Abstract
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.
Highlights
Human adenoviruses (AdVs) are non-enveloped, double-stranded DNA viruses belonging to Adenoviridae.[1]
Establishment and validation of MN assays based on recombinant Ad14 and Ad55 reporter viruses To generate replication-competent reporter viruses, the E3 regions of Ad14 and Ad55 were depleted, and the expression cassettes for EGFPor secreted alkaline phosphatase (SEAP) were inserted (Figure 1A)
The results showed that serums with neutralizing antibodies (nAbs) titers o72 displayed no detectable inhibition in relation to Ad14-enhanced green fluorescent protein (EGFP) or Ad55-EGFP infection for all the dilutions, while those with nAb titers 472 exhibited various neutralizing activities, which was consistent with the titers that were determined by SEAP activity (Figures 1B and 1C)
Summary
Human adenoviruses (AdVs) are non-enveloped, double-stranded DNA viruses belonging to Adenoviridae.[1]. A newly emergent variant of Ad14, which was designated Ad14p1, has caused several outbreaks of acute febrile respiratory illness globally since 2006.11–15 High rates of severe illness and even deaths were reported following these outbreaks.[13,14,15] Ad55, an inter-typic recombinant of
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