Response to influenza immunisation during treatment for cancer.

AIMS: To assess the annual risk of influenza infection in children with cancer and the immunogenicity of a trivalent split virus influenza vaccine in these children. METHODS: Eighty four children with cancer were tested for susceptibility to the circulating strains of influenza virus in autumn 1995 and 1996. Non-immunised children were reassessed the following spring for serological evidence of natural infection. Forty two patients received two doses of influenza vaccine. These children were receiving continuing chemotherapy for acute lymphoblastic leukaemia or were within six months of completing chemotherapy. RESULTS: Among the 84 children tested for influenza virus susceptibility only 8% of patients were fully protected (antibody titres >/= 40) against all three of the prevalent influenza virus strains; 33% were susceptible to all three viruses. Evidence of acquired natural infection was seen in 30% of unimmunised patients. Among immunised susceptible patients, 66% made some protective response to the vaccine and 55% showed protective antibody titres to all three viral strains following vaccination. Older age was associated with increased response to the H1N1 and H3N2 vaccine components, but total white cell count or neutrophil count at immunisation, type of cancer, or length of time on treatment for acute lymphoblastic leukaemia did not affect response. CONCLUSIONS: Most children with cancer studied were at risk of influenza infection. A significant response to immunisation was seen, supporting annual influenza vaccination for children being treated for cancer.     

Antibody Responses to Influenza Virus Vaccine in Patients With Acute Lymphocytic Leukaemia

Feery, B. J., Matthews, R. N., Evered, M. G., and Gallichio, H. A. (1979). Aust. Paediatr. J. , 15, 177–180. Antibody responses to influenza virus vaccine in children with acute lymphocytic leukaemia. Antibody responses to influenza immunization in children with acute lymphocytic leukaemia in remission were studied in two successive years. Initial antibody levels, the response to immunization, and final antibody levels were lower than in a group of children with cystic fibrosis. The results indicate that both primary and anamnestic antibody responses are depressed in children with acute leukaemia when they are on immunosuppressive therapy. Despite this depression the majority of the patients reached protective antibody levels to the A/Victoria/3/75 and A/Texas/1/77 (H3N2) antigens but not to the recent A/USSR/90/77 (H1N1) antigens.     

Immune response after influenza vaccination in children with cancer

PURPOSE: To assess the immune response to inactivated trivalent split influenza vaccine in children with cancer. PROCEDURES: Forty-four children with various types of malignancies received two doses of influenza vaccine 2-4 weeks apart. Hemagglutinin-inhibition (HI) antibody titers were determined in paired sera obtained just before the first vaccination and 4 weeks after the second vaccination. RESULTS: Influenza vaccine was administered to all children without any serious adverse effects. Protective titer rates (proportion of patients achieving antibody titers > or =40 among those with pre-vaccination titers <40) and response rates (proportion of patients with fourfold or more antibody rise) were 72% and 65% for H1N1, 60% and 40% for H3N2, and 38% and 46% for influenza B, respectively. However, patients on chemotherapy showed a significantly lower immune response to influenza A than those having completed chemotherapy; protection titer rates were 42% versus 90% for H1N1 (P = 0.006) and 25% versus 83% for H3N2 (P = 0.019). For influenza B, patients with low IgG showed a lower response rate than those with high IgG (29% vs. 61%, P = 0.040). Multivariate analysis revealed that factors significantly associated with a lower immune response were low IgG (P < 0.001) and administration of chemotherapy (P = 0.003) for H1N1, administration of chemotherapy (P = 0.008) for H3N2, and low white blood cell (WBC) count (P = 0.030) and low IgG (P = 0.030) for influenza B. CONCLUSIONS: Influenza vaccination given to children with cancer was safe and induced immune reaction comparable to healthy children, although patients on chemotherapy and/or with chemotherapy-related conditions had a limited ability to produce a sufficient immune response.     

