The agglutinin response to whole-cell and acellular pertussis vaccines is Bordetella pertussis--strain dependent.

OBJECTIVE--To determine the significance of the Bordetella pertussis strain used as the antigen in the agglutinin assay for the evaluation of pertussis vaccines. DESIGN--Randomized, double-blind study. SETTING--Health maintenance organization clinics, primary care clinic at a referral hospital, and private practices in Los Angeles County, California. PARTICIPANTS--Forty healthy infants. SELECTION PROCEDURES--Convenience sample. INTERVENTIONS--Twenty infants received whole-cell pertussis-component diphtheria-tetanus-pertussis vaccine (DTP), and 70 infants received acellular pertussis-component diphtheria-tetanus-pertussis vaccine (APDT) at ages 2, 4, and 6 months. MEASUREMENTS--The agglutinin assay was performed using three separate B pertussis strain preparations: (1) strains 130 and 138 in equal quantities, the constituents of the DTP vaccine, (2) strain 460, and (3) strain Tohama, the constituent of the APDT vaccine. RESULTS--The agglutinin titers were highly strain dependent; in both groups of vaccinees at both ages the Tohama values were highest, followed by strain 460 and then strains 130/138. The vaccine groups had comparable titers at age 2 months regardless of the assay antigen used. However, at age 7 months, after three immunizations, the DTP group geometric mean titer was more than 10 times greater than that of the ADPT group using strains 130/138, but only 2.6 times higher using strain 460 and almost equivalent using Tohama strain. CONCLUSION--Vaccine group agglutinin value comparisons strongly depend on assay antigens used.     

Differences in antibody response to whole-cell pertussis vaccines

It has been assumed that whole-cell pertussis vaccines (WCVs) commercially distributed in the United States are of comparable immunogenicity, as all must comply with established standards for licensure. However, we have recently noted significant differences in antibody responses between groups of infants receiving the two WCVs commercially available in the United States. In separate studies performed concurrently under similar protocols at Vanderbilt and Johns Hopkins universities, infants were randomized to receive either an acellular pertussis vaccine or WCV. The acellular pertussis vaccine used at the two sites was identical, but the WCVs were from different manufacturers. Antibody responses to acellular pertussis vaccine did not differ between the two studies; responses to WCV differed dramatically, with infants receiving the Lederle WCV producing a 46-fold increase in antibody to pertussis toxin, compared with a 2.4-fold increase for infants receiving the Connaught WCV (P = .00003). Evaluation of other comparative data sets that were available provided further support for the conclusion that the two commercially available WCVs consistently differed in their ability to induce antibody to pertussis toxin. These findings have important implications for the design and interpretation of clinical trials comparing acellular and WCV products.     

Antibody levels to Bordetella pertussis in 10-yr-old children with atopy and atopic asthma

Suboptimal immune responses to vaccination have been suggested among atopic infants. The aim of this study was to assess the influence of atopy and atopic asthma on the humoral response to Bordetella pertussis vaccination. Immunoglobulin (Ig)G and IgA specific antibodies were measured by enzyme linked-immunosorbent assay in 102, 10-yr-old atopic children (66 of them also being asthmatics) and compared with 76 non-atopic and 53 non-atopic non-asthmatic controls of similar age. The levels of antibodies and the percentage of positives to B. pertussis were comparable in all groups. Children with a very high total serum immunoglobulin (Ig)E (Percentile (Pct) > 90th) showed higher (p = 0.01) IgG pertussis antibodies than children with very low serum IgE (Pct < 10th). In conclusion, we found normal pertussis antibody levels in atopic and in atopic asthmatic children in late childhood, thus overriding any possible suboptimal response during infancy.     

