Impact of Preexisting Adenovirus Vector Immunity on Immunogenicity and Protection Conferred with an Adenovirus-based H5N1 Influenza Vaccine
Overview
Authors
Affiliations
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 10(7) 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 virus-neutralization titer) induced by priming mice with 10(8) 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 10(9) 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.
Amoah S, Cao W, Sayedahmed E, Wang Y, Kumar A, Mishina M J Virol. 2024; 98(8):e0071124.
PMID: 39082839 PMC: 11334528. DOI: 10.1128/jvi.00711-24.
Triple tandem trimer immunogens for HIV-1 and influenza nucleic acid-based vaccines.
Moral-Sanchez I, Wee E, Xian Y, Lee W, Allen J, Torrents de la Pena A NPJ Vaccines. 2024; 9(1):74.
PMID: 38582771 PMC: 10998906. DOI: 10.1038/s41541-024-00862-8.
Sayedahmed E, Elshafie N, Zhang G, Mohammed S, Sambhara S, Mittal S Front Immunol. 2023; 14:1305937.
PMID: 38077380 PMC: 10702558. DOI: 10.3389/fimmu.2023.1305937.
Sayedahmed E, Araujo M, Silva-Pereira T, Chothe S, Elkashif A, Alhashimi M Mol Ther Methods Clin Dev. 2023; 30:194-207.
PMID: 37502665 PMC: 10299838. DOI: 10.1016/j.omtm.2023.06.009.
An Old Acquaintance: Could Adenoviruses Be Our Next Pandemic Threat?.
Saint-Pierre Contreras G, Conei Valencia D, Lizama L, Vargas Zuniga D, Avendano Carvajal L, Ampuero Llanos S Viruses. 2023; 15(2).
PMID: 36851544 PMC: 9966032. DOI: 10.3390/v15020330.