Rare serotype adenoviral vectors for HIV vaccine development

Abstract

Human adenoviral vectors are being developed for use in candidate vaccines for HIV-1 and other pathogens. However, this approach suffered a setback when an HIV-1 vaccine using an adenovirus type 5 (Ad5) vector failed to reduce, and might even have increased, the rate of HIV infection in men who were uncircumcised and who had preexisting antibodies specific for Ad5. This increased interest in the evaluation of serologically distinct adenoviral vectors. In this issue of the JCI, Frahm and coworkers report evidence that preexisting cellular immune responses directed toward Ad5 reduce the immunogenicity of antigens expressed in Ad5-vectored vaccines and have cross-reacting potential with non-Ad5 adenoviral vectors. The implications of this observation need to be carefully evaluated in future clinical trials of all serotypes of adenovirus-vectored vaccines.

Figure 1. A framework for HIV vaccine development.

Two parallel pathways in an HIV vaccine development framework can be envisaged. One pathway (which leads to a regional vaccine strategy) builds on the poxvirus prime protein–subunit boost vaccine concept tested in the RV144 clinical trial (12). Such vaccines would test the ability of additional boosts and adjuvant formulations to improve the durability of protection observed in RV144 and evaluate performance in new risk and geographic populations. The second pathway (which would lead to a global vaccine strategy) seeks to evaluate universal or globally effective HIV vaccines using novel HIV vaccine types (including rare serotype human adenoviral vectors), insert design, adjuvants, and clinical study designs.