Seroprevalence of neutralizing antibodies to human adenoviruses type‐5 and type‐26 and chimpanzee adenovirus type‐68 in healthy Chinese adults

Zhang, Shujun; Huang, Wenxiang; Zhou, Xiangyang; Zhao, Qiquan; Wang, Qun; Jia, Bin

doi:10.1002/jmv.23546

Cited by 75 publications

(91 citation statements)

References 52 publications

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“…26 In addition, MN assays based on SEAP-expressing AdVs were reported to be more sensitive and objective than previously used CPE-based methods. 27 Consistent results were obtained when SEAP and EGFP reporter viruses were applied (Figure 1), reflecting the feasibility of these MN assays. Given that nAbs have shown beneficial effects for treating patients infected with H5N1 influenza virus or Ebola virus, 28, 29 these MN assays could be utilized to screen serums containing high levels of nAbs or monoclonal nAbs against Ad14 and Ad55, to treat patients with severe illnesses caused by these two AdVs (unpublished data).…”

Section: Discussionsupporting

confidence: 71%

Seroprevalence of neutralizing antibodies against adenovirus type 14 and 55 in healthy adults in Southern China

Zheng

Xiao

Feng

et al. 2017

Emerging Microbes & Infections

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Re-emerging human adenovirus types 14 (Ad14) and 55 (Ad55) have caused severe respiratory diseases and even deaths during recent outbreaks. However, the seroprevalence of neutralizing antibodies (nAbs) in healthy adults, which may reflect previous circulation and help to predict potential outbreaks, remains unclear. In this study, we established micro-neutralizing (MN) assays on the basis of recombinant Ad14 and Ad55 reporter viruses, and we investigated serum nAbs in healthy blood donors from Southern China. We found that the overall seropositive rates were 24.8% and 22.4% for Ad14 and Ad55 nAbs, respectively. The seropositive rates were low in individuals younger than 20, and they gradually increased with age. Ad55-seropositive individuals tended to have high nAb titers (>1000), while low (72–200) and moderate (201–1000) nAb levels were frequently observed in Ad14-seropositive ones. Surprisingly, the seropositive rates and nAb levels were associated with the blood type but not the gender of the blood donors, with type AB individuals displaying higher seropositive rates and nAb levels. Interestingly, a significant positive correlation was observed between Ad14 and Ad55 seroprevalence, and higher titers of nAbs were detected in double-positive individuals compared to single-positive ones. These results clarified the human humoral immune responses against Ad14 and Ad55 and revealed a low level of herd immunity in some subpopulations, which emphasized the importance of monitoring these two highly virulent adenoviruses and reinforced the development of prophylactic vaccines.

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Section: Discussionsupporting

confidence: 71%

Seroprevalence of neutralizing antibodies against adenovirus type 14 and 55 in healthy adults in Southern China

Zheng

Xiao

Feng

et al. 2017

Emerging Microbes & Infections

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“…Thus new rare adenovirus vectors with lower pre-existing immunity such as Ad26 and Ad35 are becoming more attractive (Holterman et al, 2004; Abbink et al, 2007; Barouch et al, 2012; Zhang et al, 2013), although these are relatively less immunogenic compared to Ad5 (Colloca et al, 2012). Besides the lower sero-prevalence, Ad26 neutralizing antibody titres are usually very low compared to Ad5 (Abbink et al, 2007; Chen et al, 2010; Mast et al, 2010).…”

Section: Non-replicating Recombinant Viral Vectorsmentioning

confidence: 99%

The influence of delivery vectors on HIV vaccine efficacy

Ondondo

2014

Front. Microbiol.

