against the three pertussis component antigens. The group receiving the reduced dose of the licensed vaccine showed antibody concentrations comparable to those of the full dose group. However, the group receiving the experimental low dose formulation had statistically significantly lower antibody concentrations against both diphtheria and tetanus toxoids compared with the two other groups, as well as significantly lower anti FHA antibody concentrations. Conclusions. Reducing the antigen content of dtpa had no deleterious effect on the immunogenicity of the vaccine when given as a fifth dose at 4–7 years of age in DTPw-primed children. The reactogenicity profile of both the reduced antigen dtpa vaccines and DTPa were acceptable, the vast majority of local and systemic reactions being considered as mild to moderate, with no vaccine-related serious adverse events reported. The use of lower antigen content dtpa vaccine as a booster in children aged 4–7 is safe and immunogenic.

The effect of reconstitution of an Haemophilus influenzae type b-tetanus toxoid conjugate (PRP-T) vaccine on the immune responses to a diphtheria–tetanus-whole cell pertussis (DTwP) vaccine: a five-year follow-up

Controversial results have been obtained from previous studies on the combined administration of Haemophilus influenzae type b-tetanus toxoid conjugate (PRP-T) and diphtheria–tetanus-whole-cell pertussis (DTwP) combination vaccines, with regard to possible reciprocal interference between the constituent antigens. To document the priming effect and possible long-term immunogenic interference of PRP-T and DTwP combination vaccines, a randomized, double-blind, controlled study was conducted in Belgium. A total of 168 healthy infants received, at 3, 4 and 5 months of age, DTwP vaccine mixed just prior to injection either with PRP-T vaccine (group A, DTwP//PRP-T, N=85) or with placebo (group B, DTwP//Placebo, N=83). At the age of 14 months, children of both groups were randomized to receive either a dose of DTwP//PRP-T vaccine (subgroups A1 and B1) or a dose of Hib polysaccharide (PRP) vaccine (subgroups A2 and B2). Those children in subgroups A1 and B1 had an additional serum sample taken at the age of 5 years (at the time of a DT booster). The immune response to Hib polysaccharide at the age of 4, 5 and 6 months confirmed the excellent immunogenicity profile of PRP-T in infants. In addition, the vigorous anamnestic response (i.e. a 20-fold increase of GMT) to a booster dose of the plain capsular polysaccharide (PRP) reflected the efficient Hib-priming induced by the combined DTwP//PRP-T vaccine. Reconstitution of PRP-T with DTwP did not affect the immune response to diphtheria toxoid or pertussis agglutinins. Nevertheless, at almost any time point during the five-year follow-up, the tetanus antitoxin GMT values were significantly lower in the DTwP//PRP-T group (A and A1) than in the DTwP//Placebo group (B and B1). Despite the suppressive effect on GMT values, intergroup differences in rates of seroprotection were never significant, except after doses 2 and 3 for which there were lower percentages of children in group A with antitoxin titers >0.05 IU/mL and >1.0 IU/mL. In the group primed with the combined DTwP//PRP-T vaccine, (1) a DT booster dose at the age of 5 years provoked a 150-fold increase in tetanus antitoxin GMT, (2) a high tetanus antitoxin GMT value was attained (GMT=19.3 IU/mL) and (3) all children in this group had tetanus antitoxin titers >1.0 IU/mL, so it may be concluded that all these children will still be protected against tetanus until at least the age of the next recommended booster dose (i.e. the age of 15 years). No differences in the occurrence of adverse events were observed between the groups who received the DTwP//PRP-T vaccine or the DTwP//Placebo vaccine, both vaccines being associated with events customarily attributable to DTwP (data not shown). Our results indicate (1) that the combination vaccine, DTwP//PRP-T, represents a safe and effective alternative for the existing uncombined vaccines and (2) that the long-term effect of interference between the components of future combination vaccines should be studied with subsequent booster doses, followed by the evaluation of persistence of antibodies over several years.

Acellular vaccines for preventing whooping cough in children.

Routine use of whole cell pertussis vaccines was suspended in some countries in the late 1970s and early 1980s, leading to a resurgence of whooping cough. Acellular pertussis vaccines containing purified or recombinant Bordetella pertussis antigens were developed in the hope that they would be as effective but less toxic than the whole cell vaccines. The objective of this review was to assess the effects of acellular pertussis vaccines in children. The Cochrane Controlled Trials Register and Medline were searched up to January 1998. Double-blind randomised efficacy and safety trials of acellular pertussis vaccines in children, with active follow-up of participants and laboratory verification of pertussis cases. One reviewer assessed trial quality and extracted data. Six efficacy trials and 45 safety trials were included. Acellular pertussis vaccines with three or more pertussis vaccines were more effective than those with one or two antigens. They were also more effective than one type of whole cell pertussis vaccine, but less effective than two other types of whole cell vaccines. Differences in trial design precluded pooling of the efficacy data and results should be interpreted with caution. Most systemic and local adverse events were significantly less common with acellular than with whole cell pertussis vaccines. Multi-component acellular pertussis vaccines are effective, and show less adverse effects than whole cell pertussis vaccines. However in areas where whooping cough is more likely to be fatal, the higher toxicity of some whole cell vaccines may be offset by their increased effectiveness.