![Sample our Bioscience journals, sign in here to start your access, Latest two full volumes FREE to you for 14 days]({"type":"image" , "src" : "/sda/5925/TOC-Subject-Sample-2021-Bioscience.jpg"})
Abstract
The induction of a balanced immune response targeting the major structural proteins, Gag and Env of HIV, is important for the development of an efficacious vaccine. The use of DNA plasmids expressing different antigens offers the opportunity to test in a controlled manner the influence of different vaccine components on the magnitude and distribution of the vaccine-induced cellular and humoral immune responses. Here, we show that increasing amounts of env DNA results in greatly enhanced Env antibody titers without significantly affecting the levels of anti-Env cellular immune responses. Co-immunization with Env protein further increased antibody levels, indicating that vaccination with DNA only is not sufficient for eliciting maximal humoral responses against Env. In contrast, under high env:gag DNA plasmid ratio, the development of Gag cellular responses was significantly reduced by either SIV or HIV Env, whereas Gag humoral responses were not affected. Our data indicate that a balanced ratio of the 2 key HIV/SIV vaccine components, Gag and Env, is important to avoid immunological interference and to achieve both maximal humoral responses against Env to prevent virus acquisition and maximal cytotoxic T cell responses against Gag to prevent virus spread.
Disclosure of Potential Conflicts of Interest
GNP and BKF are inventors on US Government-owned patents and patent applications related to DNA vaccines and gene expression optimization. SR is a founder and shareholder in Immune Design Corp., which has certain rights to the adjuvant used in this study under license agreement with IDRI. NYS is a full time employee of Inovio Pharmaceuticals and as such receives compensation in the form of salary and stock options. There are no further patents, products in development or marketed products to declare.
Acknowledgments
We thank D Weiss, J Treece, I. Kalisz and the staff at Advanced Bioscience Laboratory for excellent support, J. Bear and B. Chowdhury for technical support, and T. Jones for editorial assistance. The following reagent was obtained through the NIH AIDS Reagent Program, Division of AIDS, NIAID, NIH: HIV-1 PTE Env Peptides (Cat #11551).
Funding
This work was supported in part by the Intramural Research Program of the National Cancer Institute, National Institutes of Health (NCI/NIH) (BKF, GNP), and Bill and Melinda Gates Foundation Grant #42387 (SGR).
