ABSTRACT
Highly pathogenic avian H5N1 influenza viruses that are currently circulating in southeast Asia may acquire the potential to cause the next influenza pandemic. A number of alternate approaches are being pursued to generate cross-protective, dose-sparing, safe, and effective vaccines, as traditional vaccine approaches, i.e., embryonated egg-grown, are not immunogenic. We developed a replication-incompetent adenoviral vector-based, adjuvant- and egg-independent pandemic influenza vaccine strategy as a potential alternative to conventional egg-derived vaccines. In this paper, we address suboptimal dose and longevity of vaccine-induced protective immunity and demonstrate that a vaccine dose as little as 1 x 10(6) plaque-forming unit (PFU) is sufficient to induce protective immune responses against a highly pathogenic H5N1 virus. Furthermore, the vaccine-induced humoral and cellular immune responses and protective immunity persisted at least for a year.
Subject(s)
Adenoviridae , Antibodies, Viral , Disease Outbreaks/prevention & control , Influenza A Virus, H5N1 Subtype/immunology , Influenza Vaccines/immunology , Influenza, Human/prevention & control , Adjuvants, Immunologic , Animals , Antibodies, Viral/biosynthesis , Antibodies, Viral/immunology , Antibody Formation , Drug Design , Eggs , Genetic Vectors , Humans , Immunity, Cellular , Influenza A Virus, H5N1 Subtype/pathogenicity , Influenza, Human/epidemiology , Mice , Mice, Inbred BALB C , Time FactorsABSTRACT
Autoantibody production increases with ageing. However, the pathological significance of this increase as well as the corresponding underlying mechanisms are poorly understood. To further our understanding of the role that ageing plays in the development of autoantibody responses, we used a novel nonhuman primate model consisting of healthy baboons of ages representing the entire lifespan of this animal species. Results from this study indicate that production of antinuclear antibodies, anticell extract antibodies and natural autoantibodies gradually and significantly increases from young age to old age without a corresponding increase in neither serum immunoglobulin concentration nor in levels of selected markers of immune dysregulation (sTNF-RI, sTNF-RII, IL-2 sR alpha and IFN-gamma). Therefore, in the baboon model, autoantibodies may be produced in absence of recognizable pathological conditions of the ageing immune system.
