A comparative study of the serological response to Japanese encephalitis vaccine in HIV-infected and uninfected Thai children

We report a prospective study of mouse brain derived inactivated Japanese encephalitis (JE) vaccine, given in 3-dose EPI program to human immune deficiency virus (HIV)-exposed Thai infants. 18 HIV-infected receiving antiretroviral therapy with median baseline CD4 of 33.1%, and 92 HIV-uninfected children were studied. All but one HIV-infected child seroconverted after the second dose. The geometric mean titers (GMTs) 3 months after the second and third doses in HIV-infected vs HIV-uninfected children were 247 vs 938 (p = 0.022), and 2273 vs 24069 (p = 0.009), respectively. Urticaria or angioedema found in 4% and 6% in HIV-infected and -uninfected children, respectively (p = 1.0). The vaccine was safe and immunogenic but antibody response in HIV-infected children was not as high as in uninfected children.     

Immune response to tetanus booster in infants aged 15 months born prematurely with very low birth weight

Objectives

To compare humoral and cellular immune responses to tetanus booster vaccination in infants born prematurely with those born at full term and identify factors associated with the humoral response.

Methods

A prospective study was carried out on children born prematurely and with a birth weight <1500 g and with infants born at full term. At 15 months (pre-vaccination) and 18 months (post-vaccination), anti-tetanus antibodies were measured by ELISA; the intracellular interferon-gamma percentages of CD4+ T and CD8+ T cells after in vitro stimulation with tetanus toxoid were determined by flow cytometry. Chi-squared or Fisher's exact test was used to compare categorical variables. Student's t-test or Mann–Whitney test was used to compare numerical variables. Regression analysis was performed to determine factors associated with humoral immunity. Statistical significance was considered if p < 0.05.

Results

Sixty-four premature and 54 full-term infants were studied. The proportion of children immune against tetanus at 15 and 18 months was similar in both groups. The geometric mean of the antibodies was lower among the premature children at 15 months (p = 0.025) and was similar in both groups at 18 months (p = 0.852). The percentages of CD4+ and CD8+ T cells expressing intracellular IFN-γ were similar in both groups at 15 and 18 months. Gestational age <32 weeks was associated with a reduction of −0.116 IU/mL in the level of antibodies at 15 months. Breastfeeding >6 months was associated with a 3.5-fold greater chance of optimal protective (≥0.1 IU/mL) antibody level against tetanus at 15 months and an increase of 0.956 IU/mL in the level of antibodies at 18 months.

Conclusions

Humoral and cellular response following a tetanus booster was similar in both groups. Premature infants exhibited lower levels of anti-tetanus antibodies at 15 months of age, with the lowest levels in those born at a gestational age of less than 32 weeks. Breastfeeding was associated with greater levels of antibody against tetanus.     

The immunogenicity and safety of pneumococcal conjugate vaccine in human immunodeficiency virus-infected Thai children

Background

HIV-infected children have high risk of invasive pneumococcal disease (IPD) despite receiving highly active antiretroviral therapy (HAART). This study aimed to determine the immunogenicity and safety of a 7-valent pneumococcal conjugate vaccine (PCV-7) in Thai HIV-infected children compared to HIV-exposed uninfected children.

Methods

A prospective study was conducted among children 2 months to 9 years. The number of PCV-7 doses depended upon age and HIV status; 2-6 months of age: 3 doses; 7-23 months of age: 2 doses; HIV-infected child ≥24 months: 2 doses and HIV-exposed child ≥24 months: 1 dose. Serotype-specific pneumococcal IgG antibody concentrations were measured at baseline and 28 days after complete vaccination. The primary end point was the proportion of children who achieved serotype-specific IgG antibody concentration at a cut off level ≥0.35 μg/mL. Secondary end points were a 4-fold increase in serotype-specific IgG antibody, rates of adverse events and predictors for seroconversion among HIV-infected children.

