title: Immunogenicity and efficacy of a plasmid DNA rabies vaccine incorporating Myd88 as a genetic adjuvant.
abstract: OBJECTIVE
  Myeloid differentiation factor 88 (Myd88), a ubiquitous Toll-like receptor adaptor molecule, has been reported to play important roles in B cell responses to infections and vaccination. The present study evaluated the effects of genetic adjuvanting with Myd88 on the immune responses to a plasmid DNA rabies vaccine.
  
  
  METHODS
  Plasmids encoding rabies glycoprotein alone (pIRES-Rgp) or a fragment of Myd88 gene in addition (pIRES-Rgp-Myd) were constructed and administered intramuscularly or intrademally in Swiss albino mice (on days 0, 7, and 21). Rabies virus neutralizing antibody (RVNA) titres were estimated in the mice sera on days 14 and 28 by rapid fluorescent focus inhibition test. The protective efficacy of the constructs was evaluated by an intracerebral challenge with challenge virus standard virus on day 35.
  
  
  RESULTS
  Co-expression of Myd88 increased RVNA responses to pIRES-Rgp by 3- and 2-folds, following intramuscular and intradermal immunization, respectively. pIRES-Rgp protected 80% of the mice following intramuscular and intradermal immunizations, while pIRES-Rgp-Myd afforded 100% protection following similar administrations.
  
  
  CONCLUSIONS
  Genetic adjuvanting with Myd88 enhanced the RVNA responses and protective efficacy of a plasmid DNA rabies vaccine. This strategy might be useful for rabies vaccination of canines in the field, and needs further evaluation.
authors.affiliation: Department of Neurovirology, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India.
authors.forename: Padinjaremattathil Thankappan
authors.initials: PT
authors.lastname: Ullas
authors.affiliation: Department of Neurovirology, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India.
authors.forename: Anita
authors.initials: A
authors.lastname: Desai
authors.affiliation: Department of Neurovirology, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India.
authors.forename: Shampur Narayan
authors.initials: SN
authors.lastname: Madhusudana
keywords: Adjuvants; DNA vaccines; Myeloid differentiation factor 88; Rabies