title: Circumventing antivector immunity by using adenovirus-infected blood cells for repeated application of adenovirus-vectored vaccines: proof of concept in rhesus macaques.
abstract: Adenovirus has been extensively exploited as a vector platform for delivering vaccines. However, preexisting antiadenovirus immunity is the major stumbling block for application of adenovirus-vectored vaccines. In this study, we found that freshly isolated peripheral blood mononuclear cells (PBMCs), mostly CD14(+) cells, from adenovirus serotype 5 (Ad5)-seropositive primates (humans and rhesus macaques) can be efficiently infected with Ad5 in vitro. On the basis of this observation, a novel strategy based on adenoviral vector-infected PBMC (AVIP) immunization was explored to circumvent antivector immunity. Autologous infusion of Ad5-SIVgag-infected PBMCs elicited a strong Gag-specific cellular immune response but induced weaker Ad5-neutralizing antibody (NAb) in Ad5-seronegative macaques than in macaques intramuscularly injected with Ad5-SIVgag. Moreover, Ad5-seropositive macaques receiving multiple AVIP immunizations with Ad5-SIVenv, Ad5-SIVgag, and Ad5-SIVpol vaccines elicited escalated Env-, Gag-, and Pol-specific immune responses after each immunization that were significantly greater than those in macaques intramuscularly injected with these Ad5-SIV vaccines. After challenged intravenously with a highly pathogenic SIVmac239 virus, macaques receiving AVIP immunization demonstrated a significant reduction in viral load at both the peak time and set-point period compared with macaques without Ad5-SIV vaccines. Our study warranted further research and development of the AVIP immunization as a platform for repeated applications of adenovirus-vectored vaccines.
authors.affiliation: State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
authors.forename: Caijun
authors.initials: C
authors.lastname: Sun
authors.forename: Liqiang
authors.initials: L
authors.lastname: Feng
authors.forename: Yinfeng
authors.initials: Y
authors.lastname: Zhang
authors.forename: Lijun
authors.initials: L
authors.lastname: Xiao
authors.forename: Weiqi
authors.initials: W
authors.lastname: Pan
authors.forename: Chufang
authors.initials: C
authors.lastname: Li
authors.forename: Linqi
authors.initials: L
authors.lastname: Zhang
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
mesh_terms: D000256:Adenoviridae / Q000276:immunology*; D062705:Adenovirus Vaccines; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D015686:Gene Products, env / Q000276:immunology; D015683:Gene Products, gag / Q000276:immunology; D015684:Gene Products, pol / Q000276:immunology; D005822:Genetic Vectors; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D008253:Macaca mulatta; D018449:SAIDS Vaccines / Q000235:genetics* / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology
chemical_list: D062705:Adenovirus Vaccines; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D015686:Gene Products, env; D015683:Gene Products, gag; D015684:Gene Products, pol; D018950:Lipopolysaccharide Receptors; D018449:SAIDS Vaccines; D014765:Viral Vaccines