Human Adenovirus Serotype 3 Vector Packaged by a Rare Serotype 14 Hexon

Area of Science:

• Virology
• Immunology
• Gene Therapy

Background:

• Recombinant adenovirus serotype 3 (rAd3) uses desmoglein 2 (DSG2) for cell entry and is explored for gene therapy and vaccination.
• Pre-existing immunity against adenovirus vectors can hinder their clinical application.

Purpose of the Study:

• To assess seroprevalence and neutralizing antibody (NAb) titers against adenovirus serotypes 3, 7, and 14 in southern China.
• To develop and evaluate a chimeric adenovirus vector (rAd3H14) designed to overcome pre-existing anti-adenovirus immunity.

Main Methods:

• Sera from healthy adults in southern China were tested for neutralizing antibodies against Ad3, Ad7, and Ad14.
• A chimeric adenovirus, rAd3H14, was constructed by replacing the hexon of rAd3EGFP with that of Ad14.
• In vitro neutralization assays and in vivo immunogenicity studies in mice with pre-existing anti-Ad3 immunity were performed.

Main Results:

• High seroprevalence against Ad3 (80.00%) and Ad7 (85.83%) was observed, with lower prevalence against Ad14 (22.50%).
• Significant proportions of the population had high-titer neutralizing antibodies against Ad3 (19.17%) and Ad7 (25.83%).
• The chimeric rAd3H14 vector demonstrated resistance to Ad3 neutralizing antibodies in vitro and induced robust anti-EGFP antibody responses in immune mice.

Conclusions:

• The chimeric adenovirus rAd3H14 effectively evades pre-existing Ad3 neutralizing antibodies.
• rAd3H14 represents a potential alternative vector for gene therapy and vaccination in populations with high Ad3 immunity.