TY - JOUR
T1 - Safety and immunogenicity of PENNVAX-G DNA prime administered by biojector 2000 or CELLECTRA electroporation device with modified vaccinia Ankara-CMDR boost
AU - Ake, Julie A.
AU - Schuetz, Alexandra
AU - Pegu, Poonam
AU - Wieczorek, Lindsay
AU - Eller, Michael A.
AU - Kibuuka, Hannah
AU - Sawe, Fredrick
AU - Maboko, Leonard
AU - Polonis, Victoria
AU - Karasavva, Nicos
AU - Weiner, David
AU - Sekiziyivu, Arthur
AU - Kosgei, Josphat
AU - Missanga, Marco
AU - Kroidl, Arne
AU - Mann, Philipp
AU - Ratto-Kim, Silvia
AU - Eller, Leigh Anne
AU - Earl, Patricia
AU - Moss, Bernard
AU - Dorsey-Spitz, Julie
AU - Milazzo, Mark
AU - Ouedraogo, G. Laissa
AU - Rizvi, Farrukh
AU - Yan, Jian
AU - Khan, Amir S.
AU - Peel, Sheila
AU - Sardesai, Niranjan Y.
AU - Michael, Nelson L.
AU - Ngauy, Viseth
AU - Marovich, Mary
AU - Robb, Merlin L.
N1 - Funding Information:
Financial support. This work was supported by the Department of Defense through cooperative agreements (W81XWH-07-2-0067 and W81XWH-11–0174) with the Henry M. Jackson Foundation for the Advancement of Military Medicine and by the NIAID through an interagency agreement with the US Army Medical Research and Materiel Command (Y1-AI-2642-17). N. Y. S., A. S. K., J. Y., and D. B. W. gratefully acknowledge funding support for HIV vaccine development from NIH/NIAID/Division of AIDS under an HIV Vaccine Design and Development Team contract awarded to Inovio Pharmaceuticals (HHSN272200800063C).
Funding Information:
Acknowledgments. We thank the RV262 study participants and study teams in the United States, Uganda, Tanzania, and Kenya for their contribution to the conduct of the study; Safety Monitoring Committee members, led by Chair Dr Eric Sandstrom, for their commitment to volunteer safety; US Military HIV Research Program and Armed Forces Research Institute of Medical Sciences immunomonitoring laboratory technicians for their production of immunogenicity data; Dr Michael Pensiero, Ms Tina Tong, Dr Elizabeth Adams, Dr Ana Martinez, Dr Phillip Renzullo of the Division of AIDS/National Institute of Allerfy and Infectious Diseases (NIAID) and COL (Dr) Robert O’Connell, and Dr Mark de Souza of AFRIMS for their expert support and contributions to study design and conduct.
Funding Information:
Correspondence: J. A. Ake, MD, MSc, FACP, Principal Deputy Director, U.S. Military HIV Research Program, Walter Reed Army Institute of Research, 503 Robert Grant Ave., Silver Spring, MD 20910 (jake@hivresearch.org). The Journal of Infectious Diseases® 2017;216:1080–90 Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US. DOI: 10.1093/infdis/jix456
Funding Information:
1US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, 2Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, 3Laboratory of Viral Diseases, and 4Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and 5Military Infectious Diseases Research Program, Ft. Detrick, Maryland; 6Armed Forces Research Institute of Medical Sciences, Department of Retrovirology, Bangkok, Thailand; 7Makerere University/Walter Reed Project, Kampala, Uganda; 8KEMRI/Walter Reed Project, Kericho, Kenya; 9National Institute of Medical Research, Mbeya Medical Research Centre, Mbeya, United Republic of Tanzania; 10Wistar Institute, Philadelphia, and 11Inovio Pharmaceuticals, Inc, Plymouth Meeting, Pennsylvania; and 12Division of Infectious Diseases and Tropical Medicine, Medical Center of the University of Munich, Germany
Funding Information:
This work was supported by the Department of Defense through cooperative agreements (W81XWH-07-2-0067 and W81XWH-11-0174) with the Henry M. Jackson Foundation for the Advancement of Military Medicine and by the NIAID through an interagency agreement with the US Army Medical Research and Materiel Command (Y1-AI-2642-17). N. Y. S., A. S. K., J. Y., and D. B. W. gratefully acknowledge funding support for HIV vaccine development from NIH/NIAID/Division of AIDS under an HIV Vaccine Design and Development Team contract awarded to Inovio Pharmaceuticals (HHSN272200800063C).
