PMID- 34099328
OWN - NLM
STAT- MEDLINE
DCOM- 20210628
LR  - 20231213
IS  - 1873-2518 (Electronic)
IS  - 0264-410X (Print)
IS  - 0264-410X (Linking)
VI  - 39
IP  - 29
DP  - 2021 Jun 29
TI  - Safety and immunogenicity of an HIV-1 gp120-CD4 chimeric subunit vaccine in a 
      phase 1a randomized controlled trial.
PG  - 3879-3891
LID - S0264-410X(21)00685-X [pii]
LID - 10.1016/j.vaccine.2021.05.090 [doi]
AB  - A major challenge for HIV vaccine development is to raise anti-envelope 
      antibodies capable of recognizing and neutralizing diverse strains of HIV-1. 
      Accordingly, a full length single chain (FLSC) of gp120-CD4 chimeric vaccine 
      construct was designed to present a highly conserved CD4-induced (CD4i) HIV-1 
      envelope structure that elicits cross-reactive anti-envelope humoral responses 
      and protective immunity in animal models of HIV infection. IHV01 is the FLSC 
      formulated in aluminum phosphate adjuvant. We enrolled 65 healthy adult 
      volunteers in this first-in-human phase 1a randomized, double-blind, 
      placebo-controlled study with three dose-escalating cohorts (75 microg, 150 microg, and 
      300 microg doses). Intramuscular injections were given on weeks 0, 4, 8, and 24. 
      Participants were followed for an additional 24 weeks after the last 
      immunization. The overall incidence of adverse events (AEs) was not significantly 
      different between vaccinees and controls. The majority (89%) of vaccine-related 
      AE were mild. The most common vaccine-related adverse event was injection site 
      pain. There were no vaccine-related serious AE, discontinuation due to AE, 
      intercurrent HIV infection, or significant decreases in CD4 count. By the final 
      vaccination, all vaccine recipients developed antibodies against IHV01 and 
      demonstrated anti-CD4i epitope antibodies. The elicited antibodies reacted with 
      CD4 non-liganded Env antigens from diverse HIV-1 strains. Antibody-dependent 
      cell-mediated cytotoxicity against heterologous infected cells or gp120 bound to 
      CD4+ cells was evident in all cohorts as were anti-gp120 T-cell responses. IHV01 
      vaccine was safe, well tolerated, and immunogenic at all doses tested. The 
      vaccine raised broadly reactive humoral responses against conserved CD4i epitopes 
      on gp120 that mediates antiviral functions.
CI  - Copyright (c) 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.
FAU - Chua, Joel V
AU  - Chua JV
AD  - Division of Clinical Care and Research, Institute of Human Virology, University 
      of Maryland School of Medicine, Baltimore, MD, USA.
FAU - Davis, Charles
AU  - Davis C
AD  - Division of Clinical Care and Research, Institute of Human Virology, University 
      of Maryland School of Medicine, Baltimore, MD, USA.
FAU - Husson, Jennifer S
AU  - Husson JS
AD  - Division of Clinical Care and Research, Institute of Human Virology, University 
      of Maryland School of Medicine, Baltimore, MD, USA.
FAU - Nelson, Amy
AU  - Nelson A
AD  - Division of Clinical Care and Research, Institute of Human Virology, University 
      of Maryland School of Medicine, Baltimore, MD, USA.
FAU - Prado, Ilia
AU  - Prado I
AD  - Division of Vaccine Research, Institute of Human Virology, University of Maryland 
      School of Medicine, Baltimore, MD, USA.
FAU - Flinko, Robin
AU  - Flinko R
AD  - Division of Vaccine Research, Institute of Human Virology, University of Maryland 
      School of Medicine, Baltimore, MD, USA.
FAU - Lam, Ka Wing J
AU  - Lam KWJ
AD  - Division of Clinical Care and Research, Institute of Human Virology, University 
      of Maryland School of Medicine, Baltimore, MD, USA.
FAU - Mutumbi, Lydiah
AU  - Mutumbi L
AD  - Division of Clinical Care and Research, Institute of Human Virology, University 
      of Maryland School of Medicine, Baltimore, MD, USA.
FAU - Mayer, Bryan T
AU  - Mayer BT
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 
      Seattle, WA, USA.
FAU - Dong, Dan
AU  - Dong D
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 
      Seattle, WA, USA.
FAU - Fulp, William
AU  - Fulp W
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 
      Seattle, WA, USA.
