Human Adenovirus Serotype 3 Vector Packaged by a Rare Serotype 14 Hexon.
Recombinant adenovirus serotype 3 (rAd3), which infects cells through the receptor desmoglein 2 (DSG2), has been investigated as a vector for gene therapy or vaccination. However, pre-existing anti-vector immunity may limit the practical application of rAd3. In this study, we investigated the seroprevalence and neutralizing antibody (NAb) titers to Ad3 and alternate serotypes in normal healthy adults in southern China. Sera samples had a high seroprevalence (80.00%) against Ad3 and Ad7 (85.83%), compared with Ad14 (22.50%). Furthermore, 19.17% and 25.83% of samples had high-titer neutralizing antibodies to Ad3 and Ad7, respectively, compared with 3.33% against Ad14. We constructed a chimeric adenovirus, rAd3H14, designed to evade anti-vector immunity by replacing the enhanced green fluorescent protein (EGFP)-expressing hexon of the rAd3EGFP vector with a hexon from Ad14. The chimeric vector rAd3H14 was not neutralized in vitro efficiently by Ad3 NAbs using sera from mice and normal healthy human volunteers. Furthermore, in contrast to the unmodified vector rAd3EGFP, rAd3H14 induced robust antibody responses against EGFP in mice with high levels of pre-existing anti-Ad3 immunity. In conclusion, the chimeric vector rAd3H14 may be a useful alternative vector in adult populations with a high prevalence of Ad3 NAbs.
Department of Medical Genetics and Cell Biology, School of Basic Science, Guangzhou Medical University, Guangzhou 511436, P.R. China.
Xiaobo
X
Su
State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510120, P.R. China.
Xingui
X
Tian
Dongguan Institute of Pediatrics, Dongguan Children's Hospital, Dongguan 523325, P.R. China.
Zaixue
Z
Jiang
Dongguan Institute of Pediatrics, Dongguan Children's Hospital, Dongguan 523325, P.R. China.
Qiang
Q
Ma
Dongguan Institute of Pediatrics, Dongguan Children's Hospital, Dongguan 523325, P.R. China.
Qian
Q
Liu
Dongguan Institute of Pediatrics, Dongguan Children's Hospital, Dongguan 523325, P.R. China.
Xiaomei
X
Lu
State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510120, P.R. China.
Rong
R
Zhou
D000260:Adenoviruses, Human / Q000145:classification* / Q000276:immunology*; D000328:Adult; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D036022:Capsid Proteins / Q000378:metabolism*; D005260:Female; D005822:Genetic Vectors / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D056724:Immunity, Humoral; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009500:Neutralization Tests; D016036:Seroepidemiologic Studies; D012703:Serotyping; D019076:Transgenes; D055815:Young Adult
D057134:Antibodies, Neutralizing; D036022:Capsid Proteins; C485184:enhanced green fluorescent protein; C018315:hexon capsid protein, Adenovirus; D049452:Green Fluorescent Proteins