1,721,289 research outputs found
Factors influencing innate immunity and vaccine responses in infancy
No full textDespite significant progress in reducing the burden of mortality in children under the age of five, reducing mortality in newborns remains a major challenge. Infection plays a significant role in infant deaths and interventions such as early vaccination or antenatal immunization could make a significant contribution to prevention of such deaths. In the last fewyears, we have gained newinsights into immune ontogeny and are nowbeginning to understand the impact of vaccines, nutrition and environmental factors on ‘training0 of the immune response in early life. This review article sets out to explain why vaccine responses can be heterogeneous between populations and individuals by providing examples chosen to illustrate the impact of host, pathogen and environmental factors on shaping theimmune ‘interactome0 in young children
Maternal immunization as a strategy to decrease susceptibility to infection in newborn infants
No full textPurpose of Review: Following on from the success of maternal tetanus vaccination, recent research has shown that other vaccines given in pregnancy can protect against vaccine-preventable infections in early infancy. This review will outline these recent developments and highlight the impact on current clinical practice. RECENT FINDINGS: Maternal immunization provides protection to the newborn through the transfer of vaccine-induced IgG across the placenta, a process that is affected by multiple variables. The safety of newly recommended maternal vaccines has been further tested in recent studies. Maternal vaccination against influenza and pertussis is recommended in the United Kingdom and United States, with new studies indicating their efficacy. A number of additional maternal vaccines are also in the pipeline, which could be used to combat neonatal infection. Recent research findings have highlighted some of the reasons for the poor uptake of current recommendations among pregnant women. SUMMARY: Tetanus, influenza and pertussis vaccines are now recommended for use during pregnancy, with new vaccines, such as group B streptococcus and respiratory syncytial virus, being developed to prevent important neonatal infections in the future
Bridging the gap: Maternal immunisation as a means to reduce neonatal deaths from infectious diseases
No full textAlthough significant progress towards Millennium Goals 4 and 5 has been recorded, neonatal mortality remains a global challenge. There were an estimated 3·3 million neonatal deaths worldwide in 2009, accounting for a significant proportion of under-5-year mortality. Progress in this age group is now most urgently required.Citation1 Infectious diseases are the major cause of neonatal deaths and some can be prevented by vaccination, which is accepted as one of the most successful and cost-effective health interventions. However, to achieve full protection against infections requires multiple doses of vaccines given over several months in the first year of life.During this particularly vulnerable period of early infancy, newborns remain partially protected through transfer of immunoglobulins from the mother, which carry specific antibodies against infections or vaccine antigens that the mother had previously encountered. However, maternal levels of such specific immunoglobulin (IgG) are frequently sub-optimal.Citation2 Maternal immunisation represents a strategy that could be employed to ‘bridge the gap’ in protection: the aim is to enhance the antibody levels against a particular infectious disease by giving the vaccine to the pregnant woman, who will then transmit a protective level of antibody to her infant in utero and through breastmilk after birth. Multiple factors can affect the transfer of IgG across the placenta, including maternal IgG concentration, the IgG subtype, gestational age and maternal co-infections, such as HIV.Citation3 These factors, among others, also determine the level of immunity that an infant can obtain from a maternal vaccin
Immunizing Pregnant Women and Infants (IMPRINT) Network: building and sustaining an interdisciplinary network tackling the complex challenges of vaccination in pregnancy and early life
No full textImmunising Pregnant Women and Infants is a UK-funded, international research network that supports interdisciplinary research addressing key challenges in the best use of vaccines in pregnancy and in newborns. The goal of this short review paper is to introduce readers to the network’s aims and objectives and highlight its initiatives and outputs for research and innovation within the UK and in low- and middle-income countries. The long-term goal of this network is to contribute to improved maternal and newborn health globally through the safe and effective use of vaccines
Maternal HIV Infection and Antibody Responses in Uninfected Infants—Reply
No full textMs de Souza and colleagues are concerned about factors that may have biased our results. While it has been documented that breastfeeding may affect responses to vaccination, it is unlikely to account for the differences we observed between HIV-exposed and unexposed infants. The majority of published data suggests that breastfeeding enhances rather than reduces vaccine responses,1 specifically to diphtheria, tetanus, polio, BCG, and Haemophilus influenzae type b.2,3 Moon et al4 showed that higher levels of maternal IgA in breast milk can cause neutralization of live oral rotavirus antigens in vitro. We did not measure responses to rotavirus or any oral vaccine. We acknowledge that while breastfeeding may enhance the antibody response to some vaccines and potentially decrease the response to live oral vaccines, it would not explain our findings, namely increased responses among uninfected HIV-exposed infants to some vaccines, since all of these infants were exclusively formula fed. Therefore, we may in fact have underestimated the effect of HIV exposure on vaccine response
TB in children
