Issues in design of clinical trials of combination vaccines.
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Antibody Formation↗
Biomedical subjects
K M Edwards
Publications and source records attributed to K M Edwards.
Streptococcus pneumoniae colonization in the young child: association with otitis media and resistance to penicillin.
OBJECTIVE: To determine the nasopharyngeal colonization rate of penicillin-susceptible and penicillin-resistant strains of Streptococcus pneumoniae in young children, and to assess its relationship with the incidence of otitis media. DESIGN: Observational study in 215 children younger than 6 years of age who received care in the Vanderbilt Vaccine Clinic from September 1, 1992, to August 31, 1993. RESULTS: Of 842 nasopharyngeal cultures obtained, results for 44% of the cultures were positive for S. pneumoniae; 73% of the isolates were serotypes 6, 14, 19, or 23. Younger children had significantly higher rates of pneumococcal colonization than older children, with a peak at 1 year of age. By microdilution susceptibility testing, 37% of the cultures with positive results were intermediately or highly resistant to penicillin. Significantly more serotype 19 and 23 isolates were penicillin resistant than organisms of other serotypes. Children younger than 2 years of age had a twofold higher percentage of resistant isolates than those older than 2 years of age. A significant association was noted between nasopharyngeal carriage of S. pneumoniae and acute otitis media (p = 0.0002); however, the incidence of acute otitis media did not differ significantly between children colonized with penicillin-susceptible or penicillin-resistant strains. Unresolved otitis media was diagnosed more often in children who were colonized with resistant organisms than in children colonized with susceptible strains (p = 0.04). CONCLUSIONS: There was a high rate of nasopharyngeal carriage of penicillin-resistant S. pneumoniae in this population of young children. Nasopharyngeal colonization was associated with an increased incidence of acute otitis media, and penicillin resistance was associated with an increased incidence of unresolved otitis media.
Acute Disease↗
Efficacy and safety of pneumococcal revaccination after splenectomy for trauma.
OBJECTIVE: To assess the outcome of patient education after splenectomy and vaccination and to determine the safety and efficacy of pneumococcal revaccination 2 or more years after primary vaccination. MAIN OUTCOME MEASURES: Titers to serotype no. 6 and no. 23 pneumococcus and cutaneous and systemic reaction to revaccination. RESULTS: A total of 112 consecutive postsplenectomy patients receiving pneumococcal vaccine were identified; 45 were contacted and offered revaccination; 24 patients demonstrated a lack of understanding of the postsplenectomy state (unaware of splenectomy n = 2, unaware of splenectomy risk n = 8, unaware of vaccine n = 23); 3 patients had infections requiring hospitalization (pneumonia, strep throat and tonsillitis, pneumonia and bacteremia); 40 patients agreed to revaccination, and 33 patients returned for follow-up titers; 16 of 33 (48%) demonstrated at least a two-fold increase in at least one titer. Only 15% described the revaccination as worse than a tetanus shot. CONCLUSIONS: (1) Despite physician-patient conversations, pamphlets, and Medic Alert bracelets, patient retention was poor. (2) All splenectomy patients should be revaccinated and reeducated between two and six years after splenectomy. (3) Revaccination after two years was well tolerated. (4) There were no fatal episodes of pneumococcal sepsis in over 200 patient years.
Adult↗
Who should receive hepatitis A vaccine?
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Hepatitis A↗
Serologic responses to Bartonella and Afipia antigens in patients with cat scratch disease.
