Safety and immunogenicity of live attenuated quadrivalent human-bovine (UK) reassortant rotavirus vaccine administered with childhood vaccines to infants.

The safety and immunogenicity of an orally administered, live rotavirus vaccine comprised of four strains, each with a titer of 10(5.3) or 10(5.8) pfu, and each having 10 genes from the UK bovine strain and the VP7 gene from human rotavirus serotype 1, 2, 3, or 4, were evaluated in adults, young children and infants in randomized, double-blind phase 1 trials. Three doses of rotavirus vaccine or placebo given with childhood immunizations to infants at 2, 4, and 6 months of age were well tolerated and did not inhibit antibody responses to childhood vaccines which included DTP, Hib, hepatitis B and OPV. Serum rotavirus antibody responses were detected in 12 of 20 infants after 1 dose, and in 19/19 of the vaccinees after three doses. Neutralizing antibody responses were detected more often against the bovine rotavirus UK strain (95%) than to human rotavirus VP7 serotypes 1 (37%), 2 (32%), 3 (32%) or 4 (32%). The efficacy of this quadrivalent rotavirus vaccine needs to be evaluated further.

Immunogenicity of tetanus-diphtheria toxoids (Td) among Ukrainian adults: implications for diphtheria control in the Newly Independent States of the Former Soviet Union.

After 30 years of control, epidemic diphtheria returned to the Soviet Union in 1990. To develop control strategies, the immunogenicity of the tetanus and diphtheria toxoids (Td) vaccine was assessed. Workers who were 18-67 years old received two Td immunizations separated by 30 days. A neutralization assay determined diphtheria antitoxin (DAT) on enrollment and on days 7, 30, 60, and 425. On enrollment, 43.0% of 488 workers had DAT <0.1 IU/mL. After one dose, 88.5% had DAT >/=0.1 IU/mL, after two doses, 92.2% had >/=0.1 IU/mL and >90% of participants <30 or >/=50 years of age attained >/=1.0 IU/mL; however, only 78.4% of those who were 30-39 years old and 51.8% of those who were 40-49 years old achieved >/=1.0 IU/mL after two doses. To control the epidemic in Ukraine, one Td dose should be administered to virtually the entire population (persons 30-49 years old require three doses of Td for optimal individual protection and to maximize population immunity).

Evaluation of a single dose of diphtheria toxoid among adults in the Republic of Georgia, 1995: immunogenicity and adverse reactions.

To determine the immunogenicity and safety of a single dose of diphtheria toxoid among adults, blood samples for detecting serum antitoxin levels were obtained from 18- to 59-year-old subjects (n=248) before and 30 days after immunization with Td (tetanus-diphtheria toxoids; manufactured by Serum Institute of India). By day 30, the seroprevalence of antitoxin levels >/=0.1 IU/mL increased from 22.6% to 81.5%; median antitoxin levels increased from 0.01 to 4.0 IU/mL. These parameters were lowest among subjects who were 40-59 years old, especially among those 40-49 years old. Adverse reactions (local redness, swelling, induration, fever>39 degrees C) were reported by 5.3% of participants. Our findings suggest that, in general, one dose of the Indian-produced Td vaccine is efficacious and safe in inducing an adequate immune response against diphtheria in adults; however, in Georgia, persons 40-59 years old, especially those 40-49 years old, will require additional doses of toxoid to achieve protective levels of antitoxin.

Evaluation of a single dose of diphtheria-tetanus toxoids among adults in Odessa, Ukraine, 1995: immunogenicity and adverse reactions.

Epidemic diphtheria spread to Ukraine in 1991, where it peaked in 1995 with >5,000 reported cases. To refine epidemic control strategies, immunogenicity of a tetanus-diphtheria toxoids vaccine (Td) containing 2 limits of flocculation (Lf) diphtheria toxoid was evaluated. During a mass vaccination campaign, adults at a clinic in Odessa received one dose of Td. At enrollment, 57.2% of 341 study participants had levels of diphtheria antitoxin (DAT) >/=0.1 IU/mL. Thirty and 180 days after receiving one dose of Td, 91.5% and 84.5% of the participants, respectively, had DAT levels >/=0.1 IU/mL. However, among 40- to 49-year-old participants, only 78.8% and 73.8% had DAT levels >/=0.1 IU/mL at 30 and 180 days, respectively. This study suggests that one dose of 2 Lf diphtheria toxoid is highly effective in raising DAT to protective levels in most adults; however, the study also shows that certain age groups, particularly persons 40-49 and, to a lesser degree, 30-39 years old may require additional doses or a complete three-dose primary vaccination series for optimal protection against diphtheria.