Results

Fifty-nine HIV-infected and 30 HIV-exposed children were enrolled. The median (IQR) age was 97 (67-111) and 61 months (51-73), respectively (p < 0.001). Among HIV-infected children, current and nadir CD4 counts were 1079 cell/mm³ and 461 cell/mm³, respectively. The proportion of children who achieved pneumococcal IgG ≥0.35 μg/mL was in the range of 85-98% in HIV-infected and 83-100% in HIV-exposed children depending on serotype. The lowest response was to serotype 6B in both groups. The 4-fold increase in serotype-specific IgG concentrations was similar between HIV-infected and HIV-exposed groups, except for serotype 9V (p = 0.027). HIV-infected children who had a history of AIDS had a lower antibody response to serotype 23F (p = 0.025). Seven (12%) HIV-infected children had a grade 3 local reaction.

Conclusion

PCV-7 is highly immunogenic and safe among HIV-infected children treated with HAART. The use of the pneumococcal conjugate vaccine among HIV-infected children is encouraged in order to prevent IPD.     

Prevalence of protective level of hepatitis B antibody 3 years after revaccination in HIV-infected children on antiretroviral therapy

After responding to highly active antiretroviral therapy (HAART), HIV-infected children had a good response to hepatitis B immunization. However, there are limited data on the durability of antibody to hepatitis B surface antigen (anti-HBs) in these children. The primary objective of this study is to determine the prevalence of protective anti-HBs level 3 years after a 3-dose HBV revaccination among HIV-infected children with immune recovery (CD4 cell ≥15%) while on HAART. The secondary objective is to assess immunologic memory among children who had waning of anti-HBs. An anti-HBs level of ≥10 mIU/mL was defined as a protective antibody level. Sixty-nine HIV-infected children who had history of a 3-dose HBV revaccination while receiving HAART were enrolled. The mean (SD) of CD4 cell and duration of HAART at time of revaccination was 27.2% (6.7) and 5.9 years (0.4), respectively. The proportion of children with protective anti-HBs level 3 years after the revaccination was 71.0% [95% CI, 58.8-81.3]. The geometric mean titer was 114(SD 5) IU/mL. By multivariate logistic analysis, the predictors for protective anti-HBs level 3 years after revaccination were CD4 cell count ≥500 cells/mm³ at the time of vaccination (p = 0.04) and anti-HBs level ≥ 100 IU/mL at 1 month after completion of the 3-dose vaccination (p < 0.001). Anamnestic response after one booster dose was demonstrated among 14 of 17 children who had waning protective anti-HBs level (82.4% [95% CI, 62.2-102.6]). Our findings support the recommendation of giving a 3-dose HBV vaccination to HIV-infected children with immune recovery while receiving HAART.     

Immune response to a Tdap booster in vertically HIV-infected adolescents

BackgroundPertussis cases have increased worldwide and knowledge on immune response and cytokine profile after Tdap vaccine in immunodeficient adolescents is scarce.ObjectiveTo evaluate the immune response after Tdap in HIV-infected (HIV) and in healthy adolescents (CONTROL).MethodologyThirty HIV adolescents with CD4 cell counts >200 and 30 CONTROLs were immunized with Tdap, after a prior whole-cell DTP vaccine primary scheme. Blood samples were collected immediately before and after vaccine. Lymphocyte immunophenotyping was performed by flow cytometry; tetanus, diphtheria and pertussis toxin antibodies were assessed by ELISA; whole blood was stimulated with tetanus toxoid and Bordetella pertussis and supernatants were assessed for cytokines by xMAP.ResultsMean age of HIV and CONTROL groups were 17.9 e 17.1 years, respectively. Pain at injection site was more intense in CONTROL group. HIV group had similar increase in tetanus antibodies at 28 days (geometric mean concentration, GMC, 15.6; 95% CI, 7.52–32.4) than CONTROL group (GMC, 23.1; 95% CI, 15.0–35.5), but lower diphtheria antibodies at 28 days (GMC, 2.3; 95% CI, 0.88–6.19) than CONTROL group (GMC, 16.4; 95% CI, 10.3–26.2); for pertussis, the percentage of individuals who seroconverted was lower in HIV than CONTROL group (HIV, 62.1% versus CONTROL, 100%; p = .002). Both groups built a cellular immune response to tetanus, with a Th2 (IL-4, IL-5 and IL-13) and Th1 (IFN-γ) response, with lower cytokine levels in HIV than in CONTROL group. Especially for pertussis, cellular and humoral responses were less intense in HIV adolescents, with a lower Th1 and Th17 profile and higher IL-10 levels. HIV-infected adolescents on viral suppression showed an enhanced immune response to all the three vaccine antigens, although still at lower levels if compared to CONTROL group.ConclusionsBoth groups tolerated well and built an immune response after Tdap. However, HIV-infected adolescents would probably benefit from more frequent booster doses.     