No full textTuberculosis (TB) in childhood is under reported but represents a sentinel event of transmission in the community. Susceptibility to TB is age-dependent with young children at highest risk of disseminated disease. Age-related differences in immune responses to mycobacteria underlie this phenomenon. Since childhood TB tends to be paucibacillary, bacteriological confirmation is more difficult to achieve and accurate diagnosis remains a challenge. Diagnostics include measures of host sensitisation, such as the tuberculin skin test (TST) and interferon-γ release assay (IGRA), but their performance varies between children and adults and in the context of bacille Calmette-Guérin (BCG) vaccination. Therapeutic regimens are based on adult studies but increased doses have recently been recommended by the World Health Organization (WHO), following pharmacokinetic studies in children. TB/ HIV co-infection adds complexity to diagnosis and management, much like in adults. The BCG vaccine is not fully protective and is not recommended for HIV-infected children. New vaccines are currently under investigation, with trials including infants and adolescents.</p
Immunology and pathogenesis of childhood TB
No full textTuberculosis (TB) in children most commonly results from exposure to a household contact with active TB, and represents ongoing transmission of Mycobacterium Tuberculosis (Mtb) in the community.1 Infants and young children have an increased risk of infection following exposure and progress more readily from infection to active TB disease; in the absence of intervention, infants have a 50-60% risk of disease in the first year following infection.2, 3 It could therefore be argued that the determining factor for the higher susceptibility to disease in children is prolonged, intimate contact between the child and the index case, which might lead to a larger inoculum of Mtb. However, there is little evidence to support this assumption, since the mycobacterial load in children is notoriously low, which lies at the root of the problem of bacteriological confirmation of primary TB. Young children more commonly present with disseminated disease and have an increased risk of death.2 Even low bacillary loads in children can lead to acute and severe illness, be it respiratory or disseminated, especially in children younger than 2 years of age. The generally accepted assumption is therefore that qualitative and quantitative differences in the immune responses to Mtb infection between adults and children determine outcome. In the following review, we describe the multiple factors involved in containment of mycobacteria and review potential differences between responses in adults versus children. We have chosen to base this article primarily on studies conducted in the human host and - where available - in children. It is however obvious that crucial data on the impact of age on many of the cited factors are missing from the published literature, and we indicate where further studies would be warranted in this context
The relationship between concentration of specific antibody at birth and subsequent response to primary immunization
No full textBackground 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: rs -0.86 (95%CI -0.93 to -0.74), p<0.0001; pneumococcus: rs -0.82 (95% CI -0.91 to -0.67), p<0.0001; pertussis: rs -0.77 (95% CI -0.89 to -0.58), p<0.0001 and Hib: rs -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
Maternal HIV infection and antibody responses against vaccine-preventable diseases in uninfected infants
No full textContext: Altered immune responses might contribute to the high morbidity and mortality observed in human immunodeficiency virus (HIV)-exposed uninfected infants. Objective: To study the association of maternal HIV infection with maternal- and infant-specific antibody levels to Haemophilus influenzae type b (Hib), pneumococcus, Bordetella pertussis antigens, tetanus toxoid, and hepatitis B surface antigen. Design, Setting, and Participants: A community-based cohort study in Khayelitsha, Western Cape Province, South Africa, between March 3, 2009, and April 28, 2010, of 109 HIV-infected and uninfected women and their infants. Serum samples from 104 women and 100 infants were collected at birth and samples from 93 infants were collected at 16 weeks. Main Outcome Measure: Level of specific antibody in mother-infant pairs at delivery and in infants at 16 weeks, determined by enzyme-linked immunosorbent assays. Results: At birth, HIV-exposed uninfected infants (n=46) had lower levels of specific antibodies than unexposed infants (n=54) did to Hib (0.37 [interquartile range {IQR}, 0.22-0.67] mg/L vs 1.02 [IQR, 0.34-3.79] mg/L; P<.001), pertussis (16.07 [IQR, 8.87-30.43] Food and Drug Administration [FDA] U/mL vs 36.11 [IQR, 20.41-76.28] FDA U/mL; P<.001), pneumococcus (17.24 [IQR, 11.33-40.25] mg/L vs 31.97 [IQR, 18.58-61.80] mg/L; P=.02), and tetanus (0.08 [IQR, 0.03-0.39] IU/mL vs 0.24 [IQR, 0.08-0.92] IU/mL; P=.006). Compared with HIV-uninfected women (n=58), HIV-infected women (n=46) had lower specific antibody levels to Hib (0.67 [IQR, 0.16-1.54] mg/L vs 1.34 [IQR, 0.15-4.82] mg/L; P=.009) and pneumococcus (33.47 [IQR, 4.03-69.43] mg/L vs 50.84 [IQR, 7.40-118.00] mg/L; P=.03); however, no differences were observed for antipertussis or antitetanus antibodies. HIV-exposed uninfected infants (n=38) compared with HIV-unexposed infants (n=55) had robust antibody responses following vaccination, with higher antibody responses to pertussis (270.1 [IQR, 84.4-355.0] FDA U/mL vs 91.7 [IQR, 27.9-168.4] FDA U/mL; P=.006) and pneumoccocus (47.32 [IQR, 32.56-77.80] mg/L vs 14.77 [IQR, 11.06-41.08] mg/L; P=.001). Conclusion: Among South African infants, antenatal HIV exposure was associated with lower specific antibody responses in exposed uninfected infants compared with unexposed infants at birth, but with robust responses following routine vaccination
Specific antibodies against vaccine-preventable infections: a mother-infant cohort study
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