Epidemiology of adenovirus type 5 neutralizing antibodies in healthy people and AIDS patients in Guangzhou, southern China

Sun, Caijun; Zhang, Yinfeng; Feng, Liqiang; Pan, Weiqi; Zhang, Maochao; Hong, Zhe-yu; Ma, Xin; Chen, Xiaoping; Chen, Ling

doi:10.1016/j.vaccine.2011.03.042

Cited by 58 publications

(67 citation statements)

References 23 publications

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“…For Ad5-based vaccines, PEI to the vector is an issue of concern (19). In order to analyze the immunogenicity of Ad5-PAopt in the presence of PEI to the Ad5 vector, BALB/c mice were intramuscularly or intranasally inoculated without (controls) or with 10 10 viral particles of Ad5-EGFP and maintained for 10 weeks.…”

Section: Resultsmentioning

confidence: 99%

Intramuscular Delivery of Adenovirus Serotype 5 Vector Expressing Humanized Protective Antigen Induces Rapid Protection against Anthrax That May Bypass Intranasally Originated Preexisting Adenovirus Immunity

Zhang

et al. 2013

Clin. Vaccine Immunol.

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Developing an effective anthrax vaccine that can induce a rapid and sustained immune response is a priority for the prevention of bioterrorism-associated anthrax infection. Here, we developed a recombinant replication-deficient adenovirus serotype 5-based vaccine expressing the humanized protective antigen (Ad5-PAopt). A single intramuscular injection of Ad5-PAopt resulted in rapid and robust humoral and cellular immune responses in Fisher 344 rats. Animals intramuscularly inoculated with a single dose of 10 8 infectious units of Ad5-PAopt achieved 100% protection from challenge with 10 times the 50% lethal dose (LD 50 ) of anthrax lethal toxin 7 days after vaccination. Although preexisting intranasally induced immunity to Ad5 slightly weakened the humoral and cellular immune responses to Ad5-PAopt via intramuscular inoculation, 100% protection was achieved 15 days after vaccination in Fisher 344 rats. The protective efficacy conferred by intramuscular vaccination in the presence of preexisting intranasally induced immunity was significantly better than that of intranasal delivery of Ad5-PAopt and intramuscular injection with recombinant PA and aluminum adjuvant without preexisting immunity. As natural Ad5 infection often occurs via the mucosal route, the work here largely illuminates that intramuscular inoculation with Ad5-PAopt can overcome the negative effects of immunity induced by prior adenovirus infection and represents an efficient approach for protecting against emerging anthrax.

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Section: Resultsmentioning

confidence: 99%

Intramuscular Delivery of Adenovirus Serotype 5 Vector Expressing Humanized Protective Antigen Induces Rapid Protection against Anthrax That May Bypass Intranasally Originated Preexisting Adenovirus Immunity

Zhang

et al. 2013

Clin. Vaccine Immunol.

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“…Specific Ad5 NAb titers were measured as previously reported (2), with our minor modifications (54). Briefly, 293 cells were seeded at 3 ϫ 10 4 cells per well in 96-well plates 1 to 2 days before the assay so that the cells were able to reach 95 to 100% confluence.…”

Section: Methodsmentioning

confidence: 99%

“…On the other hand, there is a higher prevalence of preexisting anti-Ad5 immunity in populations of the developing countries (42,54,57), and so the implication of this modality is even more significant. We believe that if this modality can achieve positive results in the future human clinical trials in any countries willing to shed light on HIV vaccines or any infectious diseases with currently no efficacious vaccines, it will attract support for resources to develop a simple and user-friendly device to enable its application.…”

Section: Cd14mentioning

confidence: 99%

“…Although it is still a puzzle regarding what constitutes an effective immune responses that can confer effective protection for an HIV vaccine (21,29,34,39), stimulation of robust and balanced cellular and humoral responses targeted to HIV antigens has been considered to be the necessary pieces if an HIV vaccine will be effective in humans (5,6,20,25,46). However, it has been reported that approximately 40% of the adult population in America (42), 77% of the total population in Guangzhou, southern China (54), and more than 93% of the children in Sub-Saharan Africa (57) are Ad5 seropositive. Therefore, improving the immunogenicity of Ad-vectored vaccines in the Ad5-seropositive population and minimizing as well as circumventing host immune responses to Ad5 will be of great significance.…”

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confidence: 99%

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Circumventing Antivector Immunity by Using Adenovirus-Infected Blood Cells for Repeated Application of Adenovirus-Vectored Vaccines: Proof of Concept in Rhesus Macaques

Sun

Feng

Zhang

et al. 2012

J Virol

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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.