Chemotypical variations in Withania somnifera lead to differentially modulated immune response in BALB/c mice

Withania somnifera (Ashwagandha) is a plant with known ethnomedicinal properties and its use in Ayurvedic medicine in India is well documented. The present investigation reports on immunomodulatory efficacy of aqueous-ethanol extracts of roots of three selected Withania somnifera chemotypes designated as NMITLI 101R, NMITLI 118R and NMITLI 128R. Each chemotype was administered 10-100 mg/kg orally to BALB/c mice once daily for 14 days. The immunomodulatory consequences were recorded by determining the humoral immune response with the help of hemagglutination, plaque forming cell assay and cellular response by measuring delayed type hypersensitivity reaction. Additionally, other immune parameters such as proliferation of T and B cells, intracellular and secreted Th1 and Th2 cytokines along with modulation in ROS production by peritoneal macrophages were monitored after feeding with lower doses (3-30 mg/kg/day) of these three chemotypes individually. NMITLI 101R incited both humoral and cellular immune response in terms of higher number of antibody producing cells and enhanced foot pad swelling at the 10 mg dose as also dose dependent B and T cell proliferations. Levels of intracellular and secreted cytokines post-NMITLI 101R treatment illustrated generation of mixed Th1/Th2 response that remained more polarized towards Th1. This chemotype also generated maximum reactive oxygen species. NMITLI 118R provoked comparatively reduced immune response in all humoral and cellular parameters at lower doses but induced highly polarized Th1 cytokine response. In contrast, NMITLI 128R led to enhanced antibody production with minimal cellular response demonstrating marginally Th2 dominance at a lower dose. Taken together, it may therefore be concluded that there were distinct modulation in the immune response exhibited by the three chemotypes of Withania somnifera and NMITLI 101R appeared to possess a better immunostimulatory activity than the other chemotypes at lower doses.     

Safety and immunogenicity of single dose of tetanus–diphtheria (Td) vaccine among non/partially immune children against diphtheria and/or tetanus,Hyderabad, India, 2007

In Hyderabad, India, diphtheria is common among children aged 5–19 years. On account of low coverage of diphtheria vaccine boosters recommended under the universal immunization programme, a large proportion of children were susceptible/partially immune against diphtheria and/or tetanus. We evaluated immunogenicity and safety of single dose of indigenously developed tetanus–diphtheria (Td) vaccine (diphtheria–toxoid ≤5 Lf) among 483 school children from Hyderabad aged 7–17 years and susceptible/partially immune against diphtheria and/or tetanus. Serological testing 6 weeks after vaccination indicated that vaccine was highly immunogenic with >96% sero-protected against both antigens. The immune response observed indicated a booster response to previously acquired immunity. Administration of additional dose of Td vaccine to the older school children and replacing the tetanus toxoid vaccine with Td in the school health programme would considerably reduce diphtheria burden in Hyderabad.     

Humoral responses to independent vaccinations are correlated in healthy boosted adults

Background

Roughly half of U.S. adults do not receive recommended booster vaccinations, but protective antibody levels are rarely measured in adults. Demographic factors, vaccination history, and responses to other vaccinations could help identify at-risk individuals. We sought to characterize rates of seroconversion and determine associations of humoral responses to multiple vaccinations in healthy adults.

Methods

Humoral responses toward measles, mumps, tetanus toxoid, pertussis, hepatitis B surface antigen, and anthrax protective antigen were measured by ELISA in post-immunization samples from 1465 healthy U.S. military members. We examined the effects of demographic and clinical factors on immunization responses, as well as assessed correlations between vaccination responses.

