Assessment of antibody responses against gp41 in HIV-1-infected patients using soluble gp41 fusion proteins and peptides derived from M group consensus envelope.
Human immunodeficiency virus type 1 (HIV-1) transmembrane glycoprotein gp41 is targeted by broadly-reactive neutralizing antibodies 2F5 and 4E10, making it an attractive target for vaccine development. To better assess immunogenic properties of gp41, we generated five soluble glutathione S-transferase fusion proteins encompassing C-terminal 30, 64, 100, 142, or 172 (full-length) amino acids of gp41 ectodomain from M group consensus envelope sequence. Antibody responses in HIV-1-infected patients were evaluated using these proteins and overlapping peptides. We found (i) antibody responses against different regions of gp41 varied tremendously among individual patients, (ii) patients with stronger antibody responses against membrane-proximal external region exhibit broader and more potent neutralizing activity, and (iii) several patients mounted antibodies against epitopes that are near, or overlap with, those targeted by 2F5 or 4E10. These soluble gp41 fusion proteins could be an important source of antigens for future vaccine development efforts.
Penn-Nicholson
Adam
A
Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Han
Dong P
DP
Kim
Soon J
SJ
Park
Hanna
H
Ansari
Rais
R
Montefiori
David C
DC
Cho
Michael W
MW
D000595:Amino Acid Sequence; D016384:Consensus Sequence; D000939:Epitopes; D015967:Gene Expression Regulation, Viral; D015483:HIV Antibodies / Q000276:immunology*; D015488:HIV Antigens / Q000737:chemistry / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D006801:Humans; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000276:immunology*; D012995:Solubility
D000939:Epitopes; D015483:HIV Antibodies; D015488:HIV Antigens; D015700:HIV Envelope Protein gp41; D011993:Recombinant Fusion Proteins; C514787:gp41 protein, Human immunodeficiency virus 1