OBJECTIVE: To assess the serologic response to Afipia and Bartonella, previously named Rochalimaea, in patients with cat scratch disease (CSD) and a healthy control group. DESIGN: Prospective, controlled trial. SETTING: Referral clinic and hospitalized patients in a university medical center. PARTICIPANTS: Eighty patients with CSD and 57 healthy control subjects of similar age. MAIN OUTCOME MEASURES: The immune responses to Afipia felis and Bartonella henselae were evaluated by a newly developed enzyme-linked immunosorbent assay (ELISA) in patients with CSD and healthy control subjects. Responses to B henselae were also measured by indirect fluorescent antibody (IFA) tests. Antibody levels to Bartonella quintana were measured by ELISA and IFA in a limited number of patients and control subjects. RESULTS: Of the 80 patients with clinical CSD, 56 had positive results of CSD skin tests. ELISA antibody levels to A felis did not differ between patients and control subjects, but immunoglobulin M (IgM) and IgG ELISA antibodies to B henselae and B quintana were significantly higher in patients than in control subjects. IFA responses to B henselae and B quintana were also significantly higher in patients than in control subjects. CONCLUSION: Patients with CSD had significant serologic responses to B henselae and B quintana but not to A felis, suggesting that the causative agent of CSD is antigenically related to the Bartonella genus and not to Afipia. The Bartonella IgM ELISA and IFA assay were both sensitive and specific and may be used to establish the diagnosis of CSD.
Adolescent↗
Comparison of 13 acellular pertussis vaccines: overview and serologic response.
OBJECTIVE: To compare the immunogenicity of a licensed conventional whole-cell (WCL) and 13 diphtheria-tetanus-acellular pertussis (DTaP) vaccines that differed in source, method of manufacture, and included antigens; all vaccines included diphtheria and tetanus toxoids. METHODS: Healthy infants were enrolled through six university-based vaccine and treatment evaluation units and were randomized to receive one of the study vaccines at 2, 4, and 6 months of age. Sera were obtained before the first immunization and 1 month after the third immunization and were analyzed for antibody to pertussis toxin (PT), filamentous hemagglutinin, fimbriae, pertactin, and diphtheria and tetanus toxins. Chinese hamster ovary cell toxin neutralization assays were performed, and levels of agglutinating antibodies were determined. RESULTS: Of 2342 infants enrolled, 1942 contributed usable preimmunization and postimmunization serum specimens. Each vaccine produced significant increases in antibodies directed against the included antigens; postimmunization antibody titers differed significantly among the DTaP vaccines. For each evaluated antigen, the majority of DTaP vaccines produced antibody responses that equaled or exceeded those produced by WCL. For some antigens (eg, PT), mean antibody levels by vaccine correlated poorly with the quantity of antigen included in each vaccine; for others (eg., fimbriae), there was a close correlation. CONCLUSION: Although serologic correlates of pertussis immunity are not defined, it is clear that DTaP vaccines can stimulate immune responses that exceed those of licensed whole-cell vaccine with respect to the measured antibodies. Particularly for PT, immunogenicity seems to depend on factors in addition to antigen concentration, possibly including antigen derivation and formulation. No DTaP was most or least immunogenic with respect to all included antigens.
Antibodies, Bacterial↗
Comparison of 13 acellular pertussis vaccines: adverse reactions.
OBJECTIVE: To compare the reactogenicity of a licensed conventional whole-cell (WCL) and 13 acellular pertussis vaccines that differed in the source, manufacture, and quantity of included antigens; all vaccines included diphtheria and tetanus toxoids. METHODS: Healthy infants were enrolled through six university-based vaccine and treatment evaluation units and were randomized to receive one of the study vaccines at 2, 4, and 6 months of age. Parents recorded the occurrence of fever, redness, swelling, pain, fussiness, drowsiness, anorexia, and use of antipyretics for 2 weeks after each inoculation; nurses interviewed parents on the third day and at each succeeding visit; long-term follow-up information was collected from parents and medical records 1 year after the third immunization. RESULTS: Of 2200 vaccinated infants, 2189 contributed reaction data after 6375 vaccinations. For every acellular vaccine, every monitored reaction except vomiting occurred at a significantly lower frequency and severity than was seen with WCL. The groups receiving acellular pertussis vaccines differed significantly with respect to redness, swelling, pain, and vomiting, but not with respect to fussiness, antipyretic use, drowsiness, or anorexia. CONCLUSION: Although there were differences among the acellular vaccines, none was consistently the most or least reactogenic; all were associated with substantially fewer and less severe adverse reactions than a standard commercial whole-cell vaccine. Selection of acellular vaccines for further development and for introduction into efficacy trials can give priority to assessments of immunogenicity and purity, with comparative reactogenicity a secondary consideration.