Dose-response to a two-component acellular pertussis vaccine in infants and comparison with whole-cell vaccine.

In an effort to determine the optimal dose of pertussis toxoid (PT) and filamentous haemagglutinin (FHA) for use in acellular pertussis vaccines we compared the immunogenicity and safety of acellular pertussis vaccine combined with diphtheria and tetanus toxoids containing 12.5 microg (DTaP-12.5) or 25 microg (DTaP-25) each of PT and FHA with a whole cell pertussis vaccine in infants immunized at 2, 4 and 6 months of age. Recipients of acellular vaccines developed higher anti-FHA concentrations and more rapid anti-PT serological responses that infants who received whole cell pertussis vaccine combined with diphtheria and tetanus toxoids (DPT). A dose response was noted; infants immunized with DTaP-25 developed significantly (P<0.03) higher anti-FHA and anti-PT levels than infants who received DTaP-12.5. No rise in the agglutinin titres was noted for recipients of the acellular vaccines although this vaccine stimulated increases in agglutinins when given as the fourth or fifth dose to children who had received three doses of DTP. The rates of erythema, induration, pain, irritability, crying, increased sleepiness, and decreased appetite were significantly (P

Immunity to diphtheria in a sample of the Canadian adult population.

OBJECTIVE: To assess immunity to diphtheria in a sample of Canadian adults. DESIGN: A seroprevalence study of a group of plasmapheresis donors was performed over a four-month period in 1996. A convenience sample of 1619 sera was collected to obtain a good distribution by age groups and centres. The determination of diphtheria antitoxin concentrations was performed by neutralization of diphtheria toxin in cell culture. SUBJECTS: A total of 1619 plasmapheresis donors from Halifax, Quebec City, London, Calgary and Edmonton were studied. RESULTS: Of the 1619 sera, 20.3% tested showed susceptibility to diphtheria (antitoxin concentration less than 0.01 IU/mL). The proportion of susceptibles increased from 9.5% in subjects 30 to 39 years of age to 36.3% in those 60 years of age or more. The age group 20 to 29 years demonstrated a higher proportion of susceptibles (18.3%) than the next age group (30 to 39 years) in four of the five centres. Significant differences in antibody levels were also observed among the centres. There was no statistically significant difference between sexes. CONCLUSIONS: Overall, detectable antibody and presumably immunity to diphtheria in the present sample of Canadian adults is relatively good. However, reason(s) for the relatively high proportion of susceptibles in those aged 20 to 29 years of age in certain centres, as well as why Canada has not experienced any diphtheria outbreaks in the past 20 years given these susceptibility levels, should be investigated further.

Response to the varicella vaccine in children with nephrotic syndrome.

Varicella vaccine was administered to seven children with corticosteroid-sensitive nephrotic syndrome. Immunization was not associated with any significant reactions or with increased frequency of relapse. The antibody response was, however, variable and a second dose was necessary before seroconversion was achieved in four patients. The findings indicate that immunization with varicella vaccine is safe in children with nephrotic syndrome in remission, but that a two-dose vaccine schedule should be considered.

A safety and immunogenicity comparison of 12 acellular pertussis vaccines and one whole-cell pertussis vaccine given as a fourth dose in 15- to 20-month-old children.

