Prevalence of serum neutralizing antibodies to adenovirus type 5 (Ad5) and 41 (Ad41) in children is associated with age and sanitary conditions

Wei-xiong, Yang; Zou, Xiaohui; Jiang, Shuang-Ying; Lu, Nan-Nan; Han, Mei; Jun, Zhao; Guo, Xiaojuan; Zhao, Shouqin; Zhang, Lu

doi:10.1016/j.vaccine.2016.09.043

Cited by 22 publications

(26 citation statements)

References 42 publications

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“…Similar distributions in seropositive rates and nAb titers of HAdV-4 or HAdV-5 between gender groups were observed (Fig. 3 ), in accordance with the results observed for other adenovirus types 4 , 29 . These results suggest that the sensitivity of men and women to infection by HAdV-4 or HAdV-5 was consistent and that the same level of nAbs could be generated by males and females after infection with HAdV-4 or HAdV-5.…”

Section: Discussionsupporting

confidence: 89%

“…The prevalence of HAdV-4 and HAdV-5 nAbs varied by geographic location and appeared to be significantly higher in West Africa than in China and in Jiangsu than in Beijing, the capital city of China. Geographical differences have also been observed in other epidemiological studies of HAdV-4 and HAdV-5 21 , 22 , 24 , 25 , and these variations may be attributable to climate (higher nAbs among populations who have spent a great deal of time in tropical regions), crowding (high-population density may facilitate transmission), or sanitary conditions 12 , 15 , 22 , 29 . Thus, these results revealed a greater risk of adenovirus infection in developing countries due to heat, crowding, and poor sanitation.…”

Section: Discussionmentioning

confidence: 67%

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Seroepidemiological investigation of HAdV-4 infection among healthy adults in China and in Sierra Leone, West Africa

Wang¹,

Li²,

Wu³

et al. 2018

Emerging Microbes & Infections

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An apparent increase in the frequency of human adenovirus type 4 (HAdV-4) infections among general populations has been observed over the past 10 years. However, available epidemiological data that may reflect previous viral circulation and assist in predicting potential outbreaks are sparse, particularly in mainland China and Africa. In this study, a convenient neutralization assay for use in the surveillance of historical HAdV-4 infections was established based on a recombinant luciferase-expressing virus. Subsequently, the neutralizing antibodies (nAbs) of 1013 healthy adult serum samples from China and Sierra Leone were evaluated. Our results showed that over 50% of the participants from China and nearly 70% of donors from Sierra Leone had detectable nAbs against HAdV-4 despite the few infection cases officially reported in these regions. Furthermore, the prevalence of nAbs to HAdV-4 is lower than that to HAdV-5, and both varied by geographic location. In addition, the seropositive rates of both HAdV-4 and HAdV-5 nAbs increased with age. However, the nAbs stimulated by HAdV-4 remained stable at low (≤200) levels among the different age groups, whereas moderate (201–1000) or high (>1000) nAb levels were produced by HAdV-5 and tended to decrease with age. These results elucidate the human humoral immune response against HAdV-4 and revealed that this virus may be an underestimated causative agent of respiratory disease among adults in China and West Africa, demonstrating the importance of HAdV-4 surveillance and providing useful insights for the future development of HAdV-4-based vaccines.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 67%

Seroepidemiological investigation of HAdV-4 infection among healthy adults in China and in Sierra Leone, West Africa

Wang¹,

Li²,

Wu³

et al. 2018

Emerging Microbes & Infections

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“…The arguments used for HAdV-E4-based vaccines were its biological properties and respiratory tropism. HAdV-F41 showed high seroprevalence worldwide according to the handful of studies performed on US, European, and Asian samples, reaching a maximum of 95% for healthy children from south China [138]. It is also clear that reporting HAdVs seroprevalence in populations from vast and diversified countries (in terms of climates, populations and densities) such as the United States, China, or Brazil can poorly reflect the likely diversity.…”

