RESUMO
In the midst of new investigations into the mechanisms of both delivery and protection of new vaccines and vaccine carriers, it has become clear that immunization with delivery mechanisms that do not involve living, replicating organisms are vastly preferred. In this report, non-replicating bacterial minicells simultaneously co-delivering the nucleoprotein (NP) of lymphocytic choriomeningitis virus (LCMV) and the corresponding DNA vaccine were tested for the ability to generate protective cellular immune responses in mice. It was found that good protection (89%) was achieved after intramuscular administration, moderate protection (31%) was achieved after intranasal administration, and less protection (7%) was achieved following gastric immunization. These results provide a solid foundation on which to pursue the use of bacterial minicells as a non-replicating vaccine delivery platform.
Assuntos
Imunização/métodos , Coriomeningite Linfocítica/imunologia , Vírus da Coriomeningite Linfocítica/imunologia , Nucleoproteínas/imunologia , Vacinas de DNA/imunologia , Vacinas Virais/imunologia , Administração Intranasal , Animais , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Células COS , Chlorocebus aethiops , Citocinas/metabolismo , Citotoxicidade Imunológica/imunologia , Sistemas de Liberação de Medicamentos/métodos , Escherichia coli/virologia , Injeções Intramusculares , Coriomeningite Linfocítica/prevenção & controle , Vírus da Coriomeningite Linfocítica/genética , Vírus da Coriomeningite Linfocítica/crescimento & desenvolvimento , Camundongos , Camundongos Endogâmicos C57BL , Nucleoproteínas/genética , Células Vero , Vacinas Virais/administração & dosagem , Vacinas Virais/genéticaRESUMO
Recent events surrounding emerging infectious diseases, bioterrorism and increasing multidrug antibiotic resistance in bacteria have drastically increased current needs for effective vaccines. Many years of study have shown that live, attenuated pathogens are often more effective at delivering heterologous protein or DNA to induce protective immune responses. However, these vaccine carriers have inherent safety concerns that have limited their development and their use in many patient populations. Studies using nonliving delivery mechanisms have shown that providing both protein antigen and DNA encoding the antigen to an individual induces an improved, more protective immune response but rarely, if ever, are both delivered simultaneously. Here, non-replicating bacterial minicells derived from a commensal E. coli strain are shown to effectively induce antigen-specific immune responses after simultaneous protein and DNA delivery. These data demonstrate the potential use of achromosomal bacterial minicells as a vaccine carrier.