OBJECTIVE: To compare the safety and immunogenicity of 12 different acellular pertussis vaccines combined with diphtheria and tetanus toxoids (DTaP) with one licensed diphtheria, tetanus, and whole-cell pertussis vaccine (DTwP) as a fourth-dose booster in children who had previously received DTaP or DTwP primary vaccinations. METHODS: Healthy 15- to 20-month-old children were enrolled at six National Institutes of Health Vaccine Treatment and Evaluation Units. All had been randomly assigned to receive three primary doses of DTaP or DTwP at 2, 4, and 6 months of age as part of an earlier National Institutes of Health multicenter trial of DTaP vaccines in the same Vaccine Treatment and Evaluation Units. Parents recorded the occurrence and magnitude of fever; irritability; and injection site redness, swelling, and pain for 3 days after vaccination. Sera obtained before and 1 month after the booster vaccination were analyzed for antibody to pertussis toxin (PT), filamentous hemagglutinin (FHA), fimbriae (FIM), and pertactin (PRN). Diphtheria and tetanus toxoid as well as PT neutralizing (Chinese hamster ovary cell) and whole-cell agglutinating antibodies were measured on a subset of sera. RESULTS: A total of 1293 children contributed fourth-dose reaction data. Reactions were less frequent after DTaP than after DTwP. For children vaccinated with a fourth dose of DTaP, which was the same DTaP as received in the primary series, fever and injection site redness, swelling, and pain increased in prevalence compared with the third dose in the primary series. For children receiving DTaP as a fourth dose, injection site redness and swelling occurred more frequently in DTaP-primed than in DTwP-primed children. Variation in the occurrence of reactions among DTaP vaccines was observed. A total of 1160 paired pre- and postvaccination sera were available for analysis. Serum antibody concentrations before boosting were lower than those obtained 1 month after the primary immunization. After the fourth dose, significant increases in antibodies directed against the included antigens were observed for all vaccines; postbooster vaccination antibody titers differed significantly among the DTaP vaccines. For children primed and boosted with the same DTaP, antibody levels were not directly related to the quantity of antigen included for PT, FHA, and FIM; for PRN, there was a closer relationship. Some DTaP vaccines given as fourth-dose boosters elicited antibody to PRN or FIM in some vaccinees, although the DTaP vaccines were not reported to contain these antigens; these responses were observed more frequently in DTwP-primed children. Agglutinin antibody rises were observed in all groups immunized with four doses of a DTaP vaccine containing FHA or PRN, regardless of whether the vaccine included FIM. Diphtheria and tetanus antibody levels exceeded the presumed protective concentration (0.1 IU/mL for diphtheria and 0.01 IU/mL for tetanus) after the fourth dose for all vaccinees. CONCLUSION: Although differences were observed in reaction rates among the DTaP vaccines given as a fourth dose, the DTaP vaccines were, in general, associated with fewer adverse events than a US-licensed DTwP. For DTaP vaccines, fever; irritability; and injection site pain, redness, and swelling occurred more frequently after the fourth dose than after the third dose of the same vaccine in the primary series. No DTaP was consistently most or least reactogenic or immunogenic. Although serologic correlates of pertussis immunity are not defined, it is clear that most DTaP vaccines can stimulate comparable or higher serum antibody responses than DTwP for those antigens contained in the vaccine.

Intravenous immunoglobulin prophylaxis of cytomegalovirus infection in pediatric renal transplant recipients.

Cytomegalovirus (CMV), the most significant infectious cause of morbidity following renal transplantation, may be a greater problem for children than for adults due to their relative lack of experience with this virus. Therefore, we prospectively gave Gammagard as prophylaxis to CMV-negative children who received CMV-positive allografts and compared the results to our experience with similar high-risk recipients transplanted prior to our use of intravenous immunoglobulin G (IvIgG). Symptomatic CMV disease developed in 17% of the IvIgG recipients as compared with 71% of the untreated patients (p = 0.01). The CMV infections that did occur in IvIgG recipients developed significantly later than in untreated children (median time of onset after transplantation 2.60 vs. 1.35 months; p < 0.05) and generally were less severe, although 1 IvIgG recipient died despite prophylaxis. IvIgG administration did not affect the frequency of rejection or graft or patient survival. We conclude that IvIgG administration to high-risk pediatric renal transplant recipients may protect against posttransplantation CMV disease and may lessen the severity of infections that do develop in patients who receive it.

Effective immunization against influenza in pediatric renal transplant recipients.

Viral infections such as influenza are an important cause of morbidity following organ transplantation. We evaluated the immunogenicity of a commercially available influenza vaccine in pediatric renal transplant recipients in a two-phase, prospective study. In phase one, 47 transplant patients and seven control subjects with bronchopulmonary dysplasia received influenza vaccine. Sera were collected at the time of vaccination and 6 wk later. In phase two, sera from 18 transplant recipients and 47 healthy adults who had received the same vaccine were collected 6-12 months after vaccination. Antibody titers to the A/Taiwan/1/86 antigen were measured with hemagglutination inhibition assay in both phases of the study. Vaccine was well tolerated in all subjects. No vaccinated patient required hospitalization for complications of influenza infection. Vaccination did not increase the frequency of acute allograft rejection. In phase one, 43 patients (91%) and 5 controls (71%) either seroconverted (developed a fourfold or greater rise in titer), or developed post-vaccination titers > or = 1:160 (p = NS). Among the transplant recipients, non-seroconverters had a higher pre-vaccination geometric mean antibody titer (GMT) than those who seroconverted. Seroconversion developed independently of whether patients received double or triple immunosuppression. In phase two, post-vaccination GMT were similar for patients and control subjects at 11.5 and 8 months post-vaccination, respectively. In our study, influenza vaccination produced equivalent humoral immunity in transplant recipients and normal subjects. Routine influenza vaccination should be performed annually in this high-risk population.

