Co-immunization of DNA and Protein in the Same Anatomical Sites Induces Superior Protective Immune Responses against SHIV Challenge.

We compare immunogenicity and protective efficacy of an HIV vaccine comprised of env and gag DNA and Env (Envelope) proteins by co-administration of the vaccine components in the same muscles or by separate administration of DNA + protein in contralateral sites in female rhesus macaques. The 6-valent vaccine includes gp145 Env DNAs, representing six sequentially isolated Envs from the HIV-infected individual CH505, and matching GLA-SE-adjuvanted gp120 Env proteins. Interestingly, only macaques in the co-administration vaccine group are protected against SHIV CH505 acquisition after repeated low-dose intravaginal challenge and show 67% risk reduction per exposure. Macaques in the co-administration group develop higher Env-specific humoral and cellular immune responses. Non-neutralizing Env antibodies, ADCC, and antibodies binding to FcγRIIIa are associated with decreased transmission risk. These data suggest that simultaneous recognition, processing, and presentation of DNA + Env protein in the same draining lymph nodes play a critical role in the development of protective immunity.
Competing Interests: Declaration of Interests G.N.P. and B.K.F. are inventors on US Government-owned patents related to DNA vaccines and gene expression optimization. B.F.H. has submitted patent applications covering the Envs used in this study. S.G.R. is a full-time employee of Infectious Disease Research Institute and as such receives compensation in the form of salary. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The manuscript has been reviewed by the Walter Reed Army Institute of Research. There is no objection to its presentation and/or publication. The opinions or assertions contained herein are the private views of the author, and are not to be construed as official, or as reflecting true views of the Department of the Army or the Department of Defense. The views expressed in this article are those of the authors and do not necessarily reflect the official policy of the Department of the Army, Department of Defense, or the U.S. Government. The other authors declare no competing interests. This work was produced solely by the authors and that no other individuals or entities influenced any aspects of the work.
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