Development of newborn and infant vaccines.

Children's Hospital Boston, Boston, MA 02115, USA.
Science translational medicine (Impact Factor: 14.41). 07/2011; 3(90):90ps27. DOI: 10.1126/scitranslmed.3001880
Source: PubMed

ABSTRACT Vaccines for early-life immunization are a crucial biomedical intervention to reduce global morbidity and mortality, yet their developmental path has been largely ad hoc, empiric, and inconsistent. Immune responses of human newborns and infants are distinct and cannot be predicted from those of human adults or animal models. Therefore, understanding and modeling age-specific human immune responses will be vital to the rational design and development of safe and effective vaccines for newborns and infants.

Download full-text


Available from: Ofer Levy, Aug 09, 2015
  • Source
    • "DLS showed that the size of Gag:PCPP complexes was ~90 nm in diameter, a size range associated with successful uptake and antigen presentation by APCs, as also demonstrated in our study in both newborn and adult MoDCs. Neonatal immunization is hindered by distinct innate and adaptive responses including diminished antigen presentation, reduced IFN-g production, and sub-optimal antibody maturation and affinity [27]. In many developing countries birth is the first e and often the only e point of healthcare contact, motivating development of neonatal vaccines. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Neonates and infants are susceptible to infection due to distinct immune responses in early life. Therefore, development of vaccine formulation and delivery systems capable of activating human newborn leukocytes is of global health importance. Poly[di(carboxylatophenoxy)phosphazene] (PCPP) belongs to a family of ionic synthetic polyphosphazene polyelectrolyte compounds that can form non-covalent interactions with protein antigens and demonstrate adjuvant activity in animals and in human clinical trials. However, little is known about their ability to activate human immune cells. In this study, we characterized the effects of PCPP alone or in combination with a model antigen (recombinant HIV-Gag (Gag)), on the maturation, activation and antigen presentation by human adult and newborn dendritic cells (DCs) in vitro. PCPP treatment induced DC activation as assessed by upregulation of co-stimulatory molecules and cytokine production. Studies benchmarking PCPP to Alum, the most commonly used vaccine adjuvant, demonstrated that both triggered cell death and release of danger signals in adult and newborn DCs. When complexed with Gag antigen, PCPP maintained its immunostimulatory characteristics while permitting internalization and presentation of Gag by DCs to HIV-Gag-specific CD4(+) T cell clones. The PCPP vaccine formulation outlined here has intrinsic adjuvant activity, can facilitate effective delivery of antigen to DCs, and may be advantageous for induction of beneficial T cell-mediated immunity. Moreover, polyphosphazenes can further reduce cost of vaccine production and distribution through their dose-sparing and antigen-stabilizing properties, thus potentially eliminating the need for cold chain distribution.
    Biomaterials 07/2014; 35(31). DOI:10.1016/j.biomaterials.2014.06.043 · 8.31 Impact Factor
  • Source
    • "Inclusion of adjuvants has been key to the efficacy of these subunit vaccine formulations [11]. It is surprising that for most adjuvants we still lack insight into if and how their impact changes in an age-dependent manner [7] [12] [13]. Only in recent years has the development of the innate immune system, and in particular the response to danger-or pathogen associated molecular patterns (DAMPs or PAMPs) from birth onward, received attention. "
    [Show abstract] [Hide abstract]
    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. DOI:10.1016/j.vaccine.2012.10.016 · 3.49 Impact Factor
  • Source
    • "We will not spend much time on the immunological concepts and problems with RSV vaccination, or on vaccination of the newborns and infants, in general. Instead, we would refer the reader to several excellent recent reviews of these subjects [145] [146] [147] [148]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Respiratory syncytial virus (RSV) is the most significant cause of pediatric respiratory infections. Palivizumab (Synagis®), a humanized monoclonal antibody, has been used successfully for a number of years to prevent severe RSV disease in at-risk infants. However, despite intense efforts, there is no approved vaccine or small molecule drug for RSV. As an enveloped virus, RSV must fuse its envelope with the host cell membrane, which is accomplished through the actions of the fusion (F) glycoprotein, with attachment help from the G glycoprotein. Because of their integral role in initiation of infection and their accessibility outside the lipid bilayer, these proteins have been popular targets in the discovery and development of antiviral compounds and vaccines against RSV. This review examines advances in the development of antiviral compounds and vaccine candidates.
    02/2012; 12(2):110-28. DOI:10.2174/187152612800100143
Show more