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.

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.

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.

Relationships between functional assays and enzyme immunoassays as measurements of responses to acellular and whole-cell pertussis vaccines.

OBJECTIVE: To examine the relationships between functional assays and antigen-specific enzyme immunoassays in sera from a multicenter trial of 13 different experimental acellular pertussis vaccines and 2 licensed whole-cell vaccines, and to determine whether correlations previously observed among assays of specimens from pertussis patients and whole-cell vaccinees would apply to specimens from infants immunized with purified components in acellular vaccines. METHODS: Postimmunization sera were assayed for immunoglobulin G antibodies to pertussis toxin (PT), filamentous hemagglutinin, pertactin (PRN), and a mixture of types 2 and 3 fimbriae (FIM) by enzyme-linked immunosorbent assay, for whole-cell agglutinins (AGGs) and for PT-neutralizing antibodies by the Chinese hamster ovary (CHO) cell assay. Assay results were compared for individual sera, as well as for geometric mean antibody concentrations or titers (GMTs) calculated by vaccine or overall. RESULTS: For the 15 vaccines, the PT GMTs were highly correlated with the CHO assay GMTs (r = .92), and the FIM GMTs were highly correlated with the AGG GMTs (r = .96). For individual postvaccination sera, there was a significant correlation between the CHO titers and levels of antibody to PT whether the 15 vaccines were considered separately (.59 < or = r < or = .85) or combined (r = .81). For individual sera from infants immunized with the two whole-cell vaccines or any of the four acellular vaccines containing FIM, a strong correlation between AGG titer and FIM antibody was observed whether the vaccines were considered separately (.83 < or = r < or = .91) or together (r = .86). One vaccine without detectable FIM produced a measurable AGG response; for this vaccine, a moderate but significant correlation (R = .58) between PRN antibody and AGG titer was observed. CONCLUSION: These data indicate that appropriate antigen-specific enzyme-linked immunosorbent assays will furnish results similar to those provided by the CHO and AGG assays in the evaluation of the immunogenicity of component vaccines. Antibodies to FIM seem to include the most important AGGs; however, there is evidence that agglutination by PRN antibody may be detected in the absence of antibody to FIM.

Measles control in Kinshasa, Zaire improved with high coverage and use of medium titre Edmonston Zagreb vaccine at age 6 months.

BACKGROUND: To improve measles control in Kinshasa, Zaire, a project to increase vaccine coverage was begun in 1988, and in 1989, the city vaccination programme changed measles vaccination policy from Schwartz vaccine at age 9 months to medium titre Edmonston Zagreb (EZ) vaccine at age 6 months. We report the impact of the programme on measles incidence and mortality. METHODS: Data on vaccine coverage were obtained from cluster sample surveys conducted every 1-2 years and from routine reports of vaccine doses administered. Data on measles incidence and mortality were obtained from sentinel surveillance sites. The serological response to EZ measles vaccine was evaluated at a health centre in 1989 and in a community survey in 1990. RESULTS: Measles vaccine coverage estimated in cluster surveys increased from 50% of the 1984 birth cohort to 89% of the 1989 birth cohort, accepting either a home-based record or a verbal history of vaccination. Reported measles incidence per 10,000 [corrected] population decreased by over 90%, from 37.5 in 1980 (early vaccination years) to 1.6 in 1991. There was a relative decrease in the proportion of cases aged < 9 months (32% of cases in 1986-1987 and 23% of cases in 1990-1991) and an increase in the proportion aged > 23 months (29% of cases in 1986-1987 and 43% in 1990-1991). According to ELISA assays, 74-76% of children seroresponded to EZ vaccine administered at age 6-7 months under routine programme conditions. CONCLUSIONS: Measles can be controlled in urban areas, although it is difficult to determine how great a contribution vaccination at age 6 months makes over and above the achievement of high coverage.

Isotype and antigen specificity of pertussis agglutinins following whole-cell pertussis vaccination and infection with Bordetella pertussis.