Diphtheria-Tetanus-Pertussis Vaccine↗
A randomized comparison of reactogenicity and immunogenicity of two whole-cell pertussis vaccines.
OBJECTIVE: To compare prospectively the reactogenicity and immunogenicity of two licensed whole-cell pertussis vaccines. METHODS: We conducted a prospective, randomized, double-blinded assessment of two licensed whole-cell pertussis vaccines with diphtheria and tetanus toxoids that were included in a multicenter trial evaluating 13 acellular pertussis vaccines. Infants were immunized at 2, 4, and 6 months of age with a single lot of Lederle (309 infants) or Massachusetts Public Health Biologic Laboratories (MPHBL; 94 infants) vaccine. RESULTS: The group receiving the Lederle vaccine demonstrated significantly higher antibody titers to pertussis toxin by enzyme-linked immunosorbent assay (ELISA) and by the Chinese hamster ovary cell pertussis toxin neutralization assay, and to fimbrial antigens by ELISA, as well as higher mean agglutinin titers. In contrast, the group receiving the MPHBL vaccine demonstrated higher ELISA antibody levels to filamentous hemagglutinin and pertactin. Similar differences were observed in the proportions of vaccinees seroconverting to these antigens. Rates of systemic and local reactions were relatively low for both vaccines. Although the Lederle product had substantially lower reactogenicity in this study than previously reported for that vaccine, the MPHBL vaccine was significantly less reactogenic in nearly all clinical categories. CONCLUSION: The two whole-cell vaccines demonstrated statistically significant differences in postimmunization antibody levels to all six evaluated pertussis antigens. Whether these statistically significant differences in antibody levels have clinical relevance is not clear. Rates of nearly all local and systemic reactions were significantly lower among the MPHBL group than the Lederle group. Licensed whole-cell diphtheria-tetanus-pertussis vaccines produced by different manufacturers cannot be assumed to be similar in reactogenicity or immunogenicity.
Antibodies, Bacterial↗
Description and evaluation of serologic assays used in a multicenter trial of acellular pertussis vaccines.
OBJECTIVE: To describe and evaluate the assays used to measure the antibody responses in infants to 13 experimental acellular pertussis vaccines and 2 licensed whole-cell pertussis vaccines. METHODS: During a 53-week period, preimmunization and postimmunization sera were assayed for immunoglobulin G antibodies to pertussis toxin, filamentous hemagglutinin, pertactin, and a mixture of type 2 and type 3 fimbriae by enzyme-linked immunosorbent assay (ELISA), for whole-cell agglutinins (AGG), and for pertussis toxin-neutralizing antibodies by the Chinese hamster ovary cell assay. All ELISA reagents were characterized to assure antigen and isotype specificity of the assays. Intralaboratory reproducibility and temporal stability were evaluated by analysis of results of control sera and by assessment of the response to the control whole-cell vaccine. Interlaboratory reproducibility was assessed by repeating the assays on preimmunization and postimmunization sera for 10% of the infants in a second laboratory. RESULTS: For control sera having antibody concentrations at least four times the minimum level of detection, the coefficients of variation within and between the ELISAs consistently were less than 20%. Trend analysis indicated that none of the assays drifted by more than 20% during the study period, and no significant drift was seen in the response to the control whole-cell vaccine. Results from the two laboratories correlated well; correlation coefficients were .93 or greater for the four ELISAs, .79 for the Chinese hamster ovary cell assay, and .82 for the AGG assay. For four of the six assays, there was either no difference or a modest (< 15%) difference in the geometric mean values for sera tested in both laboratories. Larger quantitative differences were observed for the AGG (45% difference) and pertactin (61% difference) assays. CONCLUSION: Assay reproducibility and stability indicate that the standardized methods can be transferred between laboratories, and that the results accrued during a 1-year period for the 15 vaccines can be compared.