Results

Subsets of boosted adults did not have seroprotective levels of antibodies toward measles (10.4%), mumps (9.4%), pertussis (4.7%), hepatitis B (8.6%) or protective antigen (14.4%) detected. Half-lives of antibody responses were generally long (>30 years). Measles and mumps antibody levels were correlated (r = 0.31, p < 0.001), but not associated with select demographic features or vaccination history. Measles and mumps antibody levels also correlated with tetanus antibody response (r = 0.11, p < 0.001).

Conclusions

Vaccination responses are predominantly robust and vaccine specific. However, a small but significant portion of the vaccinated adult population may not have quantitative seroprotective antibody to common vaccine-preventable infections.     

Different T cell memory in preadolescents after whole-cell or acellular pertussis vaccination

To better understand vaccine-induced protection and its potential failure in light of recent whooping cough resurgence, we evaluated quantity as well as quality of memory T cell responses in B. pertussis-vaccinated preadolescent children. Using a technique based on flow cytometry to detect proliferation, cytokine production and phenotype of antigen-specific cells, we evaluated residual T cell memory in a cohort of preadolescents who received a whole-cell pertussis (wP; n = 11) or an acellular pertussis vaccine (aP; n = 13) during infancy, and with a median of 4 years elapsed from the last pertussis booster vaccine, which was aP for all children. We demonstrated that B. pertussis-specific memory T cells are detectable in the majority of preadolescent children several years after vaccination. CD4⁺ and CD8⁺ T cell proliferation in response to pertussis toxin and/or filamentous hemagglutinin was detected in 79% and 60% of the children respectively, and interferon-γ or tumor necrosis factor-α producing CD4⁺ T cells were detected in 65% and 53% of the children respectively. Phenotyping of the responding cells showed that the majority of antigen-specific cells, whether defined by proliferation or cytokine production, were CD45RA⁻CCR7⁻ effector memory T cells. Although the time since the last booster vaccine was significantly longer for wP-compared to aP-vaccinated children, their proliferation capacity in response to antigenic stimulation was comparable, and more children had a detectable cytokine response after wP- compared to aP-vaccination. This study supports at the immunological level recent epidemiological studies indicating that infant vaccination with wP induces longer lasting immunity than vaccination with aP-vaccines.     

The relationship between concentration of specific antibody at birth and subsequent response to primary immunization

Background and aims

Trans-placentally acquired antibodies can protect infants from infection in the first months of life. However, high concentrations of antibody at birth may impact the infant's own immune response to primary immunization. We examine the relationship between concentration of specific antibody to Bordetella pertussis, Haemophilus influenzae type b (Hib), tetanus toxoid and pneumococcal antigens at birth and following primary immunization.

Methods

Healthy mother–infant pairs were recruited from a UK maternity unit. Peripheral blood samples were obtained at birth and 4 weeks after primary immunization. Specific antibody concentrations were determined using enzyme-linked immunosorbent assays. Pertussis antibody concentrations >50 IU/ml, Tetanus antibody levels >0.1 IU/ml and Hib antibody levels >0.15 mg/l were regarded as protective.

Results

Following primary immunization, 35/36 (97%) infants had specific antibody concentrations associated with protection against Hib, 32/36 (89%) against pertussis and 36/36 (100%) against tetanus. Concentrations of all specific antibodies were significantly higher than at birth (p < 0.0001), except anti-tetanus toxoid, p = 0.41. However, there was an inverse correlation between infant antibody concentration at birth and fold-increase in antibody concentration post-immunization for tetanus: r_s −0.86 (95%CI −0.93 to −0.74), p < 0.0001; pneumococcus: r_s −0.82 (95% CI −0.91 to −0.67), p < 0.0001; pertussis: r_s −0.77 (95% CI −0.89 to −0.58), p < 0.0001 and Hib: r_s −0.66 (95%CI −0.82 to −0.42), p < 0.0001. The highest concentrations of specific IgG at birth were associated with lower concentrations post-immunization for tetanus (p = 0.009) and pneumococcus (p = 0.03). This association was not observed for Hib (p = 0.88) or pertussis (p = 0.14).