Response to influenza immunisation during treatment for cancer

AIMS—To assess the annual risk of influenza infection in children with cancer and the immunogenicity of a trivalent split virus influenza vaccine in these children.METHODS—Eighty four children with cancer were tested for susceptibility to the circulating strains of influenza virus in autumn 1995and 1996. Non-immunised children were reassessed the following spring for serological evidence of natural infection. Forty two patients received two doses of influenza vaccine. These children were receiving continuing chemotherapy for acute lymphoblastic leukaemia or were within six months of completing chemotherapy.RESULTS—Among the 84 children tested for influenza virus susceptibility only 8% of patients were fully protected (antibody titres ? 40) against all three of the prevalent influenza virus strains; 33% were susceptible to all three viruses. Evidence of acquired natural infection was seen in 30% of unimmunised patients. Among immunised susceptible patients, 66% made some protective response to the vaccine and 55% showed protective antibody titres to all three viral strains following vaccination. Older age was associated with increased response to the H1N1 and H3N2 vaccine components, but total white cell count or neutrophil count at immunisation, type of cancer, or length of time on treatment for acute lymphoblastic leukaemia did not affect response.CONCLUSIONS—Most children with cancer studied were at risk of influenza infection. A significant response to immunisation was seen, supporting annual influenza vaccination for children being treated for cancer.     

Antibody responses after inactivated influenza vaccine in young children

BACKGROUND: The frequency and duration of antibody responses after trivalent inactivated influenza vaccine (TIV) in young children are not well defined and assume greater importance with the expanded recommendations for vaccine use in children aged 6 months-5 years. METHODS: Forty-three children aged 6-23 months were vaccinated with TIV in the fall of 2002. At enrollment the majority of children were seronegative to one or more of the vaccine antigens and had no previously documented influenza. Postvaccination sera were collected in the subsequent fall and winter seasons. Acute antibody responses to TIV were determined using standardized hemagglutination inhibition (HAI) and neutralization assays. In calculating the duration of responses, sequential sera were analyzed to the last available sera, to the point at which antibody became undetectable, or to intercurrent influenza infection. RESULTS: Forty-three subjects contributed 121 sera that were analyzed for HAI responses to TIV. Four-fold HAI rises after 2 doses of TIV in naive individuals were seen in 13 (72%) to H3N2, 22 (92%) to H1N1, and 15 (60%) to influenza B. Fewer 4-fold rises were seen in those with preexisting antibody. The results of microneutralization assays to H3N2 correlated well with HAI results. The time for antibody to decay to one-half of the postvaccination titer (t1/2) was approximately 126 days for H1N1 and 258 days for H3N2. CONCLUSIONS: Although not all children responded with 4-fold rises in antibody or achieved the putative protective titer of > or =1:32, the half-life of antibody suggested that children immunized in the fall should have immune responses sustained throughout the ensuing influenza season.     

Live attenuated and inactivated influenza vaccine in school-age children

In 1985, we enrolled 189 school-age children by family in a double-blind study to determine protection against influenza by a single dose of cold-recombinant bivalent A vaccine or commercial trivalent inactivated vaccine compared with placebo. All children in school or day care, 3 to 18 years of age, in an enrolled family received the same preparation. Following vaccination, 60% and 21% of cold-recombinant bivalent A vaccine recipients and 73% and 83% of trivalent inactivated vaccine recipients demonstrated fourfold or greater response in hemagglutination-inhibition antibody titer to A/H1N1 and A/H3N2, respectively. Sixty-seven percent of all trivalent inactivated vaccine recipients demonstrated a fourfold or greater serologic response to H1N1, H3N2, and influenza B following a single dose of vaccine. During the 1985-1986 influenza B/Ann Arbor epidemic, heterotypic protection afforded by the influenza B/USSR component of trivalent inactivated vaccine was 62% compared with placebo. A single dose of trivalent inactivated vaccine protected school-age children, 6 to 19 years of age, from influenza B infection; the rate of protection was 64% against infection and 73% against febrile illness.     

