Elicitation of immunity to HIV type 1 Gag is determined by Gag structure

The gag gene of the human immunodeficiency virus type 1 (HIV-1) encodes for viral proteins that self-assemble into viral particles. The primary Gag gene products (capsid, matrix, and nucleocapsid) elicit humoral and cellular immune responses during natural infection, and these proteins are included in many preclinical and clinical HIV/AIDS vaccines. However, the structure (particulate or soluble) of these proteins may influence the immunity elicited during vaccination. In this study, mice were inoculated with four different HIV-1 Gag vaccines to compare the elicitation of immune responses by the same Gag immunogen presented to the immune system in different forms. The immunity elicited by particles produced in vivo by DNA plasmid (pGag) was compared to these same proteins retained intracellularly (pGag(DMyr)). In addition, the elicitation of anti- Gag immunity by Gag(p55) virus-like particles (VLPs) or soluble, nonparticulate Gag(p55) proteins was compared. Enhanced cellular responses, but almost no anti-Gag antibodies, were elicited with intracellularly retained Gag proteins. In contrast, DNA vaccines expressing VLPs elicited both anti-Gag antibodies and cellular responses. Mice vaccinated with purified Gag(p55) VLPs elicited robust humoral and cellular immune responses, which were significantly higher than the immunity elicited by soluble, nonparticulate Gag(p55) protein. Overall, purified particles of Gag effectively elicited the broadest and highest titers of anti-Gag immunity. The structural form of Gag influences the elicited immune responses and should be considered in the design of HIV/AIDS vaccines.