Agglutination Tests↗
Simultaneous administration of Haemophilus influenzae type b vaccine with acellular or whole-cell pertussis vaccine: effects on reactogenicity and immune responses to pertussis vaccines.
OBJECTIVE: To evaluate the effect of simultaneous Haemophilus influenzae type b conjugate (Hib) vaccination on the safety and immunogenicity of selected acellular (DTaP) and whole-cell (DTP) pertussis vaccines with diphtheria and tetanus toxoids combined. METHODS: Enrollment of infants into a large multicenter study of the safety and immunogenicity of 13 DTaP and 2 DTP vaccines was partially completed when the first Hib vaccine, HbOC (Haemophilus b oligosaccharide conjugate vaccine), was licensed for use in infants. Thereafter, at each immunization most infants received HbOC simultaneously with DTaP (or DTP), administered in opposite thighs. Postvaccination geometric mean titers or concentrations (GMTs) of pertussis antibodies as measured by six different assays were compared pairwise among groups of infants receiving 0, 1, 2, or 3 simultaneous HbOC immunizations. The incidence of reactions was compared between infants who received only DTaP or DTP and those who received HbOC simultaneously. RESULTS: Comparison of postvaccination GMTs was possible among groups of infants receiving different numbers of simultaneous immunizations for 10 of the 13 DTaP and both DTP vaccines. Increased HbOC exposure had no consistent dose-response effect on antibody titers for DTaP or DTP vaccines in any assay. Significant differences between groups in postvaccination GMTs were observed with 4 DTaP vaccines in 1 to 2 assays each; the GMTs were higher with increasing HbOC exposure for 2 DTaP vaccines and lower for 2 others. There was no significant increase in reactions with simultaneous HbOC and DTaP immunization. CONCLUSIONS: Based on these retrospective analyses, there did not seem to be an interference in pertussis immunogenicity or alteration in reactogenicity associated with the simultaneous administration of HbOC and DTaP. These findings are encouraging with respect to the development of DTaP-Hib combination vaccines.
Bacterial Proteins↗
The effect of maternal antibody on the serologic response and the incidence of adverse reactions after primary immunization with acellular and whole-cell pertussis vaccines combined with diphtheria and tetanus toxoids.
OBJECTIVE: To evaluate the effect of maternally derived antibody on the immunogenicity and reactogenicity of acellular (DTaP) or whole-cell (DTP) pertussis vaccine with diphtheria and tetanus toxoids combined. METHODS: A total of 2342 infants were randomized to receive one of 13 DTaP or 2 DTP vaccines at 2, 4, and 6 months of age. The correlation between preimmunization and postimmunization antibody after three doses of vaccine and the relation between preimmunization antibody and adverse reactions after the first immunization were modeled by linear regression. RESULTS: After DTP but not DTaP, higher levels of preexisting antibody were associated with substantial (28% to 56%) reductions in the subsequent antibody response to pertussis toxin (PT). For other pertussis antibodies, modest inverse correlations were seen between preexisting antibody concentrations and most postimmunization antibody responses (resulting in 8% to 18% reductions in postimmunization antibody) for both DTP and DTaP. There was no consistent association in any DTP or DTaP group between adverse reactions and preimmunization antibody levels. CONCLUSION: The PT antibody response to DTaP, unlike DTP, is not adversely affected by preexisting antibody to PT. Inhibitory effects with respect to other antibodies, seen with both DTP and DTaP, were relatively modest. Our data suggest that the use of acellular pertussis vaccines in adults, which could confer higher levels of antibody in women before pregnancy, would be unlikely to adversely affect pertussis antibody responses after DTaP among infants born to mothers with high antibody levels.