Assessment of the immune response to trivalent split influenza vaccine in children with solid tumors

PURPOSE: To assess the immune response to influenza vaccine in children with solid tumors receiving chemotherapy or under the influence of chemotherapy. METHODS: Forty-five children (aged 1-18) with solid tumors on chemotherapy or within 6 months of completion of chemotherapy were included in the study. The children received two doses of intramuscular trivalent split influenza vaccine with 1 month apart in November-December 2003 (children <4 age 0.25 ml; >4 age 0.5 ml). Antibody titer was detected in the pre-vaccination and 4-week post-vaccination sera by hemagglutination inhibition (HI) method. Immune responses were measured as protective, geometric mean titers (GMT), and fourfold rises in HI titers. RESULTS: We revealed that the post-vaccination GMT for each of the three antigens in patients with solid tumors has increased significantly (P < 0.05). A fourfold rise in the percentage of post-vaccination antibody titers has been detected as 84.4% for H(1)N(1), 77.8% for H(3)N(2), 60% for B. Stratification of patients as on active chemotherapy or being within 6 months of completion of chemotherapy in terms of fourfold rise in antibody titers exposed a statistically significant difference for only B (P = 0.34). Post-vaccination protective rates were between 86 and 97%. CONCLUSIONS: Due to the interruptions in treatment caused by influenza infections, and economic benefits of the vaccine, we suggest that inactivated influenza vaccine should be applied as two doses annually in patients with solid tumor.     

Immunization of HIV-infected children with varicella vaccine

OBJECTIVE: To determine the safety and immunogenicity of varicella vaccine in children with human immunodeficiency virus (HIV) infection. Children (n = 41) who were mildly affected by HIV (Centers for Disease Control and Prevention stage N1 or A1) and had no history or serum antibody indicative of prior varicella infection were immunized with two doses of live attenuated varicella vaccine. RESULTS: A minority of the vaccine recipients had mild local or systemic reactions. Vaccination had no effect on the clinical stage of HIV or the HIV RNA plasma load. CD4 cell percentage and CD4 cell count were marginally decreased at week 4 after the first vaccination; this effect was no longer present at week 8 after vaccination. Two months after the second dose of vaccine, 60% of vaccine recipients had anti-varicella antibody in their serum, and 83% had a positive lymphocyte proliferation assay response to varicella antigen. CONCLUSION: On the basis of its safety and immunogenicity, varicella vaccine should be considered in the childhood vaccines given to mildly affected HIV-infected children.     

Protective antibody responses to influenza A/H1N1/09 vaccination in children with celiac disease

Patients with celiac disease have an increased risk for severe influenza infection and they show less of a response to certain vaccine types. During the influenza A/H1N1/09 pandemic, we prospectively investigated pandemic vaccine responses in 14 pediatric patients with celiac disease and age-/sex-matched controls. All of the children with celiac disease reached protective antibody titers (≥40) and showed a geometric mean titer comparable with the control group (530 vs 573).     

Effect of yearly vaccinations with live,attenuated, cold-adapted,trivalent, intranasal influenza vaccines on antibody responses in children

BACKGROUND: The cold-adapted, trivalent influenza vaccine (CAIV-T) may become an option for annual vaccination. However, there is little information regarding the immune response to repeated immunization with CAIV-T. OBJECTIVE: To determine the antibody response to repeated immunization with CAIV-T and to compare this with the response after the first CAIV-T immunization. DESIGN AND METHODS: Healthy children were offered CAIV-T immunization for 4 consecutive years, and blood samples were taken from a subset in Years 1, 2 and 4. In Year 4, 156 similarly aged children who had not received influenza vaccine previously were immunized with the same CAIV-T. RESULTS: The H3N2 and B components of the CAIV-T induced high antibody titers in Year 1 that were maintained during 4 years. The H1N1 titers were lower than the H3N2 or B titers. Comparison of the group immunized for 4 consecutive years with the group immunized for the first time revealed the following: (1) before immunization yearly immunized subjects were more likely to be seropositive to each of the three vaccine strains than those immunized for the first time (P < 0.05 for each); (2) after immunization the percentage of seropositive subjects to each of the strains was similar; (3) after immunization titers were higher in the subjects immunized for the first time than those immunized yearly (P < 0.05 for H3N2 and B). CONCLUSION: Yearly vaccination with CAIV-T induced high antibody titers, especially to the H3N2 and B strains in the vaccines. The titers in those immunized with CAIV-T for the first time were higher than in those immunized for 4 consecutive years.     

