Seroprevalence of neutralizing antibodies against adenovirus type 26 and 35 in healthy populations from Guangdong and Shandong provinces, China.

Human adenoviruses type 26 (HAdV26) and type 35 (HAdV35) have increasingly become the choice of adenovirus vectors for vaccine application. However, the population pre-existing immunity to these two adenoviruses in China, which may reduce vaccine efficacy, remains largely unknown. Here, we established micro-neutralizing (MN) assays to investigate the seroprevalence of neutralizing antibodies (nAbs) against HAdV26 and HAdV35 in the general population of Guangdong and Shandong provinces, China. A total of 1184 serum samples were collected, 47.0% and 15.8% of which showed HAdV26 and HAdV35 nAb activity, respectively. HAdV26-seropositive individuals tended to have more moderate nAbs titers (201-1000), while HAdV35-seropositive individuals appeared to have more low nAbs titers (72-200). The seropositive rates of HAdV26 and HAdV35 in individuals younger than 20 years old were very low. The seropositive rates of HAdV26 increased with age before 70 years old and decreased thereafter, while HAdV35 seropositive rates did not show similar characteristics. Notably, the seropositive rates and nAb levels of both HAdV26 and HAdV35 were higher in Guangdong Province than in Shandong Province, but did not exert significant differences between males and females. The seroprevalence between HAdV26 and HAdV35 showed little correlation, and no significant cross-neutralizing activity was detected. These results clarified the characteristics of the herd immunity against HAdV26 and HAdV35, and provided information for the rational development and application of HAdV26 and HAdV35 as vaccine vectors in China.

Functional properties of DENV EDIII­reactive antibodies in human DENV­1­infected sera and rabbit antiserum to EDIII.

The envelope domain III (EDIII) of the dengue virus (DENV) has been confirmed to be involved in receptor binding. It is the target of specific neutralizing antibodies, and is considered to be a promising subunit dengue vaccine candidate. However, several recent studies have shown that anti­EDIII antibodies contribute little to the neutralizing or enhancing ability of human DENV­infected serum. The present study involved an analysis of the neutralization and antibody­dependent enhancement (ADE) activities of EDIII­reactive antibodies in human convalescent sera from patients with primary DENV­1 infection and rabbit antiserum immunized with recombinant DENV­1 EDIII protein. The results indicated that serum neutralization was not associated with titres of EDIII­binding antibodies in the human DENV­1­infected sera. The depletion of anti­EDIII antibodies from these serum samples revealed that the anti­EDIII antibodies of the patients contributed little to neutralization and ADE. However, the EDIII­reactive antibodies from the rabbit antiserum exhibited protective abilities of neutralization at a high dilution (~1:50,000) and ADE at a low dilution (~1:5,000) for the homotypic DENV infection. Notably, the rabbit antiserum displayed ADE activity only at a dilution of 1:40 for the heterotypic virus infection, which suggests that EDIII­reactive antibodies may be safe in secondary infection with heterotypic viruses. These results suggest that DENV EDIII is not the predominant antigen of the DENV infection process; however, purified or recombinant DENV EDIII may be used as a subunit vaccine to provoke an effective and safe antibody response.