Antibodies, Bacterial↗
Effect of gender, race, and parental education on immunogenicity and reported reactogenicity of acellular and whole-cell pertussis vaccines.
OBJECTIVE: To determine whether gender, race (black or white), or level of parental education influenced serologic responses or reporting of clinical reactions after immunization with acellular (DTaP) or whole-cell (DTP) pertussis vaccine with diphtheria and tetanus toxoids combined. METHODS: Healthy infants were prospectively randomized to receive one of 13 DTaP, Lederle DTP, or another DTP. Parents recorded the occurrence of adverse reactions for 2 weeks after each inoculation. Sera obtained before the first immunization and 1 month after the third immunization were analyzed for antibody to pertussis toxin, filamentous hemagglutinin, fimbriae, and pertactin (PRN). Chinese hamster ovary cell pertussis toxin neutralization assays were performed, and levels of agglutinating antibodies determined. RESULTS: Prevaccination antibody levels did not differ by race, gender, or parental education. Postimmunization geometric mean titers (GMTs) were strongly and consistently associated with race. For both DTaP and DTP and for every included antigen, postimmunization GMTs were about twice as high for black as for white infants. Among DTaP recipients, these differences were significant for pertussis toxin, Chinese hamster ovary cell pertussis toxin neutralization assay, filamentous hemagglutinin, PRN, and agglutinins; among the much smaller sample of WCL recipients, the differences achieved or approached statistical significance for agglutinins, PRN, and fimbriae. These findings were confirmed by regression analyses that controlled for gender, parental education, study site, and preimmunization antibody level. Reported reactions were not correlated with parental education level and showed no material correlation with gender. Black infants were reported to have had more pain than white infants after receiving WCL and DTaP and were reported to be more fussy after receiving WCL. CONCLUSIONS: The consistently higher postimmunization GMTs among black infants seems to be a real finding for which we have no explanation; the infants did not significantly differ by race in vaccine assignment, preimmunization antibody levels, age at immunization, or interval from immunization to phlebotomy. These observations should be confirmed and further evaluated in future pertussis vaccine trials. Reported differences by race in pain and fussiness after receiving WCL might reflect chance, differences by race in the occurrence of reactions, or differences by race in the reporting of reactions.
Antibodies, Bacterial↗
Defining the key parameters for comparing reactions among acellular and whole-cell pertussis vaccines.
OBJECTIVE: To facilitate future vaccine reaction data collection and analysis, we sought to determine the minimum data set required to describe accurately and to compare common reactions after the administration of acellular (DTaP) or whole-cell (DTP) pertussis vaccine with diphtheria and tetanus toxoids combined. METHODS: Thirteen DTaP and 2 DTP vaccines were studied in a multicenter trial involving 2342 infants who received a primary series of vaccinations at 2, 4, and 6 months of age. Temperature, fussiness, redness, swelling and pain at the injection site, antipyretic use, drowsiness, loss of appetite, and vomiting were evaluated. Reactions were assessed at 3 hours and (if not immunized in the evening) 6 hours after immunization, at bedtime each evening for 7 evenings, and on the 14th evening after immunization. RESULTS: Two reaction assessment approaches were compared: (1) analysis of all reactions, regardless of the degree of severity; and (2) a condensation of the data to five key reactions (fever > 100 degrees F, moderate or more fussiness, any local redness, any local swelling, and moderate or more local pain). We found that the onset of reactions was infrequent beyond the second evening, and that collection and analysis of reaction data beyond that time did not further discriminate among the vaccines. Information regarding antipyretic use, loss of appetite, drowsiness, or vomiting did not assist in differentiating among these vaccines. CONCLUSION: Monitoring the occurrence of fever greater than 100 degrees F, moderate or severe fussiness, injection site redness or swelling, and moderate or severe injection site pain occurring through the second evening after immunization will provide the minimum data set needed to discriminate among DTaP and DTP vaccines with respect to the common adverse reactions.
