Boosting of HIV-1 neutralizing antibody responses by a distally related retroviral envelope protein.
Our knowledge of the binding sites for neutralizing Abs (NAb) that recognize a broad range of HIV-1 strains (bNAb) has substantially increased in recent years. However, gaps remain in our understanding of how to focus B cell responses to vulnerable conserved sites within the HIV-1 envelope glycoprotein (Env). In this article, we report an immunization strategy composed of a trivalent HIV-1 (clade B envs) DNA prime, followed by a SIVmac239 gp140 Env protein boost that aimed to focus the immune response to structurally conserved parts of the HIV-1 and simian immunodeficiency virus (SIV) Envs. Heterologous NAb titers, primarily to tier 1 HIV-1 isolates, elicited during the trivalent HIV-1 env prime, were significantly increased by the SIVmac239 gp140 protein boost in rabbits. Epitope mapping of Ab-binding reactivity revealed preferential recognition of the C1, C2, V2, V3, and V5 regions. These results provide a proof of concept that a distally related retroviral SIV Env protein boost can increase pre-existing NAb responses against HIV-1.
Science for Life Laboratory, Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, S-14186 Stockholm, Sweden;
Hannes
H
Uchtenhagen
The Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom;
Torben
T
Schiffner
Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, United Kingdom;
Emma
E
Bowles
Virology Unit, Biomedical Department, Institute of Tropical Medicine, 2000 Antwerpen, Belgium;
Leo
L
Heyndrickx
Department of Surgery, Duke University Medical Center, Durham, NC 27710;
Celia
C
LaBranche
Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, S-14186 Stockholm, Sweden;
Steven E
SE
Applequist
Department of Laboratory Medicine, Lund University, S-22362 Lund, Sweden;
Marianne
M
Jansson
Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, United Kingdom;
Thushan
T
De Silva
Pepscan Therapeutics, 8243RC Lelystad, The Netherlands;
Jaap Willem
JW
Back
Science for Life Laboratory, Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, S-14186 Stockholm, Sweden;
Adnane
A
Achour
Viral Evolution and Transmission Unit, Division of Immunology, Transplant and Infectious Diseases, San Raffaele Scientific Institute, 20132 Milan, Italy;
Gabriella
G
Scarlatti
Department of Virology, Statens Serum Institut, DK-2300 Copenhagen, Denmark; and Institute of Clinical Research, University of Southern Denmark, DK-5000 Odense, Denmark.
Anders
A
Fomsgaard
Department of Surgery, Duke University Medical Center, Durham, NC 27710;
David
D
Montefiori
Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, United Kingdom;
Guillaume
G
Stewart-Jones
Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, S-14186 Stockholm, Sweden; anna-lena.spetz@su.se.
Anna-Lena
AL
Spetz
D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D001483:Base Sequence; D005260:Female; D015483:HIV Antibodies / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary; D008297:Male; D008969:Molecular Sequence Data; D011817:Rabbits; D012191:Retroviridae Proteins / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology
D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D012191:Retroviridae Proteins; C080347:SIV envelope protein gp110; D014759:Viral Envelope Proteins; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1