CPB 697 RESEARCH SEMINAR
Neetu Singh, BVSC & AH, MVSc
Graduate Student in Molecular Virology
Department of Comparative Pathobiology
“Bovine Adenoviral Vector-Based H5N1 Influenza
Vaccine Overcomes
Exceptionally
High Levels Of Pre-Existing Immunity Against Human
Adenovirus”
Thursday, October 18, 2007
VPTH 112
3:30 pm
ABSTRACT:
Due to high prevalence of adenovirus infections in humans, it is believed that preexisting adenoviral neutralizing antibodies (popularly know as ‘vector immunity’) may negatively impact the immune response to vaccine antigens when delivered by human adenoviral vectors. In order to evaluate whether bovine adenovirus subtype 3 (BAd3), a nonhuman adenoviral vector, will effectively elude high levels of preexisting vector immunity, naïve or human adenovirus serotype 5 (HAd)-primed mice were immunized with BAd-H5HA [BAd3 vector expressing the hemagglutinin (HA) gene from H5N1 influenza virus]. Mice immunized with HAd-H5HA (HAd5 vector expressing H5N1 HA) served as a positive control. Even in the presence of very high levels of HAd-specific neutralizing antibody, no significant reductions in HA-specific humoral and cell-mediated immune responses were observed in HAd-primed mice immunized with BAd-H5HA. Naïve mice immunized with HAd-H5HA and boosted with BAd-H5HA elicited significantly (P<0.05) higher humoral and comparable cell-mediated immune responses compared to homologous prime-boost with either HAd-H5HA or BAd-H5HA alone, suggesting the importance heterologous prime-boost approach for an enhanced immune response. Naïve or HAd-primed mice immunized with BAd-H5HA were fully protected from morbidity and mortality following a lethal challenge with antigentically similar H5N1 virus (A/Hong Kong/483/97). These data suggest that exceptionally high levels of HAd-vector immunity do not adversely affect protective immune responses induced by BAd vector based H5N1 vaccine and demonstrate the importance of BAd vectors as an alternate or supplement to HAd vectors for influenza pandemic preparedness.