Measuring antibody responses to a live attenuated influenza vaccine in children

BACKGROUND: Hemagglutination inhibition (HAI) assay is the standard method for evaluating inactivated influenza vaccines, but no standard assay has been established for evaluating live attenuated influenza vaccines (LAIV). LAIV containing A/Beijing/262/95(H1N1) induced low serum HAI antibody responses to the antigenic variant, A/New Caledonia/20/99(H1N1) in a serologic study but provided protection against the A/New Caledonia-like viruses in a community study. Neutralization and HAI assays were compared by measuring H1N1 cross-reactive antibody responses to the LAIV in children. METHODS: Sera were collected from 50 children 1-8 years of age before vaccination and 4-6 weeks after each dose of the LAIV. Antibody titers to the 3 vaccine viruses were measured by the HAI assay, whereas antibody titers against the H1N1 vaccine virus (A/Beijing/262/95) and 2 H1N1 antigenic variants (A/Shenzhen/227/95 and A/New Caledonia/20/99) were measured by the HAI and neutralization assays. RESULTS: Initially seronegative participants were more likely to develop HAI seroconversion responses to the 3 vaccine viruses than the baseline seropositive participants (77% versus 14% for H1N1, 100% versus 20% for H3N2, 100% versus 19% for B, P < 0.01, Fisher's exact test). For the H1N1 cross-reactive antibody responses, seroconversion rates measured by the neutralization assay were significantly higher than those measured by the HAI assay (95% versus 78%, P = 0.0485 for A/Beijing/262/95; 75% versus 24%, P < 0.0001 for A/Shenzhen/227/95; 51% versus 5%, P < 0.0001 for A/New Caledonia/20/99). CONCLUSIONS: The neutralization assay was more sensitive than the HAI assay for measuring H1N1 antibody responses after vaccination of children with the LAIV and may provide a better correlate of clinical protection provided by the LAIV.     

Diphtheria-tetanus-acellular pertussis and inactivated poliovirus vaccines given separately or combined for booster dosing at 4-6 years of age

BACKGROUND: In the United States, diphtheria-tetanus-acellular pertussis (DTaP) and inactivated poliovirus (IPV) booster vaccinations are recommended for children 4-6 years of age. A combined DTaP-IPV vaccine is being developed, which would reduce by one the number of injections in this age group. METHODS: Children 4-6 years of age were randomized (1:1:1:1) to receive booster vaccination with 1 of 3 combined DTaP-IPV lots plus the measles, mumps, and rubella vaccine (N = 3156 for pooled lots) or separate doses of DTaP + IPV + measles, mumps, and rubella vaccine (N = 1053). Immunogenicity was assessed in a subset of children (N = 1331). Safety (solicited and unsolicited symptoms) including detailed assessment of local swelling reactions, was assessed in all children. RESULTS: Increases in antibody geometric mean concentrations/titers 1 month after vaccination were observed for the diphtheria, tetanus, acellular pertussis, and polio antigens. At least 92.2% of combined DTaP-IPV subjects and 92.6% of separate DTaP + IPV subjects had a postvaccination booster response for one or more DTaP antigens. Booster responses to one or more poliovirus antigens were observed in at least 96.6% of combined DTaP-IPV subjects and 92.8% of separate DTaP + IPV subjects. The combined DTaP-IPV vaccine was noninferior to separately administered DTaP and IPV vaccines with respect to DTaP antigen booster response rates and poliovirus antibody geometric mean titers ratios. Reporting of solicited local and systemic events was comparable between both groups. CONCLUSIONS: The combination DTaP-IPV vaccine provided immunogenicity and reactogenicity that is comparable to separately administered DTaP and IPV vaccines, with the advantage of requiring one less injection.     

Trivalent, inactivated influenza virus vaccine in children with sickle cell disease

School-aged children with sickle cell disease who were administered a single dose of trivalent, inactivated influenza virus vaccine had serum antibody titers comparable to titers achieved in the two-dose trials carried out in 1978. The proportion exhibiting titers of 1:32 or greater ranged from 84% to 68% for the three antigens. Preschool children with sickle cell disease received two doses of the same vaccine four weeks apart and their postimmunization titers to each of the antigens were slightly lower. The vaccine, which contained 15 micrograms of hemagglutinin to each of three influenza viruses, A (H1N1), A (H3N2), and B, in a volume of 0.5 mL, was adequately immunogenic for schoolchildren who probably had been primed by previous natural infection. Younger children who received the same quantity in two divided doses four weeks apart had slightly lower but acceptable titers and tolerated the injections with few side reactions.     