Conclusion

Higher antibody concentration at birth appeared to inhibit the response to infant immunization for tetanus and pneumococcus; the effect was less marked for Hib and pertussis. However, the majority of infants achieved high antibody levels post-immunization. This supports maternal immunization, as high levels of maternally derived antibody at birth may not inhibit infants’ immunization responses in a clinically relevant manner.     

Evaluation of immune responses to combined hepatitis A and B vaccine in HIV-infected children and children on immunosuppressive medication

Objective

A phase IV interventional study with a combined hepatitis A and B vaccine was conducted in HIV-infected children and children receiving immunosuppressive medication for treatment of rheumatic diseases to evaluate immune responses.

Methods

Both groups (1–16 years of age) received combined (inactivated) HAV and (rDNA) HBV vaccine Ambirix^® at months 0 and 6. Serum samples were taken at four time points and tested for anti-HAV and anti-HBs antibodies. Anti-HAV concentrations ≥20 mIU/mL or anti-HBs concentrations ≥10 mIU/mL were considered protective. Seropositivity percentages were calculated and geometric mean concentrations (GMCs) were compared by nonparametric Mann–Whitney U-test or Kruskal–Wallis one-way-analysis-of-variance.

Results

Of 80 HIV-infected children who completed the study, 67 were HAV-susceptible and 68 HBV-susceptible at enrolment. Of 80 children with rheumatic diseases who completed the study, 65 were HAV-susceptible and 74 HBV-susceptible at enrolment. Immune responses to HAV after first dose of vaccine in both study groups were low: 71% and 55% respectively, whereas immune responses after the second dose were 99% and 100% respectively. Immune response to HBV after first dose of vaccine in both groups was also low: 27% and 17% respectively. Immune responses after the second dose were 97% and 93%, respectively. A larger proportion of children on combination antiretroviral therapy (cART) and of children with viral load <50 copies/mL responded to HBV, and also showed a significantly higher GMC.

Conclusions

Although immune response after full series of combined HAV and HBV vaccine in both groups was excellent and comparable to healthy children, a substantial proportion of both groups was not protected for HAV after first dose of vaccine. This protection gap is especially important for HAV in travel health and postexposure prophylactic treatment: both groups of children should be serologically tested for anti-HAV prior to travel to ensure protection if there is no time to await second dose of vaccine.     

A mixture of three prebiotics does not affect vaccine specific antibody responses in healthy term infants in the first year of life

Background

Previous studies have shown, that prebiotics can modulate the immune response in infants at risk for allergy, leading to a lower incidence of atopic dermatitis. Few studies have evaluated the effect of prebiotic carbohydrates alone on the vaccine-specific antibody response as a marker for the development of the immune system in healthy infants not at risk for allergy.

Aim

This study evaluates the effect of adding a specific prebiotic mixture of short chain galacto-oligosaccharides (scGOS)/long chain fructo-oligosaccharides (lcFOS) ratio 9:1 and pectin-derived acidic oligosaccharides (pAOS) to formula feeding on the specific immunoglobulin responses to Haemophilus influenza type b (Hib) and tetanus immunization in healthy non-atopic infants during the first year of life.

Methods

This substudy has been embedded in a multinational multicenter RCT (n = 1130 children) to evaluate the effect of study prebiotics on the incidence of fever episodes during the first year of life. The study prebiotics were administered throughout the first year of life. This is a substudy on the vaccine-specific immunoglobulin responses to Hib and tetanus immunizations. Only data of the Dutch children, 80 in the prebiotics group and 84 in the control group, were used for this substudy. They all followed the national vaccination schedule leading to a homogeneous group. Blood was sampled at 6 and 12 months of age.

Results

Hib immunizations: median values did not differ between groups at the age of 6 and 12 months. At the age of 12 months, 34 out of 37 (91.9%) infants in the prebiotics group and 31 out of 34 infants (91.2%) in the control group had Hib antibody levels >1.0 μg/ml.Tetanus immunizations: median values did not differ between groups at the age of 6 and 12 months and were above the cut-off value of 0.1 IU/ml in all infants in both the prebiotics and the control group.