FAU - Mahoney, Celia
AU  - Mahoney C
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 
      Seattle, WA, USA.
FAU - Gerber, Monica
AU  - Gerber M
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 
      Seattle, WA, USA.
FAU - Gottardo, Raphael
AU  - Gottardo R
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 
      Seattle, WA, USA; Public Health Sciences Division, Fred Hutchinson Cancer 
      Research Center, Seattle, WA, USA.
FAU - Gilliam, Bruce L
AU  - Gilliam BL
AD  - Division of Clinical Care and Research, Institute of Human Virology, University 
      of Maryland School of Medicine, Baltimore, MD, USA.
FAU - Greene, Kelli
AU  - Greene K
AD  - Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, 
      USA.
FAU - Gao, Hongmei
AU  - Gao H
AD  - Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, 
      USA.
FAU - Yates, Nicole
AU  - Yates N
AD  - Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, 
      USA.
FAU - Ferrari, Guido
AU  - Ferrari G
AD  - Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, 
      USA.
FAU - Tomaras, Georgia
AU  - Tomaras G
AD  - Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, 
      USA.
FAU - Montefiori, David
AU  - Montefiori D
AD  - Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, 
      USA.
FAU - Schwartz, Jennifer A
AU  - Schwartz JA
AD  - Intralytix, Columbia, MD, USA.
FAU - Fouts, Timothy
AU  - Fouts T
AD  - Advanced BioScience Laboratories, Rockville, MD, USA.
FAU - DeVico, Anthony L
AU  - DeVico AL
AD  - Division of Vaccine Research, Institute of Human Virology, University of Maryland 
      School of Medicine, Baltimore, MD, USA; Global Virus Network, Baltimore, MD, USA.
FAU - Lewis, George K
AU  - Lewis GK
AD  - Division of Vaccine Research, Institute of Human Virology, University of Maryland 
      School of Medicine, Baltimore, MD, USA; Global Virus Network, Baltimore, MD, USA.
FAU - Gallo, Robert C
AU  - Gallo RC
AD  - Global Virus Network, Baltimore, MD, USA; Division of Basic Science, Institute of 
      Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.
FAU - Sajadi, Mohammad M
AU  - Sajadi MM
AD  - Division of Clinical Care and Research, Institute of Human Virology, University 
      of Maryland School of Medicine, Baltimore, MD, USA; Intralytix, Columbia, MD, 
      USA. Electronic address: msajadi@ihv.umaryland.edu.
LA  - eng
GR  - P01 AI124912/AI/NIAID NIH HHS/United States
GR  - R01 AI147870/AI/NIAID NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20210604
PL  - Netherlands
TA  - Vaccine
JT  - Vaccine
JID - 8406899
RN  - 0 (AIDS Vaccines)
RN  - 0 (CD4 Antigens)
RN  - 0 (HIV Antibodies)
RN  - 0 (HIV Envelope Protein gp120)
RN  - 0 (Vaccines, Subunit)
SB  - IM
MH  - AIDS Vaccines/adverse effects/*immunology
MH  - Adult
MH  - Animals
MH  - CD4 Antigens
MH  - HIV Antibodies
MH  - HIV Envelope Protein gp120
MH  - *HIV Infections/prevention & control
MH  - HIV-1
MH  - Humans
MH  - *Immunogenicity, Vaccine
MH  - Vaccines, Subunit/adverse effects/immunology
PMC - PMC8224181
OTO - NOTNLM
OT  - CD4i
OT  - Chimeric subunit vaccine
OT  - Full-length single chain (FLSC)
OT  - HIV
OT  - Vaccine
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2021/06/09 06:00
MHDA- 2021/06/29 06:00
PMCR- 2021/06/29
CRDT- 2021/06/08 05:51
PHST- 2021/01/28 00:00 [received]
PHST- 2021/04/14 00:00 [revised]
PHST- 2021/05/23 00:00 [accepted]
PHST- 2021/06/09 06:00 [pubmed]
PHST- 2021/06/29 06:00 [medline]
PHST- 2021/06/08 05:51 [entrez]
PHST- 2021/06/29 00:00 [pmc-release]
AID - S0264-410X(21)00685-X [pii]
AID - 10.1016/j.vaccine.2021.05.090 [doi]
PST - ppublish
SO  - Vaccine. 2021 Jun 29;39(29):3879-3891. doi: 10.1016/j.vaccine.2021.05.090. Epub 
      2021 Jun 4.