Diphtheria-Tetanus-Pertussis Vaccine↗
Association of reactions after consecutive acellular or whole-cell pertussis vaccine immunizations.
OBJECTIVE: To evaluate the relative frequency of adverse reactions after initial and subsequent immunizations among infants receiving primary immunization with acellular (DTaP) or whole-cell (DTP) pertussis vaccine with diphtheria and tetanus combined. METHODS: We examined the occurrence of common reactions in 2127 infants within 48 hours after immunization at 2, 4, and 6 months with one of 13 DTaP or with Lederle DTP (WCL). Data on at least two consecutive immunizations were available for 357 WCL recipients and 1770 DTaP recipients. For these analyses, reactions evaluated included fever of 100.4 degrees F (38 degrees C) or greater, redness of 21 mm or larger, swelling of 21 mm or larger, moderate or severe pain, moderate or severe fussiness, loss of appetite, drowsiness, and vomiting. RESULTS: With one exception, reactions were approximately 1.5 to 8 times more likely to occur in WCL recipients if the same reaction had been observed at the previous immunization (the single exception was redness after the second immunization). Both initial and repeated reactions were less likely in DTaP than in WCL recipients. As with WCL recipients, risks of repeated reactions in DTaP recipients were higher than the risks of initial reactions (from 2.5 to 24 times as high). CONCLUSION: Reactions after a second or third immunization with either WCL or DTaP vaccine are more likely to occur in infants who had the same reaction after the preceding immunization. Absolute risks of repeated reactions tended to be lower after DTaP vaccine than after the WCL vaccine.
Diphtheria-Tetanus-Pertussis Vaccine↗
Detection of Rochalimaea henselae DNA by polymerase chain reaction from suppurative nodes of children with cat-scratch disease.
A polymerase chain reaction (PCR) assay was designed to amplify DNA from Rochalimaea henselae, Rochalimaea quintana and Afipia felis in the purulent material from lymph nodes in three patients with clinical cat-scratch disease (CSD) and two patients with lymphadenitis from other causes. All of the patients with CSD had positive immunofluorescent antibody serology for R. henselae, while none of the controls was positive. PCR amplification confirmed the presence of R. henselae DNA and the absence of R. quintana and A. felis DNA in the purulent material from CSD patients. PCR samples from control patients were negative. The PCR amplification of R. henselae DNA was performed quickly and with great sensitivity and specificity. It confirmed the presence of R. henselae in the CSD patients and eliminated the need for more extensive diagnostic and therapeutic procedures.
Bartonella henselae↗
Impact of Haemophilus influenzae type b polysaccharide-tetanus protein conjugate vaccine on responses to concurrently administered diphtheria-tetanus-pertussis vaccine.
OBJECTIVE: To assess whether serum antibody responses to diphtheria-tetanus-pertussis (DTP) vaccine were affected by coadministration of Haemophilus influenzae type b capsular polyribosylribitol phosphate polysaccharide-tetanus protein (PRP-T) conjugate vaccine when given to patients at 2, 4, and 6 months of age. DESIGN: Randomized, double-blind clinical trial. SETTING: Urban Santiago, Chile. PATIENTS: Healthy infants assembled from health centers. Two hundred seventy-eight (74%) of 375 eligible infants participated; 222, who complied with the complete protocol, constituted the primary group under analysis. INTERVENTIONS: One of three vaccine regimens was given to study participants at 2, 4, and 6 months of age, either DTP mixed in the same syringe as PRP-T (group 1); DTP and PRP-T given at separate injection sites (group 2); or DTP without PRP-T (group 3). PRIMARY OUTCOME MEASURES: Titers of serum antidiphtheria toxoid, antitetanus toxoid, and pertussis agglutinin antibodies were measured in blood samples taken from patients 2 months after each dose. RESULTS: Serum antidiphtheria toxoid and antitetanus toxoid responses showed no important depressions in the patients receiving PRP-T. In contrast, geometric mean titers (GMTs) of pertussis agglutinins, expressed as reciprocal serum dilutions, after both the second and third doses (GMT2, GMT3) were lowest in group 1 (GMT2 = 89; GMT3 = 1230), intermediate in group 2 (GMT2 = 123; GMT3 = 1995), and highest in group 3 (GMT2 = 210; GMT3 = 3090; P less than .05 for trend group 1 less than group 2 less than group 3 after each dose). Antipertussis toxin and antipertussis filamentous hemagglutinin antibody titers also were depressed in patients who received PRP-T. Follow-up of a subset at 18 months revealed an expected decline of pertussis agglutinin titers to near baseline levels in each group. CONCLUSIONS: Concurrent administration of PRP-T vaccine with DTP vaccine, either in the same syringe or at different sites, interfered with antipertussis responses to a primary series of immunizations. Although the clinical significance of this antagonism is uncertain, these data underscore the caution required in decisions to add new vaccines to existing immunization regimens.