Comparison of immunogenicity and tolerability of a virosome-adjuvanted and a split influenza vaccine in children

OBJECTIVE: To compare the immunogenicity and safety of a virosome-adjuvanted influenza vaccine (Inflexal V; Berna Biotech, Berne, Switzerland) and a split influenza vaccine (Fluarix; GlaxoSmithKline Biologicals, Rixensart, Belgium) in children. SUBJECTS AND METHODS: The subjects, 453 children ages 6 to 71 months, were stratified into primed and unprimed and age groups (6 to 35 and 36 to 71 months) and then randomized 1:1 to receive virosome-adjuvanted (n = 224) or split influenza vaccine (n = 229), a half or full dose was given intramuscularly according to age. Unprimed children received a second dose after 4 weeks. Blood samples (n = 326) collected pre-and 28 days postvaccination were analyzed by hemagglutination inhibition test. Safety assessments were made at baseline and follow-up visits by the investigators and by parents for the 4 days after vaccinations. RESULTS: Both vaccines induced an effective immune response. Seroconversion rates (>4-fold titer rise) against the WHO recommended strains A/New Caledonia (H3N2), A/Moscow (H1N1) and B/Hongkong (B) were 80.1, 66.0 and 90.4% for the virosome-adjuvanted and 75.9, 62.9 and 89.4% for the split influenza vaccine, respectively. Unprimed children's seroconversion rates for H3N2 were significantly higher (P = 0.02) for the virosome-adjuvanted (88.8%) than for split influenza vaccine (77.5%). Seroprotection rates (titer of > 40) for H3N2, H1N1 and B, respectively, were 87.8, 80.1 and 90.4% after vaccination with the virosome-adjuvanted vaccine and 82.9, 78.2 and 89.4% after the split influenza vaccine. Unprimed children's seroprotection rate was significantly higher (P = 0.03) for H3N2 after the virosome-adjuvanted (88.8%) than those for the split influenza vaccine (78.3%). Equivalent geometric mean titer fold increases were evident for both vaccines. No serious adverse events were seen. Pain/ tenderness, redness and swelling/induration was found in 25.4, 11.2 and 8.9% for the virosome-adjuvanted vaccine and in 24.0, 9.2 and 6.1% for the split influenza vaccine, respectively. The rates of fever, malaise/irritability and shivering was 6.3, 11.6 and 2.7% for the virosome-adjuvanted vaccine and 8.3, 11.8 and 2.6% for the split influenza vaccine, respectively. CONCLUSIONS: The virosome-adjuvanted influenza vaccine showed greater immunogenicity over the split influenza vaccine in unprimed children and showed a trend toward better immunogenicity in the rest of the study population. Both vaccines were well-tolerated.     

2009 H1N1 Influenza Pandemic

The 2009 H1N1 influenza pandemic took health care workers worldwide by surprise. Early in the course of the pandemic it was determined that children and pregnant women were at high risk of increased morbidity and mortality from the novel influenza virus. The Centers for Disease Control and Prevention and state and local public health officials quickly rallied to develop treatment guidelines for the new strain of influenza A, including emergency approvals for off-label use of some antiviral drugs. Prevention of the spread of influenza via vaccination and environmental controls is critical to the health of children. The 2009 H1N1 influenza virus emerged too late to be included in the 2009/2010 seasonal influenza vaccine, so production of a monovalent vaccine was set in motion. Five months from when the first cases of novel H1N1 appeared in Mexico and the United States, a vaccine was being distributed to high-risk patients. Looking ahead to the 2010/2011 influenza season, it is difficult to predict 2009 H1N1 activity. The 2010/2011 seasonal influenza vaccine will include the 2009 H1N1 strain, so it is critical to get all children vaccinated early in the flu season.     