Cell-mediated immune responses to antigens of Bordetella pertussis and protection against pertussis in school children

BACKGROUND: Increasing evidence suggests that cell-mediated immunity (CMI) is involved in immune response against Bordetella pertussis. However, there are practically no studies evaluating the significance of pertussis-specific CMI in relation to protection against clinical pertussis. METHODS: An outbreak of pertussis was studied prospectively in 13-year-old pupils in a rural school. B. pertussis infection was diagnosed by culture, microagglutination and enzyme immunoassay serology with the use of pertussis toxin, filamentous hemagglutinin and pertactin as antigens. Pertussis-specific CMI responses were assessed by in vitro proliferation assay of peripheral blood mononuclear cells. RESULTS: At the initial sampling 7 of 22 children had symptoms suggestive of pertussis and 15 were asymptomatic. Of the latter 3 remained healthy, 8 were later confirmed to have had asymptomatic infection, 3 developed laboratory-confirmed pertussis and 1 developed cough without laboratory evidence of pertussis. Initial in vitro proliferations of peripheral blood mononuclear cells induced by pertussis toxin, filamentous hemagglutinin and/or pertactin were positive in all 3 healthy children, in 6 of 8 children who had asymptomatic infection, but in none of the 3 children who later developed pertussis. Although some children who remained healthy had high values of antibodies, no clear association was found between initial serum antibody values and clinical outcome. CONCLUSIONS: These preliminary data suggest that CMI may have an important role in protection against clinical pertussis but do not exclude a role for antibodies. Furthermore the results stress a multifactorial nature of the immune protection against B. pertussis.     

Brain damage from pertussis immunization. A Canadian neurologist's perspective.

Uncontrolled case series noting an association between diphtheria, tetanus, and pertussis vaccine (DTP) immunization and brain damage have lead to widespread reduction in immunization, epidemics of pertussis and litigation. A judge, hearing the only Canadian court case, concluded there is no evidence that DTP induced brain injury. It is difficult to develop a cogent biologic hypothesis for the mechanism of DTP-induced brain injury, especially when the postulated clinical syndrome is variable without a characteristic neuropathologic pattern. Timed observational, case-controlled, and prospective cohort studies have not shown evidence of brain damage from pertussis vaccine. This suggests that the cause(s) of brain injury recorded in case series was other than DTP immunization. Any relationship is likely a temporal coincidence because DTP is administered several times in infancy. A vigorous effort is required to dispel the myth of DTP-induced brain damage.     

Antibody response to poliovirus immunization in childhood leukemia.

Polio antibody titers were determined in 29 children with ALL in various clinical stages, including a group of five patients in continuous remission for over five years and who, at the time of study, were off all therapy for at least six months. Regardless of the stage of disease, no detectable gamma M response was elicited. The five children described above displayed the same depressed response as did the other children with ALL. This strongly suggests an inherent defect in the immune system of these children with ALL unrelated to therapy.     

Antibody response to poliovirus immunization in childhood leukemia

Polio antibody titers were determined in 29 children with ALL in various clinical stages, including a group of five patients in continuous remission for over five years and who, at the time of study, were off all therapy for at least six months. Regardless of the stage of disease, no detectable YM response was elicited. The five children described above displayed the same depressed response as did the other children with ALL. This strongly suggests an inherent defect in the immune system of these children with ALL unrelated to therapy.     

Antibody response to live virus vaccines in congenital and neonatal cytomegalovirus infections.

When 42 infants with congenitally or neonatally acquired cytomegalovirus infections were one year of age, they were given live attenuated measles-mumps-rubella combined vaccine to determine what effect, if any, the existence of chronic CMV infection has on the antibody response to measles and rubella antigens. When the infected infants were compared with 60 healthy non-CMV-infected control infants, no significant difference in the seroconversion rates or ultimate antibody levels was observed with either measles or rubella antigens. Persistence of antibody, when measured three years after vaccination, was likewise similar in each group; levels had waned only slightly. These results demonstrate the intactness of humoral immunity in children with pre- and perinatal CMV infection.     

Antibody persistence after primary immunization with trivalent oral poliovirus vaccine.

