Abstract
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.
Highlights
Human adenoviruses (HAdVs) are nonenveloped, double-stranded DNA viruses belonging to the Adenoviridae family
Serial dilutions of the human adenovirus type 4 (HAdV-4)-positive serum samples were incubated with a fixed amount of a recombinant replicationcompetent HAdV-4-luciferase (Ad4-Luc) at three infectious units (IFU)/cell ratios (0.5, 1, and 1.5) to calculate serum titers
According to previous epidemiological and clinical studies of HAdV-4 infection among US military trainees, HAdV-4 specific neutralizing antibodies (nAbs) were observed in 97% of the recruits naturally infected with the HAdV-4 virus, and HAdV-4 could be isolated from 92% of the patients with increased HAdV-4 specific nAbs[12]
Summary
Human adenoviruses (HAdVs) are nonenveloped, double-stranded DNA viruses belonging to the Adenoviridae family. HAdV species B (HAdV-B3, B7, B21, and B55) and C (HAdV-C1, C2, C5, and C6) are the most common viruses responsible for severe respiratory infections worldwide[1,5,6,7,8,9,10,11]. HAdV-4, the only member of human adenovirus species E, has been a significant cause of acute respiratory disease in the US military recruits since its identification in the 1950s12. The high susceptibility to HAdV-4 infection and the high communicability among incoming recruits during basic training might be attributable to the low level of pre-existing immunity in these individuals as well as the closed and crowded conditions in barracks[12].
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