Antibodies, Bacterial↗
Comparative trial in infants of four conjugate Haemophilus influenzae type b vaccines.
We performed a double-blind, randomized trial to compare the immunogenicity and reactogenicity of four conjugate Haemophilus influenzae type b vaccines given to infants 2, 4, and 6 months of age. Adverse reactions attributable to the vaccines were few and minor. The rates of systemic reactions did not differ among the various vaccines and were similar to those seen among children receiving conventional diphtheria-tetanus-pertussis vaccine. However, the four conjugate H. influenzae type b vaccines differed markedly in ability to stimulate antibody production. Mean antibody levels after three injections of polyribosylribitol phosphate conjugated with mutant diphtheria protein (PRP-CRM) or polyribosylribitol phosphate conjugated with tetanus toxoid (PRP-T) were 3.08 micrograms/ml and 3.64 micrograms/ml, respectively, significantly higher than those after the use of polyribosylribitol phosphate conjugated with outer-membrane protein of Neisseria meningitidis (PRP-OMP) (1.14 micrograms/ml) or polyribosylribitol phosphate conjugated with diphtheria toxoid (PRP-D) (0.28 microgram/ml). Only PRP-OMP produced a clinically pertinent elevation in antibody level after two injections (0.84 microgram/ml); the third injection of PRP-OMP produced a modest but statistically significant further elevation in mean antibody level (1.14 micrograms/ml). Only 29% of infants receiving PRP-D had antibody levels of 1 micrograms/ml, compared with 55%, 75%, and 83% of those receiving PRP-OMP, PRP-CRM, and PRP-T, respectively. We conclude that all four vaccines are safe and that all but PRP-D appear appropriate for use in a primary immunization series during infancy. The unique serologic response to PRP-OMP offers both advantages and disadvantages in comparison with PRP-CRM and PRP-T.
Antibody Formation↗
Safety and immunogenicity of live attenuated cold-adapted influenza B/Ann Arbor/1/86 reassortant virus vaccine in infants and children.
A cold-adapted (ca) influenza B reassortant vaccine consisting of two genes encoding the hemagglutinin and neuraminidase from wild-type influenza B/Ann Arbor/1/86 virus and the six internal RNA segments from influenza B/Ann Arbor/1/66 ca virus was evaluated in 18 seropositive and 57 seronegative infants and children. The ca reassortant was infectious in seronegative vaccinees, with an estimated 50% human infectious dose of 10(2.5) TCID50. Nasal wash specimens from vaccinees retained the temperature-sensitive phenotype, indicating that the virus was phenotypically stable after replication in fully susceptible children. The vaccine was highly immunogenic in the seronegative vaccinees; 54% of the seropositive vaccinees also developed an increase in serum antibody. The ca vaccine was well tolerated, with only a mild increase in upper respiratory tract symptoms seen in the seronegative vaccinees. These studies indicate that the B/Ann Arbor/1/86 ca reassortant is safe, immunogenic, and phenotypically stable in infants and children.
Antibodies, Viral↗