Conclusion

No effect of prebiotics supplementation on vaccination specific antibody levels was found in children up to the age of 12 months; the vaccine specific antibody levels in infants fed the study prebiotics or a control diet were similar during the first year of life. We hypothesize that this specific prebiotic mixture, which resembles the composition of oligosaccharides in human milk, mainly promotes Th1 and Treg dependent immune responses and induces a down regulation of IgE-mediated allergic responses, while the desired vaccine-specific serum antibody responses remain intact.     

Mother-infant vaccination with pneumococcal polysaccharide vaccine: persistence of maternal antibodies and responses of infants to vaccination

Protection against pneumococcal infection early in life is needed. This could be achieved by maternal vaccination or by starting infant vaccinations as early as possible. In an open controlled study, pregnant women received both 23-valent pneumococcal polysaccharide vaccine (PPV), Haemophilus influenzae type b conjugate vaccine and tetanus toxoid or tetanus toxoid alone. Infants received PPV at 7 or 17 weeks and the second dose at 3 years of age. Antibodies to six pneumococcal serotypes were measured with the non-22F and 22F enzyme immunoassays (EIA). Elevated antibody concentrations after maternal vaccination persisted in infants until 4 months of age. Infants responded to serotypes 1 and 5, but not to serotypes 6B, 14, 18C and 19F. High maternal antibody concentrations at early age reduced the responses, but not the antibody concentrations, of infants to PPV. The percentages of infants with concentrations >0.35 μg/ml and >1 μg/ml were high at birth, but decreased by age during the first 10 months of life. Revaccination with PPV at 3 years of age induced a good immune response.     

Protective effect against toxoplasmosis in mice induced by DNA immunization with gene encoding Toxoplasma gondii ROP18

Toxoplasma gondii is an obligate intracellular protozoan parasite infecting mammals and birds including humans. Rhoptry protein 18 has been implicated as an important virulence factor. In this study, we constructed a DNA vaccine expressing rhoptry protein 18 (ROP18) of T. gondii, and evaluated the immune response and protective immunity in Kunming mice. The gene sequence encoding ROP18 was inserted into the eukaryotic expression vector pVAX I. Intramuscular immunization of mice with pVAX-ROP18 elicited specific humoral responses and stimulated lymphoproliferation (P < 0.05). The cellular immune response was associated with the production of IFN-γ, indicating that a Th1 type response was elicited, which was confirmed by the production of large amounts of IgG2a (P < 0.05). By the expression of the CD69, an activation marker of CD4+ and CD8+ T cells, we found that pVAX-ROP18 enhanced the activation of CD4+ and CD8+ T cells in lymphoid in mice. After lethal challenge, the mice immunized with the pVAX-ROP18 showed a significantly increased survival time (27.9 ± 15.1 days) compared with control mice which died within 7 days of challenge (P < 0.05). Our results show for the first time, that a ROP18 vaccine construct can enhance the T. gondii-specific CTL. Th1 responses and increased survival suggested that ROP18 is a promising vaccine candidate against infection with T. gondii.     

Immunogenicity and reactogenicity of co-administered tetanus-diphtheria-acellular pertussis (Tdap) and tetravalent meningococcal conjugate (MCV4) vaccines compared to their separate administration

In the United States, co-administration of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine and tetravalent meningococcal conjugate vaccine (MCV4) is recommended in adolescents. In this clinical study, 1341 adolescents received Tdap (Boostrix® GlaxoSmithKline) and MCV4 (Menactra®, Sanofi-Pasteur) simultaneously or sequentially one month apart. Co-administration of Tdap + MCV4 was well tolerated and immunogenic, resulting in high levels of antibodies against diphtheria, tetanus, pertussis and meningococcal serogroup A,C,W-135 and Y antigens. The data provide support for current recommendations for co-administration of Tdap and MCV4 vaccines at the same office visit.     