Section: Moving Forwardmentioning

confidence: 99%

A review of 65 years of human adenovirus seroprevalence

Mennechet

Paris

Ouoba

et al. 2019

Expert Review of Vaccines

132

135

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Introduction: Human adenovirus (HAdV)-derived vectors have been used in numerous pre-clinical and clinical trials during the last 40 years. Current research in HAdV-based vaccines focuses on improving transgene immunogenicity and safety. Because pre-existing humoral immunity against HAdV types correlate with reduced vaccine efficacy and safety, many groups are exploring the development of HAdV types vectors with lower seroprevalence. However, global seroepidemiological data are incomplete. Areas covered: The goal of this review is to centralize 65 years of research on (primarily) HAdV epidemiology. After briefly addressing adenovirus biology, we chronical HAdV seroprevalence studies and highlight major milestones. Finally, we analyze data from about 50 studies with respect to HAdVs types that are currently used in the clinic, or are in the developmental pipeline. Expert opinion: Vaccination is among the most efficient tools to prevent infectious disease. HAdVbased vaccines have undeniable potential, but optimization is needed and antivector immunity remains a challenge if the same vectors are to be administrated to different populations. Here, we identify gaps in our knowledge and the need for updated worldwide epidemiological data.

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“…However, inbred rats housed in a barrier facility are unlikely to have been exposed to this specific virus. In contrast, most humans have been exposed to adenovirus 5 and, therefore, have already raised system-neutralizing antibodies against the virus, 44,45 which could exacerbate the immune response to HDAd5 and potentially decrease the transduction efficiency due to the clearance of HDAd5-infected cells. Although we observed robust HDAd5-mediated eGFP fluorescence within the RPE and throughout the neural retina, the observed transduction was patchy, and we did not quantify the transduction efficiency in distinct layers of the retina.…”

Section: Discussionmentioning

confidence: 99%

Helper-Dependent Adenovirus Transduces the Human and Rat Retina but Elicits an Inflammatory Reaction When Delivered Subretinally in Rats

et al. 2019

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The identification of >100 genes causing inherited retinal degeneration and the promising results of recent gene augmentation trials have led to an increase in the number of studies investigating the preclinical efficacy of viral-mediated gene transfer. Despite success using adeno-associated viruses, many disease-causing genes, such as ABCA4 or USH2A, are too large to fit into these vectors. One option for large gene delivery is the family of integration-deficient helper-dependent adenoviruses (HDAds), which efficiently transduce postmitotic neurons. However, HDAds have been shown in other organ systems to elicit an immune response, and the immunogenicity of HDAds in the retina has not been characterized. In this study, HDAd serotype 5 (HDAd5) was found to successfully transduce rod and cone photoreceptors in ex vivo human retinal organ cultures. The ocular inflammatory response to subretinal injection of the HDAd5 was evaluated using a rat model. Subretinal injection of HDAd5 carrying cytomegalovirus promoter-driven enhanced green fluorescent protein (HDAd5-CMVp-eGFP) elicited a robust inflammatory response by 3 days postinjection. This reaction included vitreous infiltration of ionized calcium-binding adapter molecule 1 (Iba1)-positive monocytes and increased expression of the proinflammatory protein, intercellular adhesion molecule 1 (ICAM-1). By 7 days postinjection, most Iba1-positive infiltrates migrated into the neural retina and ICAM-1 expression was significantly increased compared with buffer-injected control eyes. At 14 days postinjection, Iba1-positive cells persisted in the retinas of HDAd5-injected eyes, and there was thinning of the outer nuclear layer. Subretinal injection of an empty HDAd5 virus was used to confirm that the inflammatory response was in response to the HDAd5 vector and not due to eGFP-induced overexpression cytotoxicity. Subretinal injection of lower doses of HDAd5 dampened the inflammatory response, but also eGFP expression. Despite their larger carrying capacity, further work is needed to elucidate the inflammatory pathways involved and to identify an immunomodulation paradigm sufficient for safe and effective transfer of large genes to the retina using HDAd5.

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Prevalence of serum neutralizing antibodies to adenovirus type 5 (Ad5) and 41 (Ad41) in children is associated with age and sanitary conditions

Cited by 22 publications

References 42 publications

Seroepidemiological investigation of HAdV-4 infection among healthy adults in China and in Sierra Leone, West Africa

Seroepidemiological investigation of HAdV-4 infection among healthy adults in China and in Sierra Leone, West Africa

A review of 65 years of human adenovirus seroprevalence

Helper-Dependent Adenovirus Transduces the Human and Rat Retina but Elicits an Inflammatory Reaction When Delivered Subretinally in Rats

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