B-cell responses to vaccination at the extreme of age

Departments of Pathology-Immunology and Pediatrics, WHO Collaborative Center for Neonatal Vaccinology, Medical Faculty of University of Geneva, Centre Medical Universitaire, Geneva 4, Switzerland.
Nature Reviews Immunology (Impact Factor: 34.99). 04/2009; 9(3):185-94. DOI: 10.1038/nri2508
Source: PubMed


Infants and the elderly share a high vulnerability to infections and therefore have specific immunization requirements. Inducing potent and sustained B-cell responses is as challenging in infants as it is in older subjects. Several mechanisms to explain the decreased B-cell responses at the extremes of age apply to both infants and the elderly. These include intrinsic B-cell limitations as well as numerous microenvironmental factors in lymphoid organs and the bone marrow. This Review describes the mechanisms that shape B-cell responses at the extremes of age and how they could be taken into account to design more effective immunization strategies for these high-risk age groups.

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Available from: Richard Aspinall
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    • "While neonates have some capacity for cell-mediated immunity [12], humoral immunity is very limited in early life [13]. Antibody responses in neonates are shorter, delayed in onset and of lower affinity than those observed in healthy adults [14]. The transfer of maternal IgG antibody to the fetus during pregnancy confers short-term passive immunity and represents a primary mechanism for protection against infectious diseases at birth [11]. "
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    ABSTRACT: Background: Shigella sonnei is an emergent and major diarrheal pathogen for which there is currently no vaccine. We aimed to quantify duration of maternal antibody against S. sonnei and investigate transplacental IgG transfer in a birth cohort in southern Vietnam. Methods and results: Over 500-paired maternal/infant plasma samples were evaluated for presence of anti-S. sonnei-O IgG and IgM. Longitudinal plasma samples allowed for the estimation of the median half-life of maternal anti-S. sonnei-O IgG, which was 43 days (95% confidence interval: 41-45 days). Additionally, half of infants lacked a detectable titer by 19 weeks of age. Lower cord titers were associated with greater increases in S. sonnei IgG over the first year of life, and the incidence of S. sonnei seroconversion was estimated to be 4/100 infant years. Maternal IgG titer, the ratio of antibody transfer, the season of birth and gestational age were significantly associated with cord titer. Conclusions: Maternal anti-S. sonnei-O IgG is efficiently transferred across the placenta and anti-S. sonnei-O maternal IgG declines rapidly after birth and is undetectable after 5 months in the majority of children. Preterm neonates and children born to mothers with low IgG titers have lower cord titers and therefore may be at greater risk of seroconversion in infancy.
    Preview · Article · Dec 2015 · Vaccine
    • "The current understanding for generation of robust antibodies from B cells requires 'help' from T helper cells in the form of cytokines, in particular Th2 cytokines (i.e. IL-4, IL-5, IL-6, IL-9, IL-10, IL-13) to assist in maturation of naïve B cells into effector cells (plasma cells) and memory B cells [59]. This is likely the case for HPV vaccination for the generation of long-lived HPV-specific B cell memory responses for long-term protection. "
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    ABSTRACT: Human papillomavirus (HPV) infection is the primary cause of genital warts, some oropharyngeal cancers and anogenital cancers, including cervical, vagina, vulvar, anal and penile cancers. Primary prevention of cervical cancer requires the prevention of high-risk HPV infections, particularly HPV genotypes 16 and 18. Both Gardasil(®) and Cervarix(®) vaccines when administered by a three-dose schedule have been demonstrated to be effective against cervical, vulva, and vagina cancer precursors from vaccine genotypes in phase III clinical trials, and post-marketing studies; Gardasil(®) vaccine also offer additional protection against anal cancer precursors. However, high costs of HPV vaccines and the logistics of delivering a three-dose schedule over 6 months are challenging in countries with limited resources. Several studies have demonstrated non-inferiority in antibody response between adolescents (9-15 years old) who received two doses (6 months apart) and women (>15 years old) who received the standard three-dose schedule. These studies provided evidence for the World Health Organization and European Medical Association to revise its recommendation to give two instead of three doses of HPV vaccine to adolescents below 15 years of age, provided the 2nd dose is given 6 months apart. Although reduced dose schedules can alleviate costs and logistics associated with HPV vaccination, especially in resource-poor countries, there are still gaps in this area of research, particularly regarding long-term protection. This review discusses the findings on antibody response and clinical outcomes in studies evaluating reduced dose HPV schedules, and highlights the important considerations of its implementation. In addition, other important immunological biomarkers that may be associated with long-term protection are highlighted and discussed. Copyright © 2015. Published by Elsevier Ltd.
    No preview · Article · Aug 2015 · Vaccine
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    • "A number of studies have determined that the immaturity of the immune system is most pronounced after birth and is overcome as the child develops. The immaturity (inability to fully respond to an antigenic stimulus) of the neonatal immune system has been observed in humans (1) and a number of other species, e.g., pig (2), cow (3, 4), and horse (5), and in experimental rodent models like mouse (1), rat (6), and cotton rat (7, 8). "
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    ABSTRACT: Neonates have an immature immune system, which cannot adequately protect against infectious diseases. Early in life, immune protection is accomplished by maternal antibodies transferred from mother to offspring. However, decaying maternal antibodies inhibit vaccination as is exemplified by the inhibition of seroconversion after measles vaccination. This phenomenon has been described in both human and veterinary medicine and is independent of the type of vaccine being used. This review will discuss the use of animal models for vaccine research. I will review clinical solutions for inhibition of vaccination by maternal antibodies, and the testing and development of potentially effective vaccines. These are based on new mechanistic insight about the inhibitory mechanism of maternal antibodies. Maternal antibodies inhibit the generation of antibodies whereas the T cell response is usually unaffected. B cell inhibition is mediated through a cross-link between B cell receptor (BCR) with the Fcγ-receptor IIB by a vaccine-antibody complex. In animal experiments, this inhibition can be partially overcome by injection of a vaccine-specific monoclonal IgM antibody. IgM stimulates the B cell directly through cross-linking the BCR via complement protein C3d and antigen to the complement receptor 2 (CR2) signaling complex. In addition, it was shown that interferon alpha binds to the CD21 chain of CR2 as well as the interferon receptor and that this dual receptor usage drives B cell responses in the presence of maternal antibodies. In lieu of immunizing the infant, the concept of maternal immunization as a strategy to protect neonates has been proposed. This approach would still not solve the question of how to immunize in the presence of maternal antibodies but would defer the time of infection to an age where infection might not have such a detrimental outcome as in neonates. I will review successful examples and potential challenges of implementing this concept.
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