Development of a novel simian adenovirus 24 based vaccine vector

Background

Human adenovirus serotype 5 is a potent vaccine vector, but its use has been hampered by high seroprevalence amongst people in sub-Sahara Africa. Novel adenoviral vaccine vectors from strains with lower seroprevalence worldwide are being developed that can evade pre-existing immunity. Here we describe the development of a simian Ad24 (sAd24)-based vaccine vector.

Methods

Neutralizing antibodies against sAd24 were determined using a panel of 106 rhesus macaque sera and 128 human sera from Rwanda and South Africa using a luciferase-based adenovirus neutralization assay.

The immunogenicity of a single dose of 10E7, 10E8 or 10E9 virus particles of sAd24-SIV Gag based vector was determined in C57BL/6 mice. SIV-Gag-specific immune responses were assessed by Db/AL11 tetramer binding assays, IFN-γ ELISPOT assays and ICS assays.

Results

Neutralizing antibodies were found in 7% of monkeys, all with titers <200. In humans from sub-Saharan Africa, 45% was positive for sAd24 neutralizing antibodies, but titers remained low and 90% had titers <200. In comparison, seroprevalence of Ad5 in sub-Saharan Africa is 86.4-89.5% with 61.1-78.7% of this population showing titers >200 and 25.1-46.8% showing titers >1000. Gag specific cellular immune responses elicited by sAd24-SIV Gag in mice are comparable to those seen with the human Ad26 and Ad28 vectors currently in development.

Conclusion

These data suggest that sAd24 is promising for further studies as a candidate vaccine vector.