Positive association between dietary iron intake and iron status in HIV-infected children in Johannesburg,South Africa

Anemia is a common complication of pediatric HIV infection and is associated with suboptimal cognitive performance and growth failure. Routine iron supplementation is not provided to South African HIV-infected children. We hypothesized that dietary iron intake without supplementation is sufficient to protect against iron deficiency (ID) in HIV-infected children receiving highly active antiretroviral therapy. In this prospective study, the difference between dietary intakes of iron-deficient children (soluble transferrin receptor >9.4 mg/L) and iron-sufficient children after 18 months on highly active antiretroviral therapy was examined. The association between iron intake and hemoglobin (Hb) concentration was also assessed. Longitudinal data collected for 18 months from 58 HIV-infected African children were assessed by generalized estimation equations, with adjustment for demographic information, dietary intakes, growth parameters, and CD4%. After adjustment for covariates, the longitudinal association between dietary iron intake and Hb concentration remained significant. This association shows that for every 1-mg increase in iron intake per day, Hb increases by 1.1 g/L (P < .001). Mean Hb increased significantly after 18 months of follow-up (106 ± 14 to 129 ± 14 g/L, P < .01), but soluble transferrin receptor also increased (7.7 ± 2.7 to 8.9 ± 3.0 mg/L, P < .01). The incidence of ID increased from 15.2% at baseline to 37.2% after 18 months. Children with animal protein intakes greater than >20 g/d had significantly lower odds for ID at 18 months than did children with lower intakes (odds ratio, 0.40; 95% confidence interval, 0.21-0.77). Dietary iron intake was insufficient to protect against ID, pointing to a need for low-dose iron supplementation for iron-deficient HIV-infected children and interventions to increase the consumption of animal protein.     

Serum antibody response to three non-typeable Haemophilus influenzae outer membrane proteins during acute otitis media and nasopharyngeal colonization in otitis prone and non-otitis prone children

Non-typeable Haemophilus influenzae (NTHi) is the most common bacteria responsible for episodic acute otitis media (AOM; non-otitis prone), recurrent AOM (rAOM; otitis prone) and AOM treatment failure (AOMTF) in children. In this 3.5 years of prospective study, we measured the serum antibody response to outer membrane proteins D, P6 and OMP26 of NTHi in children with AOM (n = 26), rAOM (n = 32), AOMTF (n = 27). The geometric mean titers (GMTs) of IgG at their acute AOM visit against Protein D in otitis prone children were significantly lower compared to AOMTF (p value < 0.01) and non-otitis prone (p value < 0.03) children; otitis prone children had significantly lower IgG levels to P6 compared to AOMTF children (p value < 0.02); otitis prone children had significantly lower IgG levels to OMP26 compared to AOMTF children (p value < 0.04). Comparing acute to convalescent titers after AOM, otitis prone and AOMTF children had no significant change in total IgG against all the three proteins, while non-otitis prone children had significant increases to Protein D. Anti-protein D, P6 and OMP26 antibody levels measured longitudinally during NP colonization between age 6 and 24 months in 10 otitis prone children and 150 non-otitis prone children showed <2-fold increases over time in otitis prone children compared to >4 fold increases in the non-otitis prone children (p value < 0.001). We conclude that otitis prone children mount less of an IgG serum antibody response toward Protein D, P6 and OMP26 after AOM which may account for recurrent infections. The data on acute sera of otitis prone vs non-otitis prone children and the acute-to-convalescence response in non-otitis prone children point to a possible link of anti-PD to protection. Moreover, the data suggest that otitis prone children should be evaluated for their responses to Protein D, P6 and OMP26 vaccine antigens of NTHi.     