Publisher Copyright:
© 2017 Oxford University Press. All rights reserved.
PY - 2017/11/1
Y1 - 2017/11/1
N2 - Background. We report the first-in-human safety and immunogenicity evaluation of PENNVAX-G DNA/modified vaccinia Ankara-Chiang Mai double recombinant (MVA-CMDR) prime-boost human immuonodeficiency virus (HIV) vaccine, with intramuscular DNA delivery by either Biojector 2000 needle-free injection system (Biojector) or CELLECTRA electroporation device. Methods. Healthy, HIV-uninfected adults were randomized to receive 4 mg of PENNVAX-G DNA delivered intramuscularly by Biojector or electroporation at baseline and week 4 followed by intramuscular injection of 108 plaque forming units of MVA-CMDR at weeks 12 and 24. The open-label part A was conducted in the United States, followed by a double-blind, placebo-controlled part B in East Africa. Solicited and unsolicited adverse events were recorded, and immune responses were measured. Results. Eighty-eight of 100 enrolled participants completed all study injections, which were generally safe and well tolerated, with more immediate, but transient, pain in the electroporation group. Cellular responses were observed in 57% of vaccine recipients tested and were CD4 predominant. High rates of binding antibody responses to CRF01-AE antigens, including gp70 V1V2 scaffold, were observed. Neutralizing antibodies were detected in a peripheral blood mononuclear cell assay, and moderate antibody-dependent, cell-mediated cytotoxicity activity was demonstrated. Discussion. The PVG/MVA-CMDR HIV-1 vaccine regimen is safe and immunogenic. Substantial differences in safety or immunogenicity between modes of DNA delivery were not observed.
AB - Background. We report the first-in-human safety and immunogenicity evaluation of PENNVAX-G DNA/modified vaccinia Ankara-Chiang Mai double recombinant (MVA-CMDR) prime-boost human immuonodeficiency virus (HIV) vaccine, with intramuscular DNA delivery by either Biojector 2000 needle-free injection system (Biojector) or CELLECTRA electroporation device. Methods. Healthy, HIV-uninfected adults were randomized to receive 4 mg of PENNVAX-G DNA delivered intramuscularly by Biojector or electroporation at baseline and week 4 followed by intramuscular injection of 108 plaque forming units of MVA-CMDR at weeks 12 and 24. The open-label part A was conducted in the United States, followed by a double-blind, placebo-controlled part B in East Africa. Solicited and unsolicited adverse events were recorded, and immune responses were measured. Results. Eighty-eight of 100 enrolled participants completed all study injections, which were generally safe and well tolerated, with more immediate, but transient, pain in the electroporation group. Cellular responses were observed in 57% of vaccine recipients tested and were CD4 predominant. High rates of binding antibody responses to CRF01-AE antigens, including gp70 V1V2 scaffold, were observed. Neutralizing antibodies were detected in a peripheral blood mononuclear cell assay, and moderate antibody-dependent, cell-mediated cytotoxicity activity was demonstrated. Discussion. The PVG/MVA-CMDR HIV-1 vaccine regimen is safe and immunogenic. Substantial differences in safety or immunogenicity between modes of DNA delivery were not observed.
KW - Electroporation
KW - HIV vaccine
KW - Modified vaccinia Ankara
KW - Needle-free injection
UR - http://www.scopus.com/inward/record.url?scp=85038226020&partnerID=8YFLogxK
U2 - 10.1093/infdis/jix456
DO - 10.1093/infdis/jix456
M3 - Article
C2 - 28968759
AN - SCOPUS:85038226020
SN - 0022-1899
VL - 216
SP - 1080
EP - 1090
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 9
ER -