A Bovine Adenoviral Vector-Based H5N1 Influenza -Vaccine Provides Enhanced Immunogenicity and Protection at a Significantly Low Dose

Details

• Alternative Title:
  Mol Ther Methods Clin Dev
• Personal Author:
  Sayedahmed, Ekramy E. ; Hassan, Ahmed O. ; Kumari, Rashmi ; Cao, Weiping ; Gangappa, Shivaprakash ; York, Ian ; Sambhara, Suryaprakash ; Mittal, Suresh K.
• Description:
  Several human and nonhuman adenovirus (AdV) vectors including bovine AdV type 3 (BAdV-3) were developed as gene delivery vectors to supplement and/or elude human AdV (HAdV)-specific neutralizing antibodies (vector immunity). Here we evaluated the vaccine immunogenicity and efficacy of BAdV-3 vector (BAd-H5HA) expressing hemagglutinin (HA) of a H5N1 influenza virus in a dose escalation study in mice with the intranasal (IN) or intramuscular (IM) route of inoculation in comparison with the HAdV type C5 (HAdV-C5) vector (HAd-H5HA) expressing HA of a H5N1 influenza virus. Dose-related increases in the immune responses were clearly noticeable. A single IM inoculation with BAd-H5HA resulted in enhanced cellular immune responses compared with that of HAd-H5HA and conferred complete protection following challenge with a heterologous H5N1 virus at the dose of 3 × 10| plaque-forming units (PFUs), whereas a significant amount of influenza virus was detected in the lungs of mice immunized with 1 × 10| PFUs of HAd-H5HA. Similarly, compared with that of HAd-H5HA, a single IN inoculation with BAd-H5HA produced significantly enhanced humoral (HA-specific immunoglobulin [IgG] and its subclasses, as well as HA-specific IgA) and cellular immune responses, and conferred complete protection following challenge with a heterologous H5N1 virus. Complete protection with BAd-H5HA was observed with the lowest vaccine dose (1 × 10| PFUs), but similar protection with HAd-H5HA was observed at the highest vaccine dose (1 × 10| PFUs). These results suggest that at least 30-fold dose sparing can be achieved with BAd-H5HA vector compared with HAd-H5HA vaccine vector.
• Subjects:
  Adenoviral Vector Article Avian Influenza Bovine Adenoviral Vector Dose Sparing Enhanced Immunogenicity And Protection Human Adenoviral Vector Route Of Immunization Universal Influenza Vaccine
• Source:
  Mol Ther Methods Clin Dev. 2018; 10:210-222.
• Pubmed ID:
  30101154
• Pubmed Central ID:
  PMC6082999
• Document Type:
  Journal Article
• Funding:
  R01 AI059374/AI/NIAID NIH HHS/United States
• Volume:
  10
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:5d342e28460284bdbdf2b385a6bb078a1fb665f9802e44aca3d346dc388da8cc
• Download URL:
  https://stacks.cdc.gov/view/cdc/58233/cdc_58233_DS1.pdf
• File Type:
  [PDF - 2.48 MB ]