Effect of fever on the serum antibody response of Gambian children to Haemophilus influenzae type b conjugate vaccine

BACKGROUND: Acute malaria is a major pediatric problem in developing countries and it is known to be immunosuppressive. METHODS: The serum antibody response to Haemophilus influenzae type b (Hib) conjugate vaccine was investigated in children ages 12 to 30 months with fever associated with malaria, fever associated with other causes or no fever. Groups of 57 children with malaria, 57 children with fever without malaria and 60 healthy children were bled and vaccinated with a single dose of H. influenzae type b capsular polysaccharide-tetanus protein conjugate vaccine. Of these 137 were bled again 1 to 2 months after vaccination. RESULTS: The median antibody titers at baseline were low and similar in the three groups; 77, 65 and 57% of children in the malaria, febrile and healthy groups, respectively, had prevaccination titers of anti-polyribosylribitol phosphate antibodies below 0.15 microg/ml. The median antibody titers after vaccination were 6.3, 7.5 and 23 microg/ml in the malaria, febrile and healthy groups, respectively (P < 0.001, healthy group vs. the two febrile groups). All the healthy children had protective titers (>0.15 microg/ml) after vaccination, but 11% of the children with malaria and 4% of the other febrile children did not have protective titers. CONCLUSIONS: Anti-polyribosylribitol phosphate titers after Hib vaccination were lower in children with malaria or other febrile illnesses at the time of vaccination than in controls. Fever associated with malaria or other acute illnesses is associated with a diminished response to Hib conjugate vaccine. These findings raise questions about the vaccination of febrile children and indicate the need for further studies in this area.     

Humoral and cellular immune responses in children given annual immunization with trivalent inactivated influenza vaccine

BACKGROUND: There have been no prior reports of the frequency of circulating influenza-specific, interferon gamma-producing memory CD4+ and CD8+ T-cells in healthy children who have received multiple influenza immunizations. METHODS: We evaluated 21 previously immunized children, ages 3 to 9 years, before and 1 month after administration of trivalent inactivated influenza vaccine. Frequencies of influenza-specific CD4+ and CD8+ T-cells stimulated with trivalent inactivated influenza vaccine or A/Panama (H3N2) virus were determined by flow cytometry, and antibody responses to vaccine strains and a drifted H3N2 strain were measured by hemagglutination inhibition assay and neutralizing antibody assays. RESULTS: Mean change in CD4+ and in CD8+ T-cell frequencies after immunization was 0.01% (P > 0.39) with postimmunization CD4+ frequencies higher than CD8+ frequencies. Children with more previous vaccinations had a higher baseline frequency of CD4+ T-cells (P = 0.0002) but a smaller increase or even a decline from baseline after immunization (P = 0.003). An association between age and change in frequency was not detected. Baseline geometric mean titers (GMTs) and seroprotection rates were significantly higher in older children against A/Panama (neutralizing baseline GMT, P = 0.0488) and A/New Caledonia (hemagglutination inhibition baseline GMT and seroprotection, P < 0.0297). Baseline GMTs against B/Hong Kong were not associated with age or quantity of prior vaccinations. CONCLUSIONS: These findings suggest that children may plateau in CD4+ T-cell responses to influenza antigens with repeated exposures and that the number of exposures may play a large role in building a memory CD4+ T-cell response to influenza A, perhaps independently from age.     

Assessment of parental report for 2009-2010 seasonal and monovalent H1N1 influenza vaccines among children in the emergency department or hospital

ObjectiveTo assess the validity of parental report for seasonal and monovalent H1N1 influenza vaccinations among children 6 months to <18 years who were recommended to receive both vaccines in 2009–2010.MethodsChildren with fever or respiratory symptoms were prospectively enrolled in both emergency departments in Forsyth County, North Carolina, and the only pediatric hospital in the region. Enrollment occurred from September 1, 2009, through April 12, 2010, during the H1N1 influenza pandemic. A parental questionnaire was administered by trained interviewers to ascertain the status of seasonal and monovalent H1N1 influenza vaccines. Parental report was compared with that documented in the medical record and/or the North Carolina immunization registry.ResultsAmong 297 enrolled children 6 months to <18 years of age, 174 (59%) were 6 months to 4 years, 67 (23%) were 5–8 years, and 56 (19%) were 9 to <18 years. Parents reported that 140 (47%) children had received ≥1 dose of 2009–2010 influenza vaccine—128 (43%) for seasonal vaccine and 63 (21%) for H1N1 vaccine. Confirmed vaccination data indicated that 156 (53%) children had received ≥1 dose of any 2009–2010 vaccine—120 (40%) for seasonal vaccine and 53 (18%) for H1N1 vaccine. Parental report of any seasonal influenza vaccination was 92% sensitive and 86% specific and had a kappa of 0.76. Parental report for any H1N1 influenza vaccination was 88% sensitive and 92% specific with a kappa of 0.71.ConclusionsParental report of 2009–2010 seasonal and monovalent H1N1 influenza vaccinations was sensitive and specific and had reasonable agreement with the medical record and/or immunization registry.     

