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140 Induction of Efficacious Immune Responses Using Heterologous Prime: Boost Regimens of Recombinant DNA and MVA Vectored HIV Vaccines and GM-CSF as the Adjuvant

Newman, Mark J1; Robinson, Harriet L1; Lai, Lilin2; Chennareddi, Lakshmi2; Kwa, Suefen2; Villinger, Francois2; Montefiori, David3; Kozlowski, Pamela4; Wyatt, Linda S5; Earl, Patricia5; Moss, Bernard5; Amara, Rama Rao2

JAIDS Journal of Acquired Immune Deficiency Syndromes: April 2011 - Volume 56 - Issue - p 57
doi: 10.1097/01.qai.0000397326.26622.15

1GeoVax Inc., Smyrna, GA; 2Yerkes National Primate Research Center, Atlanta, GA; 3Duke University Medical Center, Durham, NC; 4Louisiana State University Health Sciences Center, New Orleans, LA; and 5National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD

The GeoVax DNA and MVA-vectored HIV vaccines are single recombinant moieties designed to express non-infectious, immature virus-like-particles bearing “native” Env protein. The DNA vaccines encode Gag, Pol and Env using HIV subgenomic splicing, with or without GM-CSF in the nef region, while the MVA vectored vaccines encode Gag, Pol and Env under the control of the mH5 early/late vaccinia promoter. This vaccine design was tested using the rhesus macaque model and SIV-239 prototype vaccines encoding the analogous SIV structural proteins, with and without GM-CSF. A heterologous (DNA + MVA) vaccination regimen was employed with standard immune response measurements and efficacy testing using weekly intra-rectal heterologous infectious challenges with SIV-E660 (MID40). Comparable cellular immune responses were induced. However, the GM-CSF-supplemented vaccine induced antibodies specific to SIV gp160 with higher binding avidity to the “native” protein and higher neutralization titers specific for a tier 1 variant of E660 (E660.11). The GM-CSF supplemented vaccine also induced a higher level of efficacy with 70% (5/7) of the animals protected against 12 challenges; compared to a 25% (2/8) level of efficacy obtained using the unadjuvanted vaccine. The use of the MVA vectored SIV vaccine alone, without GM-CSF, induced higher titers of antibodies specific to SIV gp160 and reduced cellular responses. The level of protection was comparable, if not better, to that obtained using the unadjuvanted DNA + MVA products.

In a completed Phase 1 (HVTN-065) clinical trial, similar immune response patterns were observed with the administration of the MVA vectored vaccine alone resulting in higher titers of antibodies while the use of the heterologous prime-boost regimen DNA + MVA induced higher CD4+ T cell responses and lower antibody titers. The unadjuvanted HIV vaccines are currently being tested in a Phase 2 trial (HVTN-205) while the GM-CSF supplemented vaccine represents the next generation product in the GeoVax pipeline.

Copyright © 2011 Wolters Kluwer Health, Inc. All rights reserved.