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Development of an effective HIV/AIDS vaccine remains a big challenge, largely due to the enormous HIV diversity which propels immune escape. Thus novel vaccine strategies are targeting multiple variants of conserved antibody and T cell epitopic regions which would incur a huge fitness cost to the virus in the event of mutational escape. Besides immunogen design, the delivery modality is critical for vaccine potency and efficacy, and should be carefully selected in order to not only maximize transgene expression, but to also enhance the immuno-stimulatory potential to activate innate and adaptive immune systems. To date, five HIV vaccine candidates have been evaluated for efficacy and protection from acquisition was only achieved in a small proportion of vaccinees in the RV144 study which used a canarypox vector for delivery. Conversely, in the STEP study (HVTN 502) where human adenovirus serotype 5 (Ad5) was used, strong immune responses were induced but vaccination was more associated with increased risk of HIV acquisition than protection in vaccinees with pre-existing Ad5 immunity. The possibility that pre-existing immunity to a highly promising delivery vector may alter the natural course of HIV to increase acquisition risk is quite worrisome and a huge setback for HIV vaccine development. Thus, HIV vaccine development efforts are now geared toward delivery platforms which attain superior immunogenicity while concurrently limiting potential catastrophic effects likely to arise from pre-existing immunity or vector-related immuno-modulation. However, it still remains unclear whether it is poor immunogenicity of HIV antigens or substandard immunological potency of the safer delivery vectors that has limited the success of HIV vaccines. This article discusses some of the promising delivery vectors to be harnessed for improved HIV vaccine efficacy.

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“…However, pre-existing neutralizing antibodies in humans have limited the clinical use of human adenoviral vectors 29 . As an alternative, chimpanzee adenoviruses have been extensively applied in vaccine development because their neutralizing antibodies are rare in humans 15, 29, 30 .…”

Section: Discussionmentioning

confidence: 99%

“…Chimpanzee adenovirus serotype 68 (AdC68) has been shown to be a good foreign gene carrier in both gene therapy and vaccine development owing to its high transduction efficiency, broad cell tropism, high gene expression, good genetic stability, and low seropositive rate in humans 14, 15 . Various vaccine candidates based on AdC68 have been developed for controlling many infectious diseases, including influenza 16–19 .…”

Section: Introductionmentioning

confidence: 99%

Both haemagglutinin-specific antibody and T cell responses induced by a chimpanzee adenoviral vaccine confer protection against influenza H7N9 viral challenge

Wang

Yuan

et al. 2017

Sci Rep

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Since 2013, the outbreak or sporadic infection of a new reassortant H7N9 influenza virus in China has resulted in hundreds of deaths and thousands of illnesses. An H7N9 vaccine is urgently needed, as a licensed human vaccine against H7N9 influenza is currently not available. Here, we developed a recombinant adenovirus-based vaccine, AdC68-H7HA, by cloning the H7N9 haemagglutinin (HA) gene into the chimpanzee adenoviral vector AdC68. The efficacy of AdC68-H7HA was evaluated in mice as well as guinea pigs. For comparison, an H7N9 DNA vaccine based on HA was also generated and tested in mice and guinea pigs. The results demonstrated that both AdC68-H7HA and the DNA vaccine prime-adenovirus boost regimen induced potent immune responses in animals and completely protected mice from lethal H7N9 influenza viral challenge. A post-immunization serum transfer experiment showed that antibody responses could completely protect against lethal challenge, while a T cell depletion experiment indicated that HA-specific CD8+ T cells responses also contributed to protection. Therefore, both HA-specific humoral immunity and cellular immunity play important roles in the protection. These data suggest that the chimpanzee adenovirus expressing HA is a promising vaccine candidate for H7N9 virus or other influenza viral subtypes.

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Seroprevalence of neutralizing antibodies to human adenoviruses type‐5 and type‐26 and chimpanzee adenovirus type‐68 in healthy Chinese adults

Cited by 75 publications

References 52 publications

Seroprevalence of neutralizing antibodies against adenovirus type 14 and 55 in healthy adults in Southern China

Seroprevalence of neutralizing antibodies against adenovirus type 14 and 55 in healthy adults in Southern China

The influence of delivery vectors on HIV vaccine efficacy

Both haemagglutinin-specific antibody and T cell responses induced by a chimpanzee adenoviral vaccine confer protection against influenza H7N9 viral challenge

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