Elevated agglutinin titers have been shown to correlate with protection from disease following whole-cell pertussis vaccination, but the isotype and antigen specificity of human agglutinating antibodies is unknown. In 13 immunoassays, immunoglobulin G antifimbria antibodies had the strongest correlation with agglutinin titers following culture-proven infection with Bordetella pertussis (R' = 0.79; P < 0.0001) and following whole-cell pertussis vaccination (R' = 0.87, P < 0.0001).

Response of human immunodeficiency virus-infected adults to measles-rubella vaccination.

Measles-mumps-rubella vaccine (MMR) is recommended for human immunodeficiency virus-infected (HIV+) adults. Data concerning MMR vaccination of HIV+ patients are limited to children. We evaluated 39 HIV+ (97% with > 200 CD4+ lymphocytes) and 17 non-HIV+ control adults receiving measles-rubella vaccine (MR). Clinical adverse events did not differ between groups. Prevaccination, three HIV+ and two control vaccinees were measles seronegative; no HIV+ and one control vaccinee seroconverted. No initially measles-seropositive vaccinee had a significant antibody elevation. Four HIV+ and three control vaccinees were rubella seronegative prevaccination; three HIV+ and two control vaccinees seroconverted. Among those initially rubella seropositive, two HIV+ and one control vaccinee had significant antibody elevations. There were no significant percentage CD4+ or CD8+ lymphocyte changes between groups. Three HIV+ vaccinees were p24 antigen positive pre- and postvaccination. Although MR vaccination appears safe in HIV+ adults, questions remain about the response of measles and rubella antibody-negative HIV+ adults and those with < 200 CD4+ lymphocytes.

Immunogenicity of high-titer Edmonston-Zagreb measles vaccine in human immunodeficiency virus-infected children in Kinshasa, Zaire.

The response to Edmonston-Zagreb vaccine (titer, 5.4 log10 pfu) was evaluated among children in a study of perinatal transmission of human immunodeficiency virus (HIV) in Kinshasa. Acute postvaccination adverse events were monitored for 49 HIV-infected and 376 non-HIV-infected infants, and measles antibody responses were assessed by ELISA for 34 HIV-infected and 255 non-HIV-infected infants. There was no increase in the incidence of common symptoms 7-10 days after vaccination. HIV-infected infants were more likely to have detectable prevaccination measles antibody, and seroconversion after vaccination was somewhat lower in HIV-infected (76.5%) than non-HIV-infected infants (85.5%). Seroconversion rates did not differ among children with or without rhinitis or fever at vaccination. High-titer Edmonston-Zagreb vaccine given at 6 months of age has the potential to provide earlier protection against measles; however, this vaccine is no longer recommended for routine use, and two doses of standard-titer vaccines remains the preferred option for measles vaccination of HIV-infected infants.

Safety and immunogenicity of bacille Calmette-Guérin, diphtheria-tetanus-pertussis, and oral polio vaccines in newborn children in Zaire infected with human immunodeficiency virus type 1.

OBJECTIVE: To determine the safety and immunogenicity of childhood vaccines in children with perinatally acquired human immunodeficiency virus type 1 (HIV-1) infection. DESIGN: Nonrandomized, prospective cohort study; 12-month follow-up period. SETTING: Obstetric wards and outpatient pediatric clinics at two large hospitals in Kinshasa, Zaire. PATIENTS: A total of 8108 pregnant women were screened for HIV-1 antibodies. The 474 children born to 466 seropositive women identified during screening and the 616 children born to 606 seronegative, age- and parity-matched women were vaccinated. INTERVENTION: The following vaccines were administered at the stated ages: bacille Calmette-Guérin (BCG) vaccine (2 days); trivalent oral Sabin poliomyelitis vaccine (2 days and 6, 10, and 14 weeks); and adsorbed diphtheria-tetanus-pertussis (DTP) vaccine (6, 10, and 14 weeks). MEASUREMENTS AND MAIN RESULTS: Protective antibody titers to tetanus and poliovirus types 1, 2, and 3 were achieved in 95% of all children. Among children with HIV-1 infection, 70.8% had protective antibody titers to diphtheria compared with 98.5% of uninfected children (p < 0.05). Geometric mean antibody titers to diphtheria and poliovirus types 1, 2, and 3 were significantly lower in children with HIV-1 infection than in uninfected children. Vaccine-associated side effects were similarly low in all children. CONCLUSIONS: The low incidence of side effects and the high proportion of children with HIV-1 infection who achieved protective postimmunization antibody titers support the continuing use of BCG, DTP, and oral polio vaccines in childhood immunization programs in HIV-1 endemic areas.