Cellular and humoral responses to an HIV DNA prime by electroporation boosted with recombinant vesicular stomatitis virus expressing HIV subtype C Env in a randomized controlled clinical trial.

Autor: Wilson GJ; Vanderbilt University Medical Center, Nashville, TN, United States., Rodriguez B; Case Western Reserve University, Cleveland, OH, United States., Li SS; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, United States., Allen M; DAIDS/NIAID/NIH, Rockville, MD, United States., Frank I; University of Pennsylvania, Philadelphia, PA, United States., Rudnicki E; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, United States., Trahey M; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, United States., Kalams S; Vanderbilt University Medical Center, Nashville, TN, United States., Hannaman D; Ichor Medical Systems, San Diego, CA, United States., Clarke DK; Auro Vaccines LLC (formerly Profectus Biosciences, Inc.), Pearl River, NY, United States., Xu R; Auro Vaccines LLC (formerly Profectus Biosciences, Inc.), Pearl River, NY, United States., Egan M; Auro Vaccines LLC (formerly Profectus Biosciences, Inc.), Pearl River, NY, United States., Eldridge J; Auro Vaccines LLC (formerly Profectus Biosciences, Inc.), Pearl River, NY, United States., Pensiero M; DAIDS/NIAID/NIH, Rockville, MD, United States., Latham T; Auro Vaccines LLC (formerly Profectus Biosciences, Inc.), Pearl River, NY, United States., Ferrari G; Department of Surgery, Duke University, Durham, NC, United States., Montefiori DC; Department of Surgery, Duke University, Durham, NC, United States., Tomaras GD; Department of Surgery, Duke University, Durham, NC, United States., De Rosa SC; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, United States., Jacobson JM; Case Western Reserve University, Cleveland, OH, United States., Miner MD; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, United States., Elizaga M; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, United States.
Jazyk: angličtina
Zdroj: Vaccine [Vaccine] 2023 Apr 17; Vol. 41 (16), pp. 2696-2706. Date of Electronic Publication: 2023 Mar 17.
DOI: 10.1016/j.vaccine.2023.03.015
Abstrakt: Background: HIV subtypes B and C together account for around 60% of HIV-1 cases worldwide. We evaluated the safety and immunogenicity of a subtype B DNA vaccine prime followed by a subtype C viral vector boost.
Methods: Fourteen healthy adults received DNA plasmid encoding HIV-1 subtype B nef/tat/vif and env (n = 11) or placebo (n = 3) intramuscularly (IM) via electroporation (EP) at 0, 1, and 3 months, followed by IM injection of recombinant vesicular stomatitis virus encoding subtype C Env or placebo at 6 and 9 months. Participants were assessed for safety, tolerability of EP, and Env-specific T-cell and antibody responses.
Results: EP was generally well tolerated, although some device-related adverse events did occur, and vaccine reactogenicity was mild to moderate. The vaccine stimulated Env-specific CD4 + T-cell responses in greater than 80% of recipients, and CD8 + T-cell responses in 30%. Subtype C Env-specific IgG binding antibodies (bAb) were elicited in all vaccine recipients, and antibody-dependent cell-mediated cytotoxicity (ADCC) responses to vaccine-matched subtype C targets in 80%. Negligible V1/V2 and neutralizing antibody (nAb) responses were detected.
Conclusions: This prime/boost regimen was safe and tolerable, with some device-related events, and immunogenic. Although immunogenicity missed targets for an HIV vaccine, the DNA/rVSV platform may be useful for other applications.
Clinicaltrials: gov: NCT02654080.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The following authors declare no conflicts of interest: MT, MDM, JE, DCM, JMJ, ME, DKC, GJW, GDT, GF, SK, ER, ME, TL, RX, SL. MA and MP are employed by NIAID but had no role in the funding decisions or grant oversight. DH is a full-time employee of Ichor Medical Systems, Inc. and receives a salary and equity for this work. SCDR reports funding from NIH, Bill & Melinda Gates Foundation for the work. IF gets research support from Moderna, Janssen, Pfizer and Sanofi, and is a consultant for Gilead, GlaxoSmithKline and Merck.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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