Safety and immunogenicity of three doses of a five-valent pneumococcal conjugate vaccine in children younger than two years with and without human immunodeficiency virus infection

OBJECTIVE: To assess the safety and immunogenicity of three doses of a five-valent (types 6B, 23F, 14, 18C, and 19F) pneumococcal conjugate vaccine (PCV) among children younger than 2 years who are and are not infected with human immunodeficiency virus (HIV). METHODS: A convenience sample of 18 HIV-infected children 2 years and younger (mean, 12.9 months) received three doses (each separated by 2 months) of PCV. An additional convenience sample of 33 non-HIV-infected children of virtually identical age, race, and sex as the HIV-infected group were randomized in a double-blind fashion to receive three doses of PCV or saline placebo. Safety data were collected for 72 hours after each vaccination. Sera were obtained before each and 1 month after the third vaccination to determine vaccine type-specific immunoglobulin G pneumococcal antibody titers by an enzyme-linked immunosorbent assay. RESULTS: Seventeen HIV- and 30 non-HIV-infected children completed the study. The PCV was well tolerated by both HIV- and non-HIV-infected children. No significant differences in local or systemic reactions were noted between HIV- and non-HIV-infected PCV or placebo recipients. Three doses of PCV were immunogenic, as evidenced by 16- to 659-fold increases in type-specific geometric mean antibody titers over prevaccination levels in HIV- and non-HIV-infected children. With respect to an arbitrary protective level, 78% of the antibody titers from HIV-infected children and 88% of the titers from non-HIV-infected children were 1.0 microgram/mL or greater 1 month after the third PCV dose. HIV-infected children with milder disease (Centers for Disease Control and Prevention classes N1-2, A1-2, and B1) were more likely to have protective antibody titers after the first and second PCV doses than HIV-infected children with more advanced disease (Centers for Disease Control and Prevention classes N3, A3, B2-3, and C1-3). However, after the third PCV dose, these differences disappeared. CONCLUSION: Three doses of PCV seem safe and immunogenic in both HIV- and non-HIV-infected children younger than 2 years. This type of vaccine should result in a marked reduction in systemic pneumococcal disease in both HIV- and non-HIV-infected children. Given the high incidence of invasive pneumococcal disease in HIV-infected children, this vaccine may markedly improve the quality of life for this unfortunate group of children.     

Rubella immunization in human immunodeficiency virus type 1-infected children: cause for concern in vaccination strategies

BACKGROUND: HIV infection can have important although sometimes unexpected consequences, such as contributing to enlargement of the pool of rubella-susceptible children. METHODS: At the Federal University of S?o Paulo, Brazil, we assessed response to rubella immunization at 15 months of age in 15 human immunodeficiency virus type 1 (HIV)-infected children, 20 seroreverted children (SR) and 18 healthy control children born to HIV-seronegative mothers (CON). Blood samples were collected before and 3 months after vaccination. All HIV-infected children had started highly active antiretroviral therapy during their first 6 months of life. Serum samples were tested with a rubella IgG enzyme-linked immunosorbent assay kit. RESULTS: HIV children in immunologic categories 2/3 had lower rubella antibody titers (geometric mean, 33 IU/mL) than those from CON (125 IU/mL) and SR group (236 IU/mL) (Tukey, P = 0.01). Antibody values after vaccination were positively associated with CD4 T cell numbers and negatively associated with HIV viral load assessed immediately before vaccination. The percentage of children with protective antibodies after vaccination (above 10.0 IU/mL) was also significantly different among groups (Fisher's exact test, P = 0.013): CON, 94%; SR, 100%; HIV category 1, 100%; HIV category 2/3, 62%. CONCLUSIONS: HIV-infected children with a preserved immune system at measles-mumps-rubella immunization can have a good response to rubella vaccine. In contrast, those in more advanced categories for HIV infection respond poorly.