Mucosal immunization with integrase-defective lentiviral vectors protects against influenza virus challenge in mice.
Recent reports highlight the potential for integrase-defective lentiviral vectors (IDLV) to be developed as vaccines due to their ability to elicit cell-mediated and humoral immune responses after intramuscular administration. Differently from their integrase-competent counterpart, whose utility for vaccine development is limited by the potential for insertional mutagenesis, IDLV possess a mutation in their integrase gene that prevents genomic integration. Instead, they are maintained as episomal DNA circles that retain the ability to stably express functional proteins. Despite their favorable profile, it is unknown whether IDLV elicit immune responses after intranasal administration, a route that could be advantageous in the case of infection with a respiratory agent. Using influenza as a model, we constructed IDLV expressing the influenza virus nucleoprotein (IDLV-NP), and tested their ability to generate NP-specific immune responses and protect from challenge in vivo. We found that administration of IDLV-NP elicited NP-specific T cell and antibody responses in BALB/c mice. Importantly, IDLV-NP was protective against homologous and heterosubtypic influenza virus challenge only when given by the intranasal route. This is the first report demonstrating that IDLV can induce protective immunity after intranasal administration, and suggests that IDLV may represent a promising vaccine platform against infectious agents.
Department of Public Health, Weill Medical College of Cornell University, New York, New York, United States of America.
Judith M
JM
Fontana
Department of Public Health, Weill Medical College of Cornell University, New York, New York, United States of America.
Paul J
PJ
Christos
Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy.
Zuleika
Z
Michelini
Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità, Rome, Italy.
Donatella
D
Negri
Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy.
Andrea
A
Cara
Department of Public Health, Weill Medical College of Cornell University, New York, New York, United States of America; Department of Medicine, Weill Medical College of Cornell University, New York, New York, United States of America.
Mirella
M
Salvatore
D000281:Administration, Intranasal; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D004285:Dogs; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D005434:Flow Cytometry; D005822:Genetic Vectors / Q000008:administration & dosage / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D018928:Immunity, Mucosal; D009980:Influenza A virus; D019426:Integrases / Q000378:metabolism*; D016086:Lentivirus; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D009698:Nucleoproteins / Q000008:administration & dosage / Q000494:pharmacology*; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*; D010957:Plasmids / Q000235:genetics
D009698:Nucleoproteins; D019426:Integrases