The prevalence of preexisting immunity to adenoviruses in the majority of the human population might adversely impact the development of adaptive immune responses against adenovirus vector-based vaccines. To address this issue, we primed BALB/c mice either intranasally (i.n.) or intramuscularly (i.m.) with varying doses of wild type (WT) human adenovirus subtype 5 (HAd5). Following the development of immunity against HAd5, we immunized animals via the i.n. or i.m. route of inoculation with a HAd vector (HAd-HA-NP) expressing the hemagglutinin (HA) and nucleoprotein (NP) of A/Vietnam/1203/ 04 (H5N1) influenza virus. The immunogenicity and protection results suggest that low levels of vector immunity (,520 virus-neutralization titer) induced by priming mice with up to 107 plaque forming units (p.f.u.) of HAd-WT did not adversely impact the protective efficacy of the vaccine. Furthermore, high levels of vector immunity (approximately 1500 virusneutralization titer) induced by priming mice with 108 p.f.u. of HAd-WT were overcome by either increasing the vaccine dose or using alternate routes of vaccination. A further increase in the priming dose to 109 p.f.u. allowed only partial protection. These results suggest possible strategies to overcome the variable levels of human immunity against adenoviruses, leading to better utilization of HAd vector-based vaccines.
Date of this Version
This is the publisher pdf of "Impact of Preexisting Adenovirus Vector Immunity on Immunogenicity and Protection Conferred with an Adenovirus-Based H5N1 Influenza Vaccine Aseem Pandey, Neetu Singh, Sai V. Vemula, Laurent Couëtil, Jacqueline M. Katz, Ruben Donis, Suryaprakash Sambhara, Suresh K. Mittal. PLOS ONE 2012 7(3): e33428. doi: doi:10.1371/journal.pone.0033428 " and is available at: 10.1371/journal.pone.0033428