Safety and efficacy of neonatal vaccination

Department of Medicine, Division of Infectious Diseases, Children's Hospital Boston, Boston, MA 02115, USA.
European Journal of Immunology (Impact Factor: 4.03). 01/2009; 39(1):36-46. DOI: 10.1002/eji.200838620
Source: PubMed


Newborns have an immature immune system that renders them at high risk for infection while simultaneously reducing responses to most vaccines, thereby posing challenges in protecting this vulnerable population. Nevertheless, certain vaccines, such as BCG and Hepatitis B vaccine, do demonstrate safety and some efficacy at birth, providing proof of principal that certain antigen-adjuvant combinations are able to elicit protective neonatal responses. Moreover, birth is a major point of healthcare contact globally meaning that effective neonatal vaccines achieve high population penetration. Given the potentially significant benefit of vaccinating at birth, availability of a broader range of more effective neonatal vaccines is an unmet medical need and a public health priority. This review focuses on safety and efficacy of neonatal vaccination in humans as well as recent research employing novel approaches to enhance the efficacy of neonatal vaccination.

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    • "Th1 cells are effector and memory CD4+ T-cells polarized to produce interferon-c (IFN-c). Neonates and infants generally have reduced Th1 responses to many intracellular pathogens and toxins [1]. Neonatal BCG vaccination has also been reported to reduce neonatal and infant mortality due to diseases other than tuberculosis [2] [3] [4]. "
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    ABSTRACT: Neonatal Bacille Calmette Guérin (BCG) vaccination has been reported to have beneficial effects beyond preventing infantile tuberculous meningitis and miliary disease. We hypothesized that BCG vaccine given at birth would enhance T-helper 1 (Th1) immune responses to the first vaccines given later in infancy. We conducted a nested case-control study of neonatal BCG vaccination and its heterologous Th1 immune effects in 2–3 months old infants. BCG vaccination at birth was associated with an increased frequency of interferon-γ (IFN-γ) producing spot-forming cells (SFC) to tetanus toxoid 2–3 months later. The frequency of IFN-γ producing SFC to polioviruses 1–3 also trended higher among infants who received BCG vaccination at birth. The frequency of IFN-γ+/tumor necrosis factor-α (TNF-α)+CD45RO+CD4+ T-cells upon stimulation with phorbol myristate acetate (PMA)/Ionomycin was higher in 2–3 months old infants who received BCG vaccination at birth compared to those who did not. The circulating frequency of forkhead box P3 (FoxP3)+ CD45RO+ regulatory CD4+ T-cells also trended lower in these infants. Neonatal BCG vaccination is associated with heterologous Th1 immune effects 2–3 months later.
    Trials in Vaccinology 02/2014; 3(1):1–5. DOI:10.1016/j.trivac.2013.11.004
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    • "For the past decade, there has been an ongoing focus on understanding the mechanisms by which the immune system of very young is distinct from adults, particularly in response to immunization [5]. New insights into the ontogeny of innate immunity are informing development of age-specific adjuvanted vaccine formulations [6], [7], [8], with safety and efficacy remaining central priorities [9]. The coming decade is likely to focus on developing technologies that overcome or circumvent these immunological obstacles to the development of more effective early life vaccines [2]. "
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    ABSTRACT: Newborns display distinct immune responses that contribute to susceptibility to infection and reduced vaccine responses. Toll-like receptor (TLR) agonists may serve as vaccine adjuvants, when given individually or in combination, but responses of neonatal leukocytes to many TLR agonists are diminished. TLR8 agonists are more effective than other TLR agonists in activating human neonatal leukocytes in vitro, but little is known about whether different TLR8 agonists may distinctly activate neonatal leukocytes. We characterized the in vitro immuno-stimulatory activities of a novel benzazepine TLR8 agonist, VTX-294, in comparison to imidazoquinolines that activate TLR8 (R-848; (TLR7/8) CL075; (TLR8/7)), with respect to activation of human newborn and adult leukocytes. Effects of VTX-294 and R-848 in combination with monophosphoryl lipid A (MPLA; TLR4) were also assessed. TLR agonist specificity was assessed using TLR-transfected HEK293 cells expressing a NF-κB reporter gene. TLR agonist-induced cytokine production was measured in human newborn cord and adult peripheral blood using ELISA and multiplex assays. Newborn and adult monocytes were differentiated into monocyte-derived dendritic cells (MoDCs) and TLR agonist-induced activation assessed by cytokine production (ELISA) and co-stimulatory molecule expression (flow cytometry). VTX-294 was ∼100x more active on TLR8- than TLR7-transfected HEK cells (EC50, ∼50 nM vs. ∼5700 nM). VTX-294-induced TNF and IL-1β production were comparable in newborn cord and adult peripheral blood, while VTX-294 was ∼ 1 log more potent in inducing TNF and IL-1β production than MPLA, R848 or CL075. Combination of VTX-294 and MPLA induced greater blood TNF and IL-1β responses than combination of R-848 and MPLA. VTX-294 also potently induced expression of cytokines and co-stimulatory molecules HLA-DR and CD86 in human newborn MoDCs. VTX-294 is a novel ultra-potent TLR8 agonist that activates newborn and adult leukocytes and is a candidate vaccine adjuvant in both early life and adulthood.
    PLoS ONE 03/2013; 8(3):e58164. DOI:10.1371/journal.pone.0058164 · 3.23 Impact Factor
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    • "However, vaccines consisting of purified microbial subunits often lack the necessary adjuvant activity to induce and optimally shape an immune response. Most of the vaccines currently given early in life are examples of such subunit vaccines [7] [8] [9] [10]. Inclusion of adjuvants has been key to the efficacy of these subunit vaccine formulations [11]. "
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    ABSTRACT: Subunit vaccine formulations often include adjuvants that primarily stimulate innate immune cells. While young infants represent the major target population for vaccination, effective immunization in this age group remains a challenge. Many parameters of innate immune responses differ quantitatively and qualitatively from newborns to infants and adults, revealing a highly regulated developmental program. Herein, we discuss the potential implications of innate immune ontogeny for the activity of adjuvants contained in licensed infant vaccines, as well as future directions for rational design of adjuvanted vaccines for this age group.
    Vaccine 10/2012; 31(21). DOI:10.1016/j.vaccine.2012.10.016 · 3.62 Impact Factor
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