Five years after primary infant immunization with trivalent oral poliovirus vaccine, employing either a three-dose primary series as recommended by the U.S. Public Health Service Advisory Committee on Immunization Practices (ACIP) or a four-dose series as recommended by the Committee on Infectious Diseases of the American Academy of Pediatrics. 115 children were serologically tested for persistence of neutralizing antibodies by the microneutralization test. Of the 57 individuals immunized according to the ACIP recommendation, antibody persistence was demonstrated in 92% for type 1 poliovirus, 98% for type 2, and 84% for type 3. Of those 58 individuals originally receiving a four-dose primary infant immunization series, the persistence of antibody was 98% to type 1, 98% to type 2, and 87% to type 3. Twenty-one of 24 negative sera showed neutralizing ability when tested by a more sensitive plaque reduction test. Thus, individuals completing either immunization schedule demonstrated satisfactory persistence of neutralizing antibody to all three poliovirus types over a five-year period.     

Local reactions and IgE antibodies to pertussis toxin after acellular diphtheria-tetanus-pertussis immunization

Local reactions and pertussis toxin specific immunoglobulin E antibodies (PT-IgE) were investigated in healthy children following primary and booster immunization with a combined diphtheria tetanus acellular pertussis vaccine (DTPa) including pertussis toxin, filamentous haemagglutinin and pertactin. A primary series of DTPa was administered to 150 infants, and 104 of them received a booster dose of DTPa combined with inactivated polio vaccine at 2 years of age. PT-IgE was measured in serum samples from 72 children using a modified nitrocellulose RAST. Primary immunization was associated with low incidence of local reactions (1%–5%). After the booster dose 21% of children had a local reaction ≥20 mm. Local reactions after the booster dose tended to be more common in children who had experienced reaction at primary immunization. PT-IgE was detected in 18% and 86% of children following primary and booster vaccinations, respectively. Allergic and non-allergic children did not differ in PT-IgE responses. After primary immunization, elevated PT-IgE levels were found more often in children with a family history of allergy than in those without known allergy in the family. Children with local reactions had significantly higher pre- and post-booster PT-IgE levels and median post-booster pertactin IgG and diphtheria-IgG levels than children without local reactions. Conclusion Acellular pertussis immunization induces IgE antibodies to pertussis toxin, especially after booster vaccination. The higher median pre- and post-booster levels of pertussis toxin specific immunoglobulin E and post-booster levels of IgG to pertactin and diphtheria in children with local side-effects reflect a multifactorial immunological mechanism of such reactions. Received: 21 May 1999 / Accepted: 13 June 1999     

Immunogloblin E and G responses to pertussis toxin after booster immunization in relation to atopy, local reactions and aluminium content of the vaccines

The role of aluminium for IgG and IgE responses to pertussis toxin (PT), as well as for side effects, was investigated in 49 children with known atopy status. Primary immunization had been given with an adsorbed monocomponent or an adsorbed two-component acellular pertussis vaccine. The children were then randomized to receive a booster immunization with either aluminiumadsorbed or non-adsorbed, whole cell, pertussis vaccine. Both vaccines induced good IgG responses with the adsorbed vaccine giving higher post-booster levels (p < 0.05). The adsorbed vaccine was, however, associated with more local side effects (p < 0.05) and tended to induce higher PT-IgE responses than the non-adsorbed vaccine. Furthermore, individuals who had received the two-component vaccine as primary immunization had higher PT-IgE responses after the booster, compared with individuals initially receiving the monocomponent vaccine (p = 0.041). No correlation between PT-IgE and PT-IgG levels was seen in any of the groups. Total serum IgE levels correlated to PT IgE levels, particularly in children with atopy (r = 0.950, p < 0.001). The addition of aluminium to the pertussis vaccine, was, thus, associated with a stronger IgG antibody response, but tended also to induce a stronger IgE antibody response. The correlation between total IgE and PT-IgE, which was most prominent in children with atopy, indicates that the role of immunization for the development of allergy merits further studies.     

Booster response to acellular pertussis vaccine in children primed with acellular or whole cell vaccines

Few data are available on the effect of a booster dose of acellular pertussis vaccine in children primed as infants with acellular vaccine. We administered acellular pertussis vaccine (ACV) at 19 months to children immunized in infancy with ACV or whole cell vaccine. Forty-one infants had been randomly assigned to receive either ACV or whole cell vaccine at 2, 4 and 6 months of age. Antibody titers to pertussis toxin and filamentous hemagglutinin were significantly higher in ACV than whole cell vaccine recipients at 7 months; at 15 months antibody to filamentous hemagglutinin (but not pertussis toxin) remained significantly higher among those receiving ACV. At 19 months all 41 children received an ACV booster. Local and systemic reactions were few and minor and were equally distributed between the two groups. All children responded to booster with significant increases in antibody; these increases tended to be greater for those having been primed with ACV. ACV booster immunization appears safe and immunogenic, regardless of the vaccine given for primary immunization.     