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“…Moreover, pre-existing anti-Adv neutralizing antibodies in a large population of people worldwide, especially anti-Ad5 antibodies, is a barrier for Adv-mediated clinical applications. [11][12][13] In addition, Adv are limited to local administration due to substantial liver tropism and subsequent severe hepatotoxicity after systemic administration.…”

Section: Introductionmentioning

confidence: 99%

Protection of adenovirus from neutralizing antibody by cationic PEG derivative ionically linked to adenovirus

Zeng¹,

Han²,

Zhao³

et al. 2012

IJN

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Background:The generation of anti-adenovirus neutralizing antibody (NAb) in humans severely restricts the utilization of recombinant adenovirus serotype 5 (Ad5) vectors in gene therapy for a wide range of clinical trials. To overcome this limitation, we ionically complexed Ad5 with a newly synthesized copolymer, which we called APC, making an adenovirus shielded from NAb. Methods: APC, a cationic polyethylene glycol derivative, was synthesized via two steps of ring-opening copolymerization of ethylene oxide and allyl glycidyl ether, followed by the addition of 2-mercaptoethylamine. The copolymer or the control PEI-2k was ionically complexed to anionic Ad5 in 5% glucose, and in vitro transduction assays were carried out in coxsackievirus and adenovirus receptor-positive cells (A549) and coxsackievirus and adenovirus receptornegative cells (B16 and SKOV3). The physical properties and morphology of adenovirus alone or the complexes were investigated respectively by zeta potential, size distribution, and transmission electron microscopy image. Then cytotoxicity of APC was examined using 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide assays. Finally, the ability of APC to protect adenovirus from NAb was evaluated by transfection assays after a neutralizing effect. Results: APC was successfully synthesized and showed a low cytotoxicity. Positively charged Ad5/APC exhibited slightly increased diameter (130.2 ± 0.60 nm) than naked Ad5 (115.6 ± 5.46 nm) while Ad5/PEI-2k showed severe aggregation (1382 ± 79.9 nm). Ad5/APC achieved a gene transfection level as high as Ad5/PEI-2k in A549 or B16 cells, and significantly higher than Ad5/PEI-2k in SKOV3 cells. Most importantly, after the exposure to the neutralizing antibody, naked Ad5 and Ad5/PEI-2k exhibited poor gene expression while Ad5/APC still showed significantly efficient gene expression. Conclusion: Our results demonstrated that Ad5/APC complex offered good protection for Ad5 against NAb in vitro and suggested a potential strategy of resistance to NAb in vivo.

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Epidemiology of adenovirus type 5 neutralizing antibodies in healthy people and AIDS patients in Guangzhou, southern China

Cited by 58 publications

References 23 publications

Intramuscular Delivery of Adenovirus Serotype 5 Vector Expressing Humanized Protective Antigen Induces Rapid Protection against Anthrax That May Bypass Intranasally Originated Preexisting Adenovirus Immunity

Intramuscular Delivery of Adenovirus Serotype 5 Vector Expressing Humanized Protective Antigen Induces Rapid Protection against Anthrax That May Bypass Intranasally Originated Preexisting Adenovirus Immunity

Circumventing Antivector Immunity by Using Adenovirus-Infected Blood Cells for Repeated Application of Adenovirus-Vectored Vaccines: Proof of Concept in Rhesus Macaques

Protection of adenovirus from neutralizing antibody by cationic PEG derivative ionically linked to adenovirus

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