Potential use of a recombinant replication-defective adenovirus vector carrying the C-terminal portion of the P97 adhesin protein as a vaccine against Mycoplasma hyopneumoniae in swine

Mycoplasma hyopneumoniae causes severe economic losses to the swine industry worldwide and the prevention of its related disease, enzootic porcine pneumonia, remains a challenge. The P97 adhesin protein of M. hyopneumoniae should be a good candidate for the development of a subunit vaccine because antibodies produced against P97 could prevent the adhesion of the pathogen to the respiratory epithelial cells in vitro. In the present study, a P97 recombinant replication-defective adenovirus (rAdP97c) subunit vaccine efficiency was evaluated in pigs. The rAdP97c vaccine was found to induce both strong P97 specific humoral and cellular immune responses. The rAdP97c vaccinated pigs developed a lower amount of macroscopic lung lesions (18.5 ± 9.6%) compared to the unvaccinated and challenged animals (45.8 ± 11.5%). rAdP97c vaccine reduced significantly the severity of inflammatory response and the amount of M. hyopneumoniae in the respiratory tract. Furthermore, the average daily weight gain was slightly improved in the rAdP97c vaccinated pigs (0.672 ± 0.068 kg/day) compared to the unvaccinated and challenged animals (0.568 ± 0.104 kg/day). A bacterin-based commercial vaccine (Suvaxyn^® MH-one) was more efficient to induce a protective immune response than rAdP97c even if it did not evoke a P97 specific immune response. These results suggest that immunodominant antigens other than P97 adhesin are also important in the induction of a protective immune response and should be taken into account in the future development of M. hyopneumoniae subunit vaccines.     

Dyslipidaemia and insulin resistance in vertically HIV-infected children and adolescents

This cross-sectional study determined the influence of antiretroviral therapy (ART) on the lipid profile and insulin sensitivity of 119 perinatally HIV-infected Brazilian patients aged 6-19 years. Inadequate high-density lipoprotein cholesterol (HDL-c) concentrations were observed in 81.4% of patients. High concentrations of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c) and triglycerides (TG) were found in 33.9%, 9.7% and 35.6% of patients, respectively. There were statistically significant differences in mean concentrations of TC (P = 0.004), HDL-c (P = 0.015) and LDL-c (P = 0.028) among children (<10 years), early adolescents (10-14 years) and late adolescents (15-19 years). Children presented the highest mean concentrations of TC and LDL-c, and patients in late adolescence presented the lowest concentrations of HDL-c. Insulin sensitivity, assessed by the Homeostasis Model Assessment (HOMA) index, was diagnosed in 16.7% of patients, with a statistically higher proportion (P = 0.034) of insulin-resistant children (33.3%) compared with adolescents (12.5%). There was a statistically significant association between TG concentrations and use of ART regimens containing protease inhibitors (PI) (P = 0.0003). Children presented a higher prevalence of insulin resistance and dyslipidaemia compared with adolescents, suggesting that ART, especially PIs, may lead to metabolic complications.     

HIV-1 vaccine-specific responses induced by Listeria vector vaccines are maintained in mice subsequently infected with a model helminth parasite, Schistosoma mansoni

In areas co-endemic for helminth parasites and HIV/AIDS, infants are often administered vaccines prior to infection with immune modulatory helminth parasites. Systemic Th2 biasing and immune suppression caused by helminth infection reduces cell-mediated responses to vaccines such as tetanus toxoid and BCG. Therefore, we asked if infection with helminthes post-vaccination, alters already established vaccine induced immune responses. In our model, mice are vaccinated against HIV-1 Gag using a Listeria vaccine vector (Lm-Gag) in a prime-boost manner, then infected with the human helminth parasite Schistosoma mansoni. This allows us to determine if established vaccine responses are maintained or altered after helminth infection. Our second objective asked if helminth infection post-vaccination alters the recipient's ability to respond to a second boost. Here we compared responses between uninfected mice, schistosome infected mice, and infected mice that were given an anthelminthic, which occurred coincident with the boost or four weeks prior, as well as comparing to un-boosted mice. We report that HIV-1 vaccine-specific responses generated by Listeria vector HIV-1 vaccines are maintained following subsequent chronic schistosome infection, providing further evidence that Listeria vector vaccines induce potent vaccine-specific responses that can withstand helminth infection. We also were able to demonstrate that administration of a second Listeria boost, which markedly enhanced the immune response, was minimally impacted by schistosome infection, or anthelminthic therapy. Surprisingly, we also observed enhanced antibody responses to HIV Gag in vaccinated mice subsequently infected with schistosomes.