Clinical and epidemiological picture of B pertussis and B parapertussis infections after introduction of acellular pertussis vaccines.

AIMS: To investigate the clinical picture and frequency of Bordetella pertussis and B parapertussis infections after introduction of acellular pertussis (acP) vaccines in Germany. METHODS: Prospective surveillance for B pertussis and B parapertussis in 14 144 toddlers. Pertussis vaccination coverage was 86%, either with acP (75%) or whole cell pertussis (wcP) vaccine (11%). All children presenting with cough for more than seven days were examined for B pertussis and B parapertussis by culture, PCR, and serology (for cough duration > or =21 days). RESULTS: There were 180 Bordetella infections; 116 (64%) were caused by B pertussis and 64 (36%) by B parapertussis. Incidence rates were 4.8 and 2.8 per 1000 person-years, respectively. Paroxysmal cough, post-tussive whooping, and vomiting > or = 21 days was found in 53%, 22%, and 8% of all B pertussis cases and in 22%, 5%, and 0% of all B parapertussis cases, respectively. A total of 81/116 (70%) B pertussis cases and 56/64 (87.5%) B parapertussis cases had received at least one dose of pertussis vaccine. Typical pertussis with paroxysmal cough > or = 21 days was present in 29/35 (83%) unvaccinated B pertussis cases, in contrast to 33/81 (41%) vaccinated B pertussis cases. CONCLUSION: Following the increase of pertussis vaccination coverage, we observed a relative increase of B parapertussis cases in comparison to B pertussis cases. In vaccinated children B pertussis disease frequently presented as a mild disease, clinically difficult to distinguish from diseases associated with coughing caused by B parapertussis and other viral or bacterial infections.     

Thrombocytopenia after immunization of Canadian children, 1992 to 2001

BACKGROUND: Thrombocytopenia occasionally follows immunization of children, especially after administration of measles-containing vaccines. The purpose of this study was to describe the clinical features of postimmunization thrombocytopenia, with emphasis on the rate of complications and outcome. METHODS: A prospective survey was conducted by 12 pediatric centers in Canada during 1992 to 2001. At each center a nurse monitor searched for inpatient cases. Cases were defined as having onset of clinical signs or laboratory measures of thrombocytopenia (platelet count, <50 x 10(9)/l) within 30 days after immunization. Cases were described in a standardized manner, including follow-up data as available. RESULTS: Sixty-one cases were detected, an average of 6 per year or approximately 1 case per 15,000 general hospital admissions. Median age of cases was 13 months. The mean platelet count at diagnosis was 8.6 x 10(9)/l. Most cases (79%) followed measles-containing vaccines. Only 1 child had a serious (fatal) complication. Platelet counts returned to normal within 30 days of onset in 46 of 57 children (80.7%) with information available. Five children (8.2%) had persistent or intermittent thrombocytopenia for 3 months or more. CONCLUSION: Thrombocytopenia associated with routine immunization of children is rare and usually benign, resolving within 1 month in most children.     

Update on adolescent immunization: review of pertussis and the efficacy, safety, and clinical use of vaccines that contain tetanus-diphtheria-acellular pertussis.

Adolescents, who comprise 14% of the US population, are historically resistant to receiving health care. As a result, adolescents have low immunization rates and are becoming more susceptible to diseases that are preventable by vaccine, such as pertussis. The incidence of pertussis has increased during the past 25 years, with a notable shift in incidence from young children to adolescents and young adults. New vaccines that provide protection against pertussis for use in adolescents have been proven to be safe, effective, and cost-beneficial. Regional epidemics among infants and other vulnerable populations can be reduced or eliminated with improved immunity in adolescents.