tetano
Editor, Senior Moderator
Mol Ther Methods Clin Dev. 2018 Jul 17;10:210-222. doi: 10.1016/j.omtm.2018.07.007. eCollection 2018 Sep 21.
[h=1]A Bovine Adenoviral Vector-Based H5N1 Influenza -Vaccine Provides Enhanced Immunogenicity and Protection at a Significantly Low Dose.[/h] Sayedahmed EE[SUP]1[/SUP], Hassan AO[SUP]1[/SUP], Kumari R[SUP]1[/SUP], Cao W[SUP]2[/SUP], Gangappa S[SUP]2[/SUP], York I[SUP]2[/SUP], Sambhara S[SUP]2[/SUP], Mittal SK[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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[SUP]7[/SUP] plaque-forming units (PFUs), whereas a significant amount of influenza virus was detected in the lungs of mice immunized with 1 ? 10[SUP]8[/SUP] 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[SUP]6[/SUP] PFUs), but similar protection with HAd-H5HA was observed at the highest vaccine dose (1 ? 10[SUP]8[/SUP] PFUs). These results suggest that at least 30-fold dose sparing can be achieved with BAd-H5HA vector compared with HAd-H5HA vaccine vector.
[h=4]KEYWORDS:[/h] adenoviral vector; avian influenza; bovine adenoviral vector; dose sparing; enhanced immunogenicity and protection; human adenoviral vector; route of immunization; universal influenza vaccine
PMID: 30101154 PMCID: PMC6082999 DOI: 10.1016/j.omtm.2018.07.007
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[h=1]A Bovine Adenoviral Vector-Based H5N1 Influenza -Vaccine Provides Enhanced Immunogenicity and Protection at a Significantly Low Dose.[/h] Sayedahmed EE[SUP]1[/SUP], Hassan AO[SUP]1[/SUP], Kumari R[SUP]1[/SUP], Cao W[SUP]2[/SUP], Gangappa S[SUP]2[/SUP], York I[SUP]2[/SUP], Sambhara S[SUP]2[/SUP], Mittal SK[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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[SUP]7[/SUP] plaque-forming units (PFUs), whereas a significant amount of influenza virus was detected in the lungs of mice immunized with 1 ? 10[SUP]8[/SUP] 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[SUP]6[/SUP] PFUs), but similar protection with HAd-H5HA was observed at the highest vaccine dose (1 ? 10[SUP]8[/SUP] PFUs). These results suggest that at least 30-fold dose sparing can be achieved with BAd-H5HA vector compared with HAd-H5HA vaccine vector.
[h=4]KEYWORDS:[/h] adenoviral vector; avian influenza; bovine adenoviral vector; dose sparing; enhanced immunogenicity and protection; human adenoviral vector; route of immunization; universal influenza vaccine
PMID: 30101154 PMCID: PMC6082999 DOI: 10.1016/j.omtm.2018.07.007
Free full text