Bovine papillomavirus-like particles presenting conserved epitopes from membrane-proximal external region of HIV-1 gp41 induced mucosal and systemic antibodies.
Two conserved epitopes, located in the membrane-proximal external region (MPER) of the human immunodeficiency virus type 1 (HIV-1) gp41, are recognized by two HIV-1 broadly neutralizing antibodies 2F5 and 4E10, and are promising targets for vaccine design in efforts to elicit anti-HIV-1 broadly neutralizing antibodies. Since most HIV-1 infections initiate at mucosal surfaces, induction of mucosal neutralizing antibodies is necessary and of utmost importance to counteract HIV-1 infection. Here, we utilized a mucosal vaccine vector, bovine papillomavirus (BPV) virus-like particles (VLPs), as a platform to present HIV-1 neutralizing epitopes by inserting the extended 2F5 or 4E10 epitope or the MPER domain into D-E loop of BPV L1 respectively. The chimeric VLPs presenting MPER domain resembled the HIV-1 natural epitopes better than the chimeric VLPs presenting single epitopes. Oral immunization of mice with the chimeric VLPs displaying the 2F5 epitope or MPER domain elicited epitope-specific serum IgGs and mucosal secretory IgAs. The induced antibodies specifically recognized the native conformation of MPER in the context of HIV-1 envelope protein. The antibodies induced by chimeric VLPs presenting MPER domain are able to partially neutralize HIV-1 viruses from clade B and clade C.
Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, United States.
Yougang
Y
Zhai
Zhenyu
Z
Zhong
Mohammadreza
M
Zariffard
Gregory T
GT
Spear
Liang
L
Qiao
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000284:Administration, Oral; D000818:Animals; D002417:Cattle; D004337:Drug Carriers; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D005260:Female; D015483:HIV Antibodies / Q000032:analysis* / Q000097:blood*; D015700:HIV Envelope Protein gp41 / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D018928:Immunity, Mucosal; D007071:Immunoglobulin A, Secretory / Q000032:analysis / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D027383:Papillomaviridae / Q000235:genetics; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
D016915:AIDS Vaccines; D004337:Drug Carriers; D000939:Epitopes; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D014614:Vaccines, Synthetic; D058425:Vaccines, Virus-Like Particle; C514787:gp41 protein, Human immunodeficiency virus 1
Bovine papillomavirus-like particle; HIV-1; Membrane-proximal external region; Mucosal; Neutralizing antibody; Vaccine