Abstract
(English)
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The objectives of Neovac-EC are :1) to increase knowledge of immunological factors which, in early infancy, lead to a high susceptibility to infectious diseases and to relatively weak vaccine-induced responses; 2) to define optimal vaccine design and new immunization strategies for the rapid induction, in early life, of protective vaccine responses and long lasting immunological memory; 3) to identify and standardize suitable evaluation procedures (in vitro / in vivo, animal models / human, Dendritic Cell (DC), T and B cells responses) for the initial assessment of future vaccines / delivery systems / adjuvants considered for use in early life.Our own contribution to this project include training and technical transfer of our expertise in the area of neonatal murine vaccinology to several partners, in addition to our direct scientific contribution to several workpackages, which can be summarized as follows :1) We have identified a novel non-replicative antigen delivery systems able induce adult-like neonatal cytotoxic responses, as characterized by their frequency, their cytolytic capacity, their cytokine production and their protective efficacy. Importantly, these responses have been obtained without any adjuvant and do not depend from the presence or help of CD4+ T cells. This work has been recently submitted for publication.2) We have adapted an infant mice animal model which correlates with induction of infant responses to pertussis vaccines to the neonatal period, and used this model to assess the potential for neonatal immunisation. We have obtained excellent protective responses with a 2-dose vaccine schedule initiated in the neonatal period, despite age-dependent immune responses. This work has been recently submitted for publication.3) We have studied the immunogenic properties of ISCOMS to induce adult-like early life immune responses to RSV antigens (F and G proteins) and have observed induction of some cytotoxic responses but of limited antibody responses in early life. Work is ongoing to specify the characteristics / limitations of three distinct ISCOMS formulations.Thus, significant progress has been made during the first 2 years of the project : useful models have been implemented and developped, and results are promising for the capacity of new vectors / delivery systems to induce